uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
12 1 - 50 av 62
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Bergman, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Brandt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Nordeman, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation2017Ingår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 10, artikel-id 1688Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [C-11] carbon monoxide. Starting with amines and [C-11] carbon monoxide, both symmetrical and unsymmetrical C-11-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [C-11] carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/mu mol-319 GBq/mu mol). DFT calculations were found to support a reaction mechanism proceeding through an C-11-labelled isocyanate intermediate.

  • 2. Bogdanović, Renée Marie
    et al.
    Syvänen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Michler, Christina
    Russmann, Vera
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Windhorst, Albert D
    Lammertsma, Adriaan A
    de Lange, Elisabeth C
    Voskuyl, Rob A
    Potschka, Heidrun
    (R)-[(11)C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: Evaluation in a rat epilepsy model2014Ingår i: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 85, s. 104-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[(11)C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[(11)C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.

  • 3. Chiotis, Konstantinos
    et al.
    Saint-Aubert, Laure
    Savitcheva, Irina
    Jelic, Vesna
    Andersen, Pia
    Jonasson, My
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Almkvist, Ove
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Nordberg, Agneta
    Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm2016Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, nr 9, s. 1686-1699Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [(18)F]THK5317 (also known as (S)-[(18)F]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.

    METHODS: Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [(18)F]THK5317, [(11)C] Pittsburgh compound B ([(11)C]PIB), and [(18)F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [(11)C]PIB-positive (n = 11) and MCI [(11)C]PIB-negative (n = 2) groups.

    RESULTS: Test-retest variability for [(18)F]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [(11)C]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [(18)F]THK5317 retention than healthy controls (p = 0.002 and p = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [(18)F]THK5317 retention and [(18)F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [(18)F]THK5317 and [(11)C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [(11)C]PIB but high [(18)F]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients.

    CONCLUSIONS: The tau-specific PET tracer [(18)F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.

  • 4.
    Chow, Shiao Y.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Low-Pressure Radical C-11-Aminocarbonylation of Alkyl Iodides through Thermal Initiation2016Ingår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, nr 36, s. 5980-5989Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A radical C-11-aminocarbonylation protocol characterized by excellent substrate compatibility was developed to transform alkyl iodides into C-11-labelled amides, including the 11-HSD1 inhibitor [carbonyl-C-11]adamantan-1-yl(piperidin-1-yl)methanone. This protocol serves as a complementary extension of palladium-mediated C-11-aminocarbonylation, which is limited to the preparation of C-11-labelled compounds lacking beta-hydrogen atoms. The use of AIBN as a radical initiator and a low-pressure xenon-[C-11]CO delivery unit represents a simple and convenient alternative to previous radical C-11-carbonylation methodologies burdened with the need for a proprietary high pressure reactor connected to a light source.

  • 5.
    Eriksson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Synthesis of 11C-labelled Alkyl Iodides: Using Non-thermal Plasma and Palladium-mediated Carbonylation Methods2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Compounds labelled with 11C (β+, t1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects.

    The feasibility of preparing [11C]methyl iodide from [11C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [11C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [11C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact.

    Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [11C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-11C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-11C]Propyl iodide and [1-11C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-11C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [11C]carbon monoxide. [1-11C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-11C]butyl iodide with 146 GBq/mmol from 8 GBq.

    Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-11C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield N-[carbonyl-11C]benzylacrylamide. In an alternative method, [carbonyl-11C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [11C]carbon monoxide, N-[carbonyl-11C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol.

    Delarbeten
    1. [C-11]methyl iodide from [C-11]methane and iodine using a non-thermal plasma method
    Öppna denna publikation i ny flik eller fönster >>[C-11]methyl iodide from [C-11]methane and iodine using a non-thermal plasma method
    2006 (Engelska)Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, nr 13, s. 1177-1186Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A method and an apparatus for preparing [C-11]methyl iodide from [C-11]methane and iodine in a single pass through a non-thermal plasma reactor has been developed. The plasma was created by applying high voltage (400 V/31 kHz) to electrodes in a stream of helium gas at reduced pressure. The [C-11]methane used in the experiments was produced from [C-11]carbon dioxide via reduction with hydrogen over nickel. [C-11]methyl iodide was obtained with a specific radioactivity of 412 +/- 32 GBq/mu mol within 6 min from approximately 24 GBq of [C-11]carbon dioxide. The decay corrected radiochemical yield was 13 +/- 3% based on [C-11]carbon dioxide at start of synthesis. [C-11]Flumazenil was synthesized via a N-alkylation with the prepared [C-11]methyl iodide.

    Nyckelord
    [C-11]methyl iodide, [C-11]methane, non-thermal plasma, specific radioactivity
    Nationell ämneskategori
    Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-94929 (URN)10.1002/jlcr.1135 (DOI)000242796700006 ()
    Tillgänglig från: 2006-10-05 Skapad: 2006-10-05 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    2. Synthesis of [1-11C]ethyl iodide from carbon monoxide and its application in alkylation reactions
    Öppna denna publikation i ny flik eller fönster >>Synthesis of [1-11C]ethyl iodide from carbon monoxide and its application in alkylation reactions
    2004 (Engelska)Ingår i: Journal of Labelled Compounds and Radiopharmaceuticals, ISSN 0362-4803, Vol. 47, nr 11, s. 723-731Artikel i tidskrift (Refereegranskat) Published
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-94930 (URN)
    Tillgänglig från: 2006-10-05 Skapad: 2006-10-05 Senast uppdaterad: 2015-09-24
    3. Synthesis of [1-C-11]propyl and [1-C-11]butyl iodide from [C-11]carbon monoxide and their use in alkylation reactions
    Öppna denna publikation i ny flik eller fönster >>Synthesis of [1-C-11]propyl and [1-C-11]butyl iodide from [C-11]carbon monoxide and their use in alkylation reactions
    2006 (Engelska)Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, nr 12, s. 1105-1116Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A method to prepare [1-C-11]propyl iodide and [1-C-11]butyl iodide from [C-11]carbon monoxide via a three step reaction sequence is presented. Palladium mediated formylation of ethene with [C-11]carbon monoxide and hydrogen gave [1-C-11]propionaldehyde and [1-C-11]propionic acid. The carbonylation products were reduced and subsequently converted to [1-C-11]propyl iodide. Labelled propyl iodide was obtained in 58 +/- 4% decay corrected radiochemical yield and with a specific radioactivity of 270 +/- 33 GBq/mu mol within 15 min from approximately 12 GBq of [C-11]carbon monoxide. The position of the label was confirmed by C-13-labelling and C-13-NMR analysis. [1-C-11]Butyl iodide was obtained correspondingly from propene and approximately 8 GBq of [C-11]carbon monoxide, in 34 +/- 2% decay corrected radiochemical yield and with a specific radioactivity of 146 +/- 20 GBq/mu mol. The alkyl iodides were used in model reactions to synthesize [O-propyl-1-C-11]propyl and [O-butyl-1-C-11]butyl benzoate. Propyl and butyl analogues of etomidate, a (beta-11-hydroxylase inhibitor, were also synthesized.

    Nyckelord
    [C-11]carbon monoxide, [1-C-11]propyl iodide, [1-C-11]butyl iodide, carbonylation, formylation, alkylation
    Nationell ämneskategori
    Kemi
    Identifikatorer
    urn:nbn:se:uu:diva-94931 (URN)10.1002/jlcr.1119 (DOI)000242335900009 ()
    Tillgänglig från: 2006-10-05 Skapad: 2006-10-05 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    4. Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation
    Öppna denna publikation i ny flik eller fönster >>Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation
    2007 (Engelska)Ingår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, nr 3, s. 455-461Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Two methods are presented for the synthesis of acrylamides labelled with C-11 (beta(+), t(1/2) = 20.4 min) and C-11 in the carbonyl position. In the first method, [1-C-11]acrylic acid is synthesised from [C-11]carbon monoxide by palladium-mediated hydroxy-carbonylation of acetylene. The labelled carboxylic acid is converted into the acyl chloride and subsequently treated with amine to yield N-benzyl[carbonyl(11)C]acrylamide, The second method utilizes [C-11]carbon monoxide in a palladium-mediated carbonylative cross-coupling of vinyl halides and amines. A higher radiochemical yield is achieved with the latter method and the amount of amine needed is decreased to 1/20. The C-11-labelled acrylamides were isolated in up to 81 % decay-corrected radiochemical yield. Starting from 10 +/- 0.5GBq of [C-11]carbon monoxide, N-benzyl[carbonyl-C-11]acrylamide was obtained in 4 min with a specific radioactivity of 330 +/- 4 GBq mu mol-(1). Co-labelling with C-11 and C-13 enabled confirmation of the labelled position by C-13 NMR spectroscopy.

    Nyckelord
    Carbonylation, Amides, Carbon monoxide, Isotopic labelling, Carbon-11, 11C, PET
    Nationell ämneskategori
    Kemi
    Forskningsämne
    Organisk kemi
    Identifikatorer
    urn:nbn:se:uu:diva-98592 (URN)10.1002/ejoc.200600700 (DOI)000243600100007 ()
    Tillgänglig från: 2009-02-27 Skapad: 2009-02-27 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    5. [1-11C]Ethyl iodide and [1-11C]propyl iodide in the synthesis of two potential NK1-receptor ligands and initial PET-imaging
    Öppna denna publikation i ny flik eller fönster >>[1-11C]Ethyl iodide and [1-11C]propyl iodide in the synthesis of two potential NK1-receptor ligands and initial PET-imaging
    Visa övriga...
    (Engelska)Manuskript (Övrigt vetenskapligt)
    Nationell ämneskategori
    Läkemedelskemi
    Identifikatorer
    urn:nbn:se:uu:diva-94933 (URN)
    Tillgänglig från: 2006-10-05 Skapad: 2006-10-05 Senast uppdaterad: 2018-01-13
  • 6.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Single valve module for production and efficient transfer of [C-11]carbon monoxide to a disposable reaction vial2015Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 58, s. S303-S303Artikel i tidskrift (Övrigt vetenskapligt)
  • 7.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Antoni, Gunnar
    Långström, Bengt
    Synthesis of [1-11C]ethyl iodide from carbon monoxide and its application in alkylation reactions2004Ingår i: Journal of Labelled Compounds and Radiopharmaceuticals, ISSN 0362-4803, Vol. 47, nr 11, s. 723-731Artikel i tidskrift (Refereegranskat)
  • 8.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Antoni, Gunnar
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Synthesis of [1-C-11]propyl and [1-C-11]butyl iodide from [C-11]carbon monoxide and their use in alkylation reactions2006Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, nr 12, s. 1105-1116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A method to prepare [1-C-11]propyl iodide and [1-C-11]butyl iodide from [C-11]carbon monoxide via a three step reaction sequence is presented. Palladium mediated formylation of ethene with [C-11]carbon monoxide and hydrogen gave [1-C-11]propionaldehyde and [1-C-11]propionic acid. The carbonylation products were reduced and subsequently converted to [1-C-11]propyl iodide. Labelled propyl iodide was obtained in 58 +/- 4% decay corrected radiochemical yield and with a specific radioactivity of 270 +/- 33 GBq/mu mol within 15 min from approximately 12 GBq of [C-11]carbon monoxide. The position of the label was confirmed by C-13-labelling and C-13-NMR analysis. [1-C-11]Butyl iodide was obtained correspondingly from propene and approximately 8 GBq of [C-11]carbon monoxide, in 34 +/- 2% decay corrected radiochemical yield and with a specific radioactivity of 146 +/- 20 GBq/mu mol. The alkyl iodides were used in model reactions to synthesize [O-propyl-1-C-11]propyl and [O-butyl-1-C-11]butyl benzoate. Propyl and butyl analogues of etomidate, a (beta-11-hydroxylase inhibitor, were also synthesized.

  • 9.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Fang, Xiaotian T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hultqvist, Greta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Olberg, D. E.
    Univ Oslo, Dept Pharm, Oslo, Norway.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sehlin, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Syvänen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    [F-18]Tetrazine-trans-cyclooctene mediated labelling of antibodies for PET imaging of amyloid-beta2018Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, s. S643-S643Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Roy, Tamal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Sawadjoon, Supaporn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Bachmann, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Sköld, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Selvaraju, Ram
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi.
    Eriksson, Olof
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Synthesis and initial preclinical evaluation of the CRTH2 antagonist [C-11] MK-72462019Ingår i: Journal of Labelled Compounds and Pharmaceuticals, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA , 2019, Vol. 62, s. S544-S545Konferensbidrag (Refereegranskat)
  • 11.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Roy, Tamal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Sawadjoon, Supaporn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Bachmann, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Sköld, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Larhed, Mats
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Weis, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Selvaraju, Ramkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass2019Ingår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 71, s. 1-10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: MK-7246 is a potent and selective antagonist for chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Within the pancreas CRTH2 is selectively expressed in pancreatic β-cells where it is believed to play a role in insulin release. Reduction in β-cell mass and insufficient insulin secretion in response to elevated blood glucose levels is a hallmark for type 1 and type 2 diabetes. Reported here is the synthesis of [11C]MK-7246 and initial preclinical evaluation towards CRTH2 imaging. The aim is to develop a method to quantify β-cell mass with PET and facilitate non-invasive studies of disease progression in individuals with type 2 diabetes.

    Methods: The precursor N-desmethyl-O-methyl MK-7246 was synthesized in seven steps and subjected to methylation with [11C]methyl iodide followed by hydrolysis to obtain [11C]MK-7246 labelled in the N-methyl position. Preclinical evaluation included in vitro radiography and immune-staining performed in human pancreatic biopsies. Biodistribution studies were performed in rat by PET-MRI and in pig by PET-CT imaging. The specific tracer uptake was examined in pig by scanning before and after administration of MK-7246 (1 mg/kg). Predicted dosimetry of [11C]MK-7246 in human males was estimated based on the biodistribution in rat.

    Results: [11C]MK-7246 was obtained with activities sufficient for the current investigations (270±120 MBq) and a radiochemical purity of 93±2%. The tracer displayed focal binding in areas with insulin positive islet of Langerhans in human pancreas sections. Baseline uptake in pig was significantly reduced in CRTH2-rich areas after administration of MK-7246; pancreas (66% reduction) and spleen (88% reduction). [11C]MK-7246 exhibited a safe human predicted dosimetry profile as extrapolated from the rat biodistribution data.

    Conclusions: Initial preclinical in vitro and in vivo evaluation of [11C]MK-7246 show binding and biodistribution properties suitable for PET imaging of CRTH2. Further studies are warranted to assess its potential in β-cell mass imaging and CRTH2 drug development.

  • 12.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Thibblin, Alf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Verbeek, Joost
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Windhorst, Albert D.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    GMP compliant synthesis of [C-11]phenytoin by rhodium mediated [C-11]carbon monoxide carbonylation performed in disposable glass vials2015Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 58, s. S338-S338Artikel i tidskrift (Övrigt vetenskapligt)
  • 13.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Ulin, Johan
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    [C-11]methyl iodide from [C-11]methane and iodine using a non-thermal plasma method2006Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 49, nr 13, s. 1177-1186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A method and an apparatus for preparing [C-11]methyl iodide from [C-11]methane and iodine in a single pass through a non-thermal plasma reactor has been developed. The plasma was created by applying high voltage (400 V/31 kHz) to electrodes in a stream of helium gas at reduced pressure. The [C-11]methane used in the experiments was produced from [C-11]carbon dioxide via reduction with hydrogen over nickel. [C-11]methyl iodide was obtained with a specific radioactivity of 412 +/- 32 GBq/mu mol within 6 min from approximately 24 GBq of [C-11]carbon dioxide. The decay corrected radiochemical yield was 13 +/- 3% based on [C-11]carbon dioxide at start of synthesis. [C-11]Flumazenil was synthesized via a N-alkylation with the prepared [C-11]methyl iodide.

  • 14.
    Eriksson, Jonas
    et al.
    VU University Medical Center Amsterdam.
    van den Hoek, Johan
    Windhorst, Albert D.
    Transition metal mediated synthesis using [11C]CO at low pressure - a simplified method for 11C-carbonylation2012Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 55, s. 223-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transition metal mediated carbonylation with [11C]CO has proven a useful method to label a wide array of compounds in the carbonyl position. However, the general use in radiopharmaceutical synthesis has been hampered by the low solubility of carbon monoxide in most solvents and the resulting challenge to confine [11C]CO in low volume reaction vessels. This paper introduces a method that utilises xenon to transfer pre-concentrated [11C]CO to a sealed disposable glass vial containing carbonylation reagents. The high solubility of xenon in the organic solvent made it possible to confine the [11C]CO without utilising a pressure autoclave or chemical trapping additives. The utility of the method in 11C-carbonylation was investigated by conducting three model reactions, where [11C-carbonyl]N-benzylbenzamide, [11C-carbonyl]triclocarban and [11C-carbonyl]methyl nicotinate were afforded in decay corrected radiochemical yields of 71?+/-?6%, 42?+/-?15% and 29?+/-?10%, respectively. These promising results and the straight forward technical implementation suggest that 11C-cabonylation can become a viable mean to provide labelled carbonyl functionalities in routine radiopharmaceutical synthesis. Compounds labelled with short lived positron emitters are used in Positron Emission Tomography, a molecular imaging technology with applications in clinical diagnostics, clinical research and basic biomedical research.

  • 15.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Van Kooij, Rolph
    Schuit, Robert C.
    Froklage, Femke E.
    Reijneveld, Jaap C.
    Hendrikse, N. Harry
    Windhorst, Albert D.
    Synthesis of [3-N-11C-methyl]temozolomide via in situ activation of 3-N-hydroxymethyl temozolomide and alkylation with [11C]methyl iodide2015Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 58, nr 3, s. 122-126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Temozolomide is a chemotherapeutic drug that is mainly used in the treatment of primary glioblastoma multiforme and recurrent high-grade glioma. Here, we report an efficient good manufacturing practice compliant method for the synthesis of [3-N-11C-methyl]temozolomide from 3-N-hydroxymethyl temozolomide that cleaves off formaldehyde in situ and becomes activated towards alkylation with [11C]methyl iodide. The labelling method was developed for an on-going patient study in which the predictive value of [3-N-11C-methyl]temozolomide and positron emission tomography on the outcome of temozolomide treatment is being investigated. The precursor was reacted with [11C]methyl iodide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene in acetonitrile, heated at stepwise increasing temperature. Purification by semipreparative HPLC with pharmaceutical grade eluent and filtration gave approximately 10 mL sterile product solution ready for injection containing 1.55 ± 0.38 GBq (n = 5), the specific activity was 88 ± 25 GBq/μmol and the radiochemical purity was 98.5 ± 1.9%.13C-NMR spectroscopy confirmed the labelled position after colabelling with 11C and 13C.

  • 16.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Åberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Automation of the 'xenon method' and comparative study on C-11-carbonylation at ambient pressure versus high solvent pressure2013Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 56, nr S1, s. S96-S96Artikel i tidskrift (Övrigt vetenskapligt)
  • 17.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Åberg, Ola
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation2007Ingår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, nr 3, s. 455-461Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two methods are presented for the synthesis of acrylamides labelled with C-11 (beta(+), t(1/2) = 20.4 min) and C-11 in the carbonyl position. In the first method, [1-C-11]acrylic acid is synthesised from [C-11]carbon monoxide by palladium-mediated hydroxy-carbonylation of acetylene. The labelled carboxylic acid is converted into the acyl chloride and subsequently treated with amine to yield N-benzyl[carbonyl(11)C]acrylamide, The second method utilizes [C-11]carbon monoxide in a palladium-mediated carbonylative cross-coupling of vinyl halides and amines. A higher radiochemical yield is achieved with the latter method and the amount of amine needed is decreased to 1/20. The C-11-labelled acrylamides were isolated in up to 81 % decay-corrected radiochemical yield. Starting from 10 +/- 0.5GBq of [C-11]carbon monoxide, N-benzyl[carbonyl-C-11]acrylamide was obtained in 4 min with a specific radioactivity of 330 +/- 4 GBq mu mol-(1). Co-labelling with C-11 and C-13 enabled confirmation of the labelled position by C-13 NMR spectroscopy.

  • 18.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Åberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Selvaraju, Ram K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Strategy to develop a MAO-A-resistant 5-hydroxy-L-[beta-C-11]tryptophan isotopologue based on deuterium kinetic isotope effects2014Ingår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, nr 1, artikel-id 62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The serotonin precursor 5-hydroxy-L-[β-11C]tryptophan ([11C]HTP) is in clinical use for localization of neuroendocrine tumors and has been suggested as a proxy marker for pancreatic islet cells. However, degradation by monoamine oxidase-A (MAO-A) reduces retention and the contrast to non-endocrine tissue.

    Methods

    A synthesis method was developed for 5-hydroxy-L-[β-11C2H]tryptophan ([11C]DHTP), an isotopologue of [11C]HTP, labeled with 11C and 2H at the β-position adjacent to the carbon involved in MAO-A decarboxylation. MAO-A-mediated degradation of [11C]DHTP was evaluated and compared to non-deuterated [11C]HTP.

    Results

    [11C]DHTP was synthesized with a radiochemical purity of >98%, radioactivity of 620 ± 190 MBq, and deuterium (2H or 2H2) incorporation at the β-position of 22% ±5%. Retention and resistance to MAO-A-mediated degradation of [11C]DHTP were increased in cells but not in non-human primate pancreas.

    Conclusions

    Partial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.

  • 19.
    Fang, Xiaotian T.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. PET Centre, Uppsala University Hospital, 751 85 Uppsala, Sweden.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala University Hospital, 751 85 Uppsala, SwedenUppsala University Hospital, 751 85 Uppsala, Sweden.
    Yngve, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala University Hospital, 751 85 Uppsala, SwedenUppsala University Hospital, 751 85 Uppsala, Sweden.
    Cato, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sehlin, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Syvänen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [(11)C]ABP688 PET imaging and ex vivo immunoblotting2017Ingår i: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 113, nr Pt A, s. 293-300, artikel-id S0028-3908(16)30459-2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) into insoluble plaques. Intermediates, Aβ oligomers (Aβo), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [(11)C]PIB, binds and visualizes Aβ plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. Aβo alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning. In order to convey these neurotoxic effects, Aβo requires interaction with the metabotropic glutamate 5 receptor (mGluR5). The aim was to investigate in vivo mGluR5 changes in an Aβ pathology model using PET. Wild type C57/BL6 (wt) and AβPP transgenic mice (tg-ArcSwe), 4, 8, and 16 months old, were PET scanned with [(11)C]ABP688, which is highly specific to mGluR5, to investigate changes in mGluR5. Mouse brains were extracted postscan and mGluR5 and Aβ protofibril levels were assessed with immunoblotting and ELISA respectively. Receptor-dense brain regions (hippocampus, thalamus, and striatum) displayed higher [(11)C]ABP688 concentrations corresponding to mGluR5 expression pattern. Mice had similar uptake levels of [(11)C]ABP688 regardless of genotype or age. Immunoblotting revealed general decline in mGluR5 expression and elevated levels of mGluR5 in 16 months old tg-ArcSwe compared with wt mice. [(11)C]ABP688 could visualize mGluR5 in the mouse brain. In conclusion, mGluR5 levels were found to decrease with age and tended to be higher in tg-ArcSwe compared with wt mice, however these changes could not be quantified with PET.

  • 20. Fang, Yao-ren
    et al.
    Gao, Ying
    Ryberg, Per
    Eriksson, Jonas
    Department of Organic Chemistry, Institute of Chemistry.
    Kolodziejska-Huben, Magdalena
    Dybala-Defratyka, Agnieszka
    Madhavan, S
    Danielsson, Rolf
    Paneth, Piotr
    Matsson, Olle
    Westaway, Kenneht Charles
    Experimental and Theoretical Multiple Kinetic Isotope Effects for an SN2 Reaction. An Attempt to Determine Transition-State Structure and the Ability of Theoretical Methods to Predict Experimental Kinetic Isotope Effects2003Ingår i: Chemistry European Journal, nr 9, s. 2696-2709Artikel i tidskrift (Refereegranskat)
  • 21. Fang, Yao-ren
    et al.
    MacMillar, Susanna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi, Organisk kemi II.
    Eriksson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Kolodziejska-Huben, Magdalena
    Dybala-Defratyka, Agnieszka
    Paneth, Piotr
    Matsson, Olle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi, Organisk kemi II.
    Westaway, Kenneth Charles
    The Effect of Solvent on the Structure of the Transition State for the SN2 Reaction between Cyanide Ion and Ethyl Chloride in DMSO and THF Probed with Six Different Kinetic Isotope Effects2006Ingår i: J. Org. Chem, nr 71, s. 4742-4747Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The secondary a- and B-deuterium, the a-carbon, the nucleophile carbon, the nucleophile nitrogen, and the chlorine leaving group kinetic isotope effects forthe SN2 reaction between cyanide ion an dethyl chloride were determined in the very slightly polar solvent THF at 30 C. A comparison of these KIEs with those reported earlier for the same reaction in the polar solvent DMSO shows that the transition state in THF is only sligthly tighter with very slightly shorter NC-Ca-CI bonds. This minor change in transition state structure does not account for the different transition structures that were earlier suggested by interpreting the experimental KIEs and the gas-phase calculations, respectively. It therefore seems unlikely that the different transition states suggested by the two methods are due to the lack of appropriate solvent modeling in the theoretical calculations. Previously it was predicted that the transition state of SN2 reactions where the nucleophile and the leaving group have the same charge would be unaffected by a charge in solvent. The experimental KIEs support this view.

  • 22. Froklage, Femke E
    et al.
    Syvänen, Stina
    Leiden University.
    Hendrikse, N Harry
    Huisman, Marc C
    Molthoff, Carla Fm
    Tagawa, Yoshihiko
    Reijneveld, Jaap C
    Heimans, Jan J
    Lammertsma, Adriaan A
    Eriksson, Jonas
    VU University Medical Center Amsterdam.
    de Lange, Elizabeth Cm
    Voskuyl, Rob A
    [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein.2012Ingår i: EJNMMI research, ISSN 2191-219X, Vol. 2, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: [11C]Flumazenil and positron emission tomography (PET) are used clinically to assess gamma-aminobutyric acid (GABA)-ergic function and to localize epileptic foci prior to resective surgery. Enhanced P-glycoprotein (P-gp) activity has been reported in epilepsy and this may confound interpretation of clinical scans if [11C]flumazenil is a P-gp substrate. The purpose of this study was to investigate whether [11C]flumazenil is a P-gp substrate.

    METHODS: [11C]Flumazenil PET scans were performed in wild type (WT) (n = 9) and Mdr1a/1b, (the genes that encode for P-gp) double knockout (dKO) (n = 10) mice, and in naive rats (n = 10). In parallel to PET scanning, [11C]flumazenil plasma concentrations were measured in rats. For 6 of the WT and 6 of the dKO mice a second, [11C]flumazenil scan was acquired after administration of the P-gp inhibitor tariquidar. Cerebral [11C]flumazenil concentrations in WT and Mdr1a/1b dKO mice were compared (genetic disruption model). Furthermore, pre and post P-gp-blocking cerebral [11C]flumazenil concentrations were compared in all animals (pharmacological inhibition model).

    RESULTS: Mdr1a/1b dKO mice had approximately 70% higher [11C]flumazenil uptake in the brain than WT mice. After administration of tariquidar, cerebral [11C]flumazenil uptake in WT mice increased by about 80% in WT mice, while it remained the same in Mdr1a/1b dKO mice. In rats, cerebral [11C]flumazenil uptake increased by about 60% after tariquidar administration. Tariquidar had only a small effect on plasma clearance of flumazenil.

    CONCLUSIONS: The present study showed that [11C]flumazenil is a P-gp substrate in rodents. Consequently, altered cerebral [11C]flumazenil uptake, as observed in epilepsy, may not reflect solely GABAA receptor density changes but also changes in P-gp activity.

  • 23. Golla, Sandeep S V
    et al.
    Boellaard, Ronald
    Oikonen, Vesa
    Hoffmann, Anja
    van Berckel, Bart N M
    Windhorst, Albert D
    Virta, Jere
    Haaparanta-Solin, Merja
    Luoto, Pauliina
    Savisto, Nina
    Solin, Olof
    Valencia, Ray
    Thiele, Andrea
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Schuit, Robert C
    Lammertsma, Adriaan A
    Rinne, Juha O
    Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients2015Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 5, s. 766-772Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([(18)F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [(18)F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250 ± 10 MBq [(18)F]DPA-714. The model that provided the best fits to tissue time activity curves (TACs) was selected based on Akaike Information Criterion and F-test. The reversible two tissue compartment plasma input model with blood volume parameter was the preferred model for quantification of [(18)F]DPA-714 kinetics, irrespective of scan duration, volume of interest, and underlying volume of distribution (VT). Simplified reference tissue model (SRTM)-derived binding potential (BPND) using cerebellar gray matter as reference tissue correlated well with plasma input-based distribution volume ratio (DVR). These data suggest that [(18)F]DPA-714 cannot be used for separating individual AD patients from healthy subjects, but further studies including TSPO binding status are needed to substantiate these findings.

  • 24. Golla, Sandeep S V
    et al.
    Boellaard, Ronald
    Oikonen, Vesa
    Hoffmann, Anja
    van Berckel, Bart N M
    Windhorst, Albert D
    Virta, Jere
    Te Beek, Erik T
    Groeneveld, Geert Jan
    Haaparanta-Solin, Merja
    Luoto, Pauliina
    Savisto, Nina
    Solin, Olof
    Valencia, Ray
    Thiele, Andrea
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Schuit, Robert C
    Lammertsma, Adriaan A
    Rinne, Juha O
    Parametric Binding Images of the TSPO Ligand 18F-DPA-714.2016Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, nr 10, s. 1543-1547Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    (18)F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of (18)F-DPA-714 binding.

    METHODS: Ninety-minute dynamic (18)F-DPA-714 PET scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer disease (AD) patients were used. Plasma-input-based Logan graphical analysis and spectral analysis were used to generate parametric volume of distribution (VT) images. Five versions of Ichise, reference Logan, and 2 basis function implementations (receptor parametric mapping and simplified reference tissue model 2 [SRTM2]) of SRTM, all using gray matter cerebellum as the reference region, were applied to generate nondisplaceable binding potential (BPND) images.

    RESULTS: Plasma-input Logan analysis (r(2) = 0.99; slope, 0.88) and spectral analysis (r(2) = 0.99, slope, 0.93) generated estimates of VT that correlated well with values obtained using nonlinear regression. BPND values generated using SRTM2 (r(2) = 0.83; slope, 0.95) and reference Logan analysis (r(2) = 0.88; slope, 1.01) correlated well with nonlinear regression-based estimates.

    CONCLUSION: Both Logan analysis and spectral analysis can be used to obtain quantitatively accurate VT images of (18)F-DPA-714. In addition, SRTM2 and reference Logan analysis can provide accurate BPND images. These parametric images could be used for voxel-based comparisons.

  • 25.
    Gustafsson, Sofia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Syvänen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Hammarlund-Udenaes, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Combined PET and microdialysis for in vivo estimation of drug blood-brain barrier transport and brain unbound concentrations2017Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 155, s. 177-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Methods to investigate blood-brain barrier transport and pharmacologically active drug concentrations in the human brain are limited and data translation between species is challenging. Hence, there is a need to further develop the read-out of techniques like positron emission tomography ( PET) for studying neuropharmacokinetics. PET has a high translational applicability from rodents to man and measures total drug concentrations in vivo. The aim of the present study was to investigate the possibility of translating total drug concentrations, acquired through PET, to unbound concentrations, resembling those measured in the interstitial fluid by microdialysis sampling. Simultaneous PET scanning and brain microdialysis sampling were performed in rats throughout a 60 min infusion of [N-methyl-C-11] oxycodone in combination with a therapeutic dose of oxycodone and during a 60 min follow up period after the end of infusion. The oxycodone concentrations acquired with PET were converted into unbound concentrations by compensating for brain tissue binding and brain intracellular distribution, using the unbound volume of distribution in brain (Vu, brain), and were compared to microdialysis measurements of unbound concentrations. A good congruence between the methods was observed throughout the infusion. However, an accumulating divergence in the acquired PET and microdialysis data was apparent and became more pronounced during the elimination phase, most likely due to the passage of radioactive metabolites into the brain. In conclusion, the study showed that PET can be used to translate non-invasively measured total drug concentrations into unbound concentrations as long as the contribution of radiolabelled metabolites is minor or can be compensated for.

  • 26. Heurling, Kerstin
    et al.
    Ashton, Nicholas J
    Leuzy, Antoine
    Zimmer, Eduardo R
    Blennow, Kaj
    Zetterberg, Henrik
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Schöll, Michael
    Synaptic vesicle protein 2A as a potential biomarker in synaptopathies2019Ingår i: Molecular and Cellular Probes, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 97, s. 34-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measuring synaptic density in vivo using positron emission tomography (PET) imaging-based biomarkers targeting the synaptic vesicle protein 2A (SV2A) has received much attention recently due to its potential research and clinical applications in synaptopathies, including neurodegenerative and psychiatric diseases. Fluid-based biomarkers in proteinopathies have previously been suggested to provide information on pathology and disease status that is complementary to PET-based measures, and the same can be hypothesized with respect to SV2A. This review provides an overview of the current state of SV2A PET imaging as a biomarker of synaptic density, the potential role of fluid-based biomarkers for SV2A, and related future perspectives.

  • 27.
    Jonasson, My
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Chiotis, Konstantinos
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Leuzy, Antoine
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Nordberg, Agneta
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PETManuskript (preprint) (Övrigt vetenskapligt)
  • 28.
    Jonasson, My
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Chiotis, Konstantinos
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Leuzy, Antoine
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
    Nordberg, Agneta
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden;Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET.2019Ingår i: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 22, artikel-id 101681Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [18F]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [18F]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R1) parametric images. Nine AD patients and nine controls underwent 90 min [18F]THK5317 scans. SUVR-1 was calculated at transient equilibrium (TE) and for seven different 20 min intervals and compared with distribution volume ratio (DVR; reference Logan). Cerebellar grey matter (MRI) was used as reference region. A supervised cluster analysis (SVCA) method was implemented to automatically generate a reference region, directly from the dynamic PET volume without the need of a structural MRI scan, for computation of SUVR-1 and R1 images for a scan duration matching the optimal timing. TE was reached first in putamen, frontal- and parietal cortex at 22 ± 4 min for AD patients and in putamen at 20 ± 0 min in controls. Over all regions and subjects, SUVR20-40-1 correlated best with DVR-1, R2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R2 = 0.93 for SUVR20-40-1; R2 = 0.94 for R1). SUVR20-40 allows for accurate semi-quantitative assessment of tau pathology and SVCA may be used to obtain a reference region for calculation of both SUVR-1 and R1 with 40 min scan duration.

  • 29.
    Jonasson, My
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Univ Uppsala Hosp, Med Phys, Uppsala, Sweden.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Chiotis, Konstantinos
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.
    Saint-Aubert, Laure
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.
    Wilking, Helena
    Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Sprycha, Margareta
    Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Borg, Beatrice
    Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Thibblin, Alf
    Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden.
    Nordberg, Agneta
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.; Karolinska Univ, Huddinge Hosp, Dept Geriatr Med, Stockholm, Sweden.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Univ Uppsala Hosp, Med Phys, Uppsala, Sweden.
    Tracer kinetic analysis of (S)-18F-THK5117 as a PET tracer for assessing tau pathology.2016Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, nr 4, s. 574-581Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Because a correlation between tau pathology and the clinical symptoms of Alzheimer's disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to tau protein. The aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand (S)-(18)F-THK5117.

    METHODS: 9 subjects (5 with AD, 4 with mild cognitive impairment) received a 90 min dynamic (S)-(18)F-THK5117 PET scan. Arterial blood was sampled for measurement of blood radioactivity and metabolite analysis. VOI-based analysis was performed using plasma-input models; single-tissue and two-tissue (2TCM) compartment models and plasma-input Logan, and reference tissue models; simplified reference tissue model (SRTM), reference Logan and standardised uptake value ratio (SUVr). Cerebellum grey matter was used as reference region. Voxel-level analysis was performed using basis function implementations of SRTM, reference Logan and SUVr. Regionally averaged voxel values were compared to VOI-based values from the optimal reference tissue model and simulations were made to assess accuracy and precision. In addition to 90 min, initial 40 and 60 min data were analysed.

    RESULTS: Plasma-input Logan distribution volume ratio (DVR)-1 values agreed well with 2TCM DVR-1 values (R2=0.99, slope=0.96). SRTM binding potential (BPND) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 (R2=1.00, slope≈1.00) while SUVr70-90-1 values correlated less well and overestimated binding. Agreement between parametric methods and SRTM was best for reference Logan (R2=0.99, slope=1.03). SUVr70-90-1 values were almost 3 times higher than BPND values in white matter and 1.5 times higher in grey matter. Simulations showed poorer accuracy and precision for SUVr70-90-1 values than for the other reference methods. SRTM BPND and reference Logan DVR-1 values were not affected by a shorter scan duration of 60 min.

    CONCLUSION: SRTM BPND and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 values. VOI-based data analyses indicated robust results for scan durations of 60 min. Reference Logan generated quantitative (S)-(18)F-THK5117 DVR-1 parametric images with the greatest accuracy and precision, and with a much lower white matter signal than seen with SUVr-1 images.

  • 30.
    Lemoine, Laetitia
    et al.
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Novum, S-14157 Stockholm, Sweden.
    Saint-Aubert, Laure
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Novum, S-14157 Stockholm, Sweden.
    Marutle, Amelia
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Novum, S-14157 Stockholm, Sweden.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Univ Uppsala Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Univ Uppsala Hosp, PET Ctr, Ctr Med Imaging, Uppsala, Sweden.
    Ghetti, Bernardino
    Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA.
    Okamura, Nobuyuki
    Tohoku Univ, Sch Med, Dept Pharmacol, Sendai, Miyagi 980, Japan.
    Nennesmo, Inger
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.
    Gillberg, Per-Göran
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Novum, S-14157 Stockholm, Sweden.
    Nordberg, Agneta
    Karolinska Inst, Div Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res,Novum, S-14157 Stockholm, Sweden; Karolinska Univ, Dept Geriatr Med, Huddinge Hosp, Stockholm, Sweden.
    Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue2015Ingår i: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 3, artikel-id 40Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:  The accumulation of neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, starts spreading early in specific regions in the course of Alzheimer's disease (AD), correlating with the progression of memory dysfunction. The non-invasive imaging of tau could therefore facilitate the early diagnosis of AD, differentiate it from other dementing disorders and allow evaluation of tau immunization therapy outcomes. In this study we characterized the in vitro binding properties of THK5117, a tentative radiotracer for positron emission tomography (PET) imaging of tau brain deposits.

    RESULTS: Saturation and competition binding studies of (3)H-THK5117 in post-mortem AD brain tissue showed the presence of multiple binding sites. THK5117 binding was significantly higher in hippocampal (p < 0.001) and temporal (p < 0.01) tissue homogenates in AD compared to controls. Autoradiography studies with (3)H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo (18)F-FDG PET investigations. The three AD cases showed distinct differences in regional THK5117 binding that were also observed in tau immunohistopathology as well as in clinical presentation. A negative correlation between in vivo (18)F-FDG PET and in vitro (3)H-THK5117 autoradiography was observed in two of the three AD cases.

    CONCLUSIONS: This study supports that new tau PET tracers will provide further understanding on the role of tau pathology in the diversity of the clinical presentation in AD.

  • 31.
    Lubberink, Mark
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Med Phys..
    Appel, Lieuwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Med Imaging Ctr..
    Lindskog, K.
    Uppsala Univ Hosp, Med Phys..
    Danfors, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Med Imaging Ctr..
    Sprycha, M.
    Uppsala Univ Hosp, Med Imaging Ctr..
    Daging, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Uppsala Univ Hosp, Neurol..
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi. Uppsala Univ Hosp, Med Imaging Ctr..
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala Univ Hosp, Med Imaging Ctr..
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala Univ Hosp, Neurol..
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning. Uppsala Univ Hosp, Med Imaging Ctr..
    Quantitative assessment of synaptic density using the SV2A ligand C-11-UCBA in humans2017Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 74-74Artikel i tidskrift (Övrigt vetenskapligt)
  • 32.
    Lubberink, Mark
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Jonasson, My
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Chiotis, K.
    Karolinska Inst, Translat Alzheimer Neurobiol, Stockholm, Sweden..
    Saint-Aubert, L.
    Karolinska Inst, Translat Alzheimer Neurobiol, Stockholm, Sweden..
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Okamura, N.
    Tohoku Univ, Sch Med, Pharmacol, Sendai, Miyagi, Japan..
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Nordberg, A.
    Karolinska Inst, Translat Alzheimer Neurobiol, Stockholm, Sweden..
    Tracer kinetic analysis of [18f](s)-thk5117 as a pet tracer for tau pathology2016Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, nr Suppl. 1, s. 16-17, artikel-id 63Artikel i tidskrift (Övrigt vetenskapligt)
  • 33.
    Lubberink, Mark
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Jonasson, My
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Chiotis, Konstantinos
    Saint-Aubert, Laure
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Okamura, Nobuyuki
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Nordberg, Agneta
    Tracer kinetic analysis of (S)-[F-18]THK5117 as a PET tracer for tau pathology2015Konferensbidrag (Övrigt vetenskapligt)
  • 34. Mansor, Syahir
    et al.
    Yaqub, Maqsood
    Boellaard, Ronald
    Froklage, Femke E
    de Vries, Anke
    Bakker, Esther D M
    Voskuyl, Rob A
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Schwarte, Lothar A
    Verbeek, Joost
    Windhorst, Albert D
    Lammertsma, Adriaan A
    Parametric Methods for Dynamic (11)C-Phenytoin PET Studies.2017Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, nr 3, s. 479-483Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, the performance of various methods for generating quantitative parametric images of dynamic (11)C-phenytoin PET studies was evaluated. Methods: Double-baseline 60-min dynamic (11)C-phenytoin PET studies, including online arterial sampling, were acquired for 6 healthy subjects. Parametric images were generated using Logan plot analysis, a basis function method, and spectral analysis. Parametric distribution volume (VT) and influx rate (K1) were compared with those obtained from nonlinear regression analysis of time-activity curves. In addition, global and regional test-retest (TRT) variability was determined for parametric K1 and VT values. Results: Biases in VT observed with all parametric methods were less than 5%. For K1, spectral analysis showed a negative bias of 16%. The mean TRT variabilities of VT and K1 were less than 10% for all methods. Shortening the scan duration to 45 min provided similar VT and K1 with comparable TRT performance compared with 60-min data. Conclusion: Among the various parametric methods tested, the basis function method provided parametric VT and K1 values with the least bias compared with nonlinear regression data and showed TRT variabilities lower than 5%, also for smaller volume-of-interest sizes (i.e., higher noise levels) and shorter scan duration.

  • 35.
    Nordeman, Patrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Yngve, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wilking, Helena
    Gustavsson, Sven Åke
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Automated GMP-production of α-[11 C]methyl-L-tryptophan using a tracer production system (TPS)2018Ingår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 61, nr 14, s. 1106-1109Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The radiosynthesis and GMP validation of [11 C]AMT for human use are described. Three consecutive batches were produced giving 940-3790 MBq (4%-17% RCY, decay corrected, based on [11 C]CO2 ) of the tracer. The molar activity at the end of synthesis was 19 to 35 GBq/μmol, the radiochemical purity was ≥98%, and the enantiomeric purity was >99%. While the synthesis method was automated using a new generation of synthesis equipment, tracer production system developed in house, the method should be readily applicable to other synthesis platforms with minor modifications.

  • 36.
    Odell, Luke R.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Åkerbladh, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Schembri, Luke S
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Nordeman, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Roslin, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Carbonylations beyond aryl-X: Development of new multicomponent reactions2018Ingår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Artikel i tidskrift (Övrigt vetenskapligt)
  • 37. Oprea-Lager, Daniela E
    et al.
    Vincent, Andrew D
    van Moorselaar, Reindert J A
    Gerritsen, Winald R
    van den Eertwegh, Alfons J M
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Boellaard, Ronald
    Hoekstra, Otto S
    Dual-Phase PET-CT to Differentiate [(18)F]Fluoromethylcholine Uptake in Reactive and Malignant Lymph Nodes in Patients with Prostate Cancer2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 10, s. e48430-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To investigate whether time-trends of enhanced [(18)F]Fluoromethylcholine ([(18)F]FCH) in lymph nodes (LN) of prostate cancer (PCa) patients can help to discriminate reactive from malignant ones, and whether single time point standardized uptake value (SUV) measurements also suffice.

    PROCEDURES: 25 PCa patients with inguinal (presumed benign) and enlarged pelvic LN (presumed malignant) showing enhanced [(18)F]FCH uptake at dual-phase PET-CT were analyzed. Associations between LN status (benign versus malignant) and SUV(max) and SUV(meanA50), determined at 2 min (early) and 30 min (late) post injection, were assessed. We considered two time-trends of [(18)F]FCH uptake: type A (SUV early > SUV late) and type B (SUV late ≥ SUV early). Histopathology and/or follow-up were used to confirm the assumption that LN with type A pattern are benign, and LN with type B pattern malignant.

    RESULTS: Analysis of 54 nodes showed that LN status, time-trends, and 'late' (30 min p.i.) SUV(max) and SUV(meanA50) parameters were strongly associated (P<0.0001). SUV(max) relative difference was the best LN status predictor. All but one inguinal LN showed a decreasing [(18)F]FCH uptake over time (pattern A), while 95% of the pelvic nodes presented a stable or increasing uptake (pattern B) type.

    CONCLUSIONS: Time-trends of enhanced [(18)F]FCH uptake can help to characterize lymph nodes in prostate cancer patients. Single time-point SUV measurements, 30 min p.i., may be a reasonable alternative for predicting benign versus malignant status of lymph nodes, but this remains to be validated in non-enlarged pelvic lymph nodes.

  • 38. Peeters, Sarah G J A
    et al.
    Zegers, Catharina M L
    Lieuwes, Natasja G
    van Elmpt, Wouter
    Eriksson, Jonas
    VU Medical Center Amsterdam .
    van Dongen, Guus A M S
    Dubois, Ludwig
    Lambin, Philippe
    A Comparative Study of the Hypoxia PET Tracers [(18)F]HX4, [(18)F]FAZA, and [(18)F]FMISO in a Preclinical Tumor Model.2015Ingår i: International journal of radiation oncology, biology, physics, ISSN 1879-355X, Vol. 91, nr 2, s. 351-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [(18)F]FMISO, [(18)F]FAZA, and [(18)F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification.

    METHODS AND MATERIALS: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing.

    RESULTS: TBR was stabilized and maximal at 2 hours p.i. for [(18)F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [(18)F]HX4 (7.2 ± 0.7), whereas [(18)F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [(18)F]FMISO (R = 0.86; Dice coefficient = 0.76) and [(18)F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [(18)F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [(18)F]HX4 and [(18)F]FAZA upon 7% oxygen breathing. Only [(18)F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen.

    CONCLUSIONS: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put forward.

  • 39. Peeters, SarahG.J.A.
    et al.
    Dubois, Ludwig
    Lieuwes, NatasjaG.
    Laan, Dennis
    Mooijer, Martien
    Schuit, RobertC.
    Vullo, Daniela
    Supuran, ClaudiuT.
    Eriksson, Jonas
    VU University Medical Center Amsterdam.
    Windhorst, AlbertD.
    Lambin, Philippe
    [18F]VM4-037 MicroPET Imaging and Biodistribution of Two In Vivo CAIX-Expressing Tumor Models2015Ingår i: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, s. 1-5Artikel i tidskrift (Refereegranskat)
  • 40.
    Poot, Alex J
    et al.
    VU University Medical Center, Amsterdam, the Netherlands.
    van der Wildt, Berend
    VU University Medical Center, Amsterdam, the Netherlands.
    Stigter-van Walsum, Marijke
    VU University Medical Center, Amsterdam, the Netherlands.
    Rongen, Marissa
    VU University Medical Center, Amsterdam, the Netherlands.
    Schuit, Robert C
    VU University Medical Center, Amsterdam, the Netherlands.
    Hendrikse, N Harry
    VU University Medical Center, Amsterdam, the Netherlands.
    Eriksson, Jonas
    VU University Medical Center, Amsterdam, the Netherlands.
    van Dongen, Guus A M S
    VU University Medical Center, Amsterdam, the Netherlands.
    Windhorst, Albert D
    VU University Medical Center, Amsterdam, the Netherlands.
    [(11)C]Sorafenib: Radiosynthesis and preclinical evaluation in tumor-bearing mice of a new TKI-PET tracer.:  2013Ingår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 40, nr 4, s. 488-497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Tyrosine kinase inhibitors (TKIs) like sorafenib are important anticancer therapeutics with thus far limited treatment response rates in cancer patients. Positron emission tomography (PET) could provide the means for selection of patients who might benefit from TKI treatment, if suitable PET tracers would be available. The aim of this study was to radiolabel sorafenib (1) with carbon-11 and to evaluate its potential as TKI-PET tracer in vivo. METHODS: Synthetic methods were developed in which sorafenib was labeled at two different positions, followed by a metabolite analysis in rats and a PET imaging study in tumor-bearing mice. RESULTS: [methyl-(11)C]-1 and [urea-(11)C]-1 were synthesized in yields of 59% and 53%, respectively, with a purity of >99%. The identity of the products was confirmed by coinjection on HPLC with reference sorafenib. In an in vivo metabolite analysis [(11)C]sorafenib proved to be stable. The percentage of intact product in blood-plasma after 45min was 90% for [methyl-(11)C]-1 and 96% for [urea-(11)C]-1, respectively. Due to the more reliable synthesis, further research regarding PET imaging was performed with [methyl-(11)C]-1 in nude mice bearing FaDu (head and neck cancer), MDA-MB-231 (breast cancer) or RXF393 (renal cancer) xenografts. Highest tracer accumulation at a level of 2.52±0.33%ID/g was observed in RXF393, a xenograft line extensively expressing the sorafenib target antigen Raf-1 as assessed by immunohistochemistry. CONCLUSION: In conclusion, we have synthesized [(11)C]sorafenib as PET tracer, which is stable in vivo and has the capability to be used as PET tracer for imaging in tumor-bearing mice.

  • 41. Postnov, Andrey
    et al.
    Froklage, Femke E
    van Lingen, Arthur
    Reijneveld, Jaap C
    Hendrikse, N Harry
    Windhorst, Albert D
    Schuit, Robert C
    Eriksson, Jonas
    VU university medical center Amsterdam.
    Lammertsma, Adriaan A
    Huisman, Marc C
    Radiation Dose of the P-Glycoprotein Tracer 11C-Laniquidar.2013Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, nr 12, s. 2101-2103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resistance to current drug therapy is an important issue in the treatment of epilepsy. Inadequate access of central nervous system drugs to their targets in the brain may be caused by overexpression or overactivity of multidrug transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier. Laniquidar, an inhibitor of P-gp, has been labeled with (11)C for use in PET studies of P-gp expression in humans. Given potential interspecies differences in biodistribution, the purpose of this study was to ensure safe use of (11)C-laniquidar by determining the dosimetry of (11)C-laniquidar using whole-body PET studies.

    METHODS: Six healthy volunteers were subjected to a series of 10 whole-body PET scans within approximately 70 min. Five blood samples were taken during the series.

    RESULTS: High uptake of (11)C-laniquidar was seen in liver, spleen, kidneys, and lung, whereas brain uptake was low. The effective dose for (11)C-laniquidar was 4.76 ± 0.13 and 3.69 ± 0.01 μSv·MBq(-1) for women and men, respectively.

    CONCLUSION: Biodistribution and measured effective dose indicate that (11)C-laniquidar is a safe tracer for PET imaging, with a total dose of about 2 mSv for a brain PET/CT protocol.

  • 42. Potschka, H.
    et al.
    Bogdanovic, R. M.
    Syvänen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Michler, C.
    Russmann, V
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Windhorst, A. D.
    Lammertsma, A. A.
    de Lange, E. C.
    Voskuyl, R. A.
    Molecular Imaging of Inflammation Reveals Differences Between Drug-Resistant and Drug-Sensitive Animals in a Chronic Model of Temporal Lobe Epilepsy2014Ingår i: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 55, nr Suppl. 2, s. 32-32Artikel i tidskrift (Övrigt vetenskapligt)
  • 43.
    Rokka, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Fang, Xiaotian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hultqvist, Greta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Faresjö, Rebecca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Olberg, Dag
    Oslo University.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sehlin, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Syvanen, Stina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Journal of Labelled Compounds and Pharmaceuticals: Neurosciences session2019Ingår i: ISRS 2019, Wiley Online Library , 2019, Vol. 62, s. S78-S79Konferensbidrag (Refereegranskat)
  • 44.
    Roslin, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    De Rosa, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Deuther-Conrad, Winnie
    Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, 04318 Leipzig, Germany.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Brust, Peter
    Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, 04318 Leipzig, Germany.
    Larhed, Mats
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Synthesis and In Vitro Evaluation of 5-Substituted Benzovesamicol Analogs containing N-Substituted Amides as Potential Positron Emission Tomography Tracers for the Vesicular Acetylcholine Transporter2017Ingår i: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 25, nr 19, s. 5095-5106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Herein, new ligands for the vesicular acetylcholine transporter (VAChT), based on a benzovesamicol scaffold, are presented. VAChT is acknowledged as a marker for cholinergic neurons and a positron emission tomography tracer for VAChT could serve as a tool for quantitative analysis of cholinergic neuronal density. With an easily accessible triflate precursor, aminocarbonylations were utilized to evaluate the chemical space around the C5 position on the tetrahydronaphthol ring. Synthesized ligands were evaluated for their affinity and selectivity for VAChT. Small, preferably aromatic, N-substituents proved to be more potent than larger substituents. Of the fifteen compounds synthesized, benzyl derivatives (+/-)-7i and (+/-)-7l had the highest affinities for VAChT. Compound (+/-)-7i was chosen to investigate the importance of stereochemistry for binding to VAChT and selectivity toward the sigma(1) and sigma(2) receptors. Enantiomeric resolution gave (+/-)-7i and (-)-7i, and the eutomer showed seven times better affinity. Although racemate (+/-)-7i was initially promising, the affinity of (-)-7i for VAChT was not better than 56.7 nM which precludes further preclinical evaluation. However, the nanomolar binding together with the ready synthesis of [C-11]-(+/-)-7i shows that (-)-7i can serve as a scaffold for future optimizations to provide improved C-11-labelled VAChT PET tracers.

  • 45.
    Schembri, Luke S
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Palladium(0)-Catalyzed Carbonylative Synthesis of N-Acylsulfonamides via Regioselective Acylation2019Ingår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 84, nr 11, s. 6970-6981Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    N-Acylsulfonamides represent an important bioisostere of carboxylic acids that allow for greater molecular elaboration and enhanced hydrogen bonding capabilities. Herein, we present a mild and convenient palladium(0)-catalyzed synthesis of N-acylsulfonamides via the carbonylative coupling of sulfonyl azides and electron-rich heterocycles. The reaction proceeds via in situ generation of a sulfonyl isocyanate followed by regioselective acylation of an indole or pyrrole nucleophile. This approach has been used to synthesize 34 indole- and pyrrole-substituted N-acylsulfonamides in yields of up to 95%. Importantly, this process is ligand-free and compatible with an ex situ solid CO source and requires only slightly elevated temperatures, making it a highly attractive method for the preparation of this important class of compounds. This study further investigated the possibility of labeling N-acylsulfonamides with carbon-11 to facilitate biological evaluation and in vivo studies with positron emission tomography.

  • 46.
    Stevens, Marc
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Chow, Chow
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Asplund, Veronika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Bogdan, Mitran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Åberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Odell, Luke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Synthesis of 11C-labelled Sulfonyl Carbamates via a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols and [11C]CO2016Ingår i: ChemistryOpen, ISSN 2191-1363, Vol. 58, nr 3, s. 566-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Herein we describe the development of new methodologyfocusing on 11C-labelling of sulfonyl carbamates in a multicomponentreaction comprising a sulfonyl azide, an alkyl alcohol and [11C]CO. Anumber of 11C-labelled sulfonyl carbamates were synthesised andisolated, and the developed methodology was then applied in thepreparation of a biologically active molecule. The target compoundwas obtained in 18±8% isolated radiochemical yield and wasevaluated for binding properties in a tumor cell assay, as well asundergoing in vivo biodistribution and imaging studies. Thisrepresents the first successful radiolabelling of C21, a non-peptideangiotensin II receptor subtype 2 agonist currently in clinical trials.

  • 47.
    Stevens, Marc Y.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Chow, Shiao Y.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Asplund, Veronika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Mitran, Bogdan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Åberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Synthesis of C-11-labeled Sulfonyl Carbamates through a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols, and [C-11]CO2016Ingår i: ChemistryOpen, ISSN 2191-1363, Vol. 5, nr 6, s. 566-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe the development of a new methodology focusing on C-11-labeling of sulfonyl carbamates in a multicomponent reaction comprised of a sulfonyl azide, an alkyl alcohol, and [C-11] CO. A number of C-11-labeled sulfonyl carbamates were synthesized and isolated, and the developed methodology was then applied in the preparation of a biologically active molecule. The target compound was obtained in 24 +/- 10% isolated radiochemical yield and was evaluated for binding properties in a tumor cell assay; in vivo biodistribution and imaging studies were also performed. This represents the first successful radiolabeling of a non-peptide angiotensin II receptor subtype 2 agonist, C21, currently in clinical trials for the treatment of idiopathic pulmonary fibrosis.

  • 48.
    Syvänen, Stina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Advances in PET Imaging of P-Glycoprotein Function at the Blood-Brain Barrier.2013Ingår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 4, nr 2, s. 225-237Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) restricts substrate compounds from entering the brain and may thus contribute to pharmacoresistance observed in patient groups with refractory epilepsy and HIV. Altered P-gp function has also been implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Positron emission tomography (PET), a molecular imaging modality, has become a promising method to study the role of P-gp at the BBB. The first PET study of P-gp function was conducted in 1998, and during the past 15 years two main categories of P-gp PET tracers have been investigated: tracers that are substrates of P-gp efflux and tracers that are inhibitors of P-gp function. PET, as a noninvasive imaging technique, allows translational research. Examples of this are preclinical investigations of P-gp function before and after administering P-gp modulating drugs, investigations in various animal and disease models, and clinical investigations regarding disease and aging. The objective of the present review is to give an overview of available PET radiotracers for studies of P-gp and to discuss how such studies can be designed. Further, the review summarizes results from PET studies of P-gp function in different central nervous system disorders.

  • 49. Syvänen, Stina
    et al.
    Eriksson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Genchel, Tove
    Lindhe, Örjan
    Antoni, Gunnar
    Långström, Bengt
    [1-11C]Ethyl iodide and [1-11C]propyl iodide in the synthesis of two potential NK1-receptor ligands and initial PET-imagingManuskript (Övrigt vetenskapligt)
  • 50.
    Syvänen, Stina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Eriksson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Genchel, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmaceutisk biokemi.
    Lindhe, Örjan
    Antoni, Gunnar
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging2007Ingår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 7, s. 6-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171.

    METHODS:

    [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S)-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)-2-phenylpiperidin-3-amine (I) and (2S,3S)-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)piperidin-3-amine (II) was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171.

    RESULTS:

    All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II) had no specific binding in striatum. Ligand (I) had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I) displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171.

    CONCLUSION:

    The propyl-analogue (II) cannot be used for detecting changes in NK1-ligand levels, while further studies should be performed with the ethyl-analogue (I).

12 1 - 50 av 62
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf