uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi. (Bengt Långström)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Centrum för bildanalys. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
Vise andre og tillknytning
2011 (engelsk)Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 54, nr 11, s. 685-692Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR-2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti-angiogenic drugs target VEGF/VEGFR-2 signaling and induce changes in VEGFR-2 prevalence. To monitor VEGFR-2 prevalence in the course of treatment, we are evaluating (68)Ga positron emission tomography imaging agents based on macrocyclic chelators, site-specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR-2 ligand, single-chain (sc) VEGF. The (68)Ga-labeling was performed at room temperature with NOTA (2,2', 2 ''-(1,4,7-triazonane-1,4,7-triyl) triacetic acid) conjugates or at 90 degrees C by using either conventional or microwave heating with NOTA and DOTA (2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid) conjugates. The fastest (similar to 2min) and the highest incorporation (>90%) of (68)Ga into conjugate that resulted in the highest specific radioactivity (similar to 400MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA-and DOTA-containing tracers was validated in 3-D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR-2. The NOTA-containing tracer also displayed a rapid accumulation (similar to 20s after intravenous injection) to steady-state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF-PEG-[(68)Ga] NOTA and scVEGF-PEG-[(68)Ga] DOTA might be promising tracers for monitoring VEGFR-2 prevalence and should be further explored.

sted, utgiver, år, opplag, sider
2011. Vol. 54, nr 11, s. 685-692
Emneord [en]
scVEGF, (68)Ga, radiolabeling, angiogenesis, VEGFR-2, PET
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-108589DOI: 10.1002/jlcr.1909ISI: 000297987200001OAI: oai:DiVA.org:uu-108589DiVA, id: diva2:254747
Tilgjengelig fra: 2009-10-10 Laget: 2009-09-23 Sist oppdatert: 2017-12-13bibliografisk kontrollert
Inngår i avhandling
1. Development of 18F- and 68Ga-Labelled Tracers: Design Perspectives and the Search for Faster Synthesis
Åpne denne publikasjonen i ny fane eller vindu >>Development of 18F- and 68Ga-Labelled Tracers: Design Perspectives and the Search for Faster Synthesis
2009 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

This thesis deals with the design of 18F- and 68Ga-labelled positron emission tomography (PET) tracers and the development of technologies that enable faster and simpler preparation with high specific radioactivity. Techniques like microwave heating and reducing the concentrations of the precursor were investigated with this perspective. A few applications were explored using molecular design perspectives.

A nucleophilic 18F-labelling strategy using perfluoro-containing leaving groups was explored. We observed that [18F]fluoride was interacting with the perfluoro alkyl chains of the substrate, preventing the nucleophilic substitution from taking place. When a perfluoroaryl group was instead used in the leaving group, the substitution took place and purification by fluorous solid-phase extraction was possible.

18F-Labelled analogues of the monoamine oxidase-A inhibitor harmine were prepared by one-step nucleophilic fluorinations and evaluated by in vitro autoradiography, showing high specific binding.

Biotin analogues labelled with 18F and 68Ga were prepared and their binding to avidin evaluated. All analogues retained their binding ability and will be further evaluated in transplantation models with avidin-coated islets of Langerhans.

Peptide design perspectives were used in some examples where the Arg-Gly-Asp (RGD) sequence and a single-chain version of vascular endothelial growth factor (VEGF) protein functionalized with 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) or 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA) as chelators were labelled with 68Ga. The RGD motif and VEGF have high affinity for, respectively, αvβ3 integrin and VEGFR-2 receptor that are overexpressed in angiogenesis process. The 68Ga-labelled scVEGF maintained its functional activity in vitro.

A polypeptide conjugate containing phosphocholine, which has affinity for the C-reactive protein released during the inflammatory process, was labelled with 68Ga for the development of an imaging agent for inflammation in vivo.

Finally [18F]/19F exchange in fluorine-containing compounds was studied in order to investigate whether the exchange reaction can be of practical use for labelling.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2009. s. 48
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 678
Emneord
PET, nucleophilic 18F-fluorination, perfluoro, F-SPE, molecular design, 68Ga, chelators, DOTA, NOTA, microwave, halogen exchange, harmine, biotin, RGD, VEGF, CRP
HSV kategori
Forskningsprogram
Organisk kemi
Identifikatorer
urn:nbn:se:uu:diva-108629 (URN)978-91-554-7626-7 (ISBN)
Disputas
2009-11-26, C8:305, BMC, Husargatan 3, 751 23 Uppsala, Uppsala, 13:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2009-11-05 Laget: 2009-09-24 Sist oppdatert: 2011-03-03bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekst

Personposter BETA

Blom, ElisabethVelikyan, IrinaMonazzam, AzitaRazifar, Pasha

Søk i DiVA

Av forfatter/redaktør
Blom, ElisabethVelikyan, IrinaMonazzam, AzitaRazifar, Pasha
Av organisasjonen
I samme tidsskrift
Journal of labelled compounds & radiopharmaceuticals

Søk utenfor DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric

doi
urn-nbn
Totalt: 986 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf