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Asplund, Veronika
Publications (9 of 9) Show all publications
Hulsart Billström, G., Selvaraju, R., Estrada, S., Lubberink, M., Asplund, V., Bergman, K., . . . Antoni, G. (2018). Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept. Journal of Controlled Release, 285, 178-186
Open this publication in new window or tab >>Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept
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2018 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 285, p. 178-186Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.

Keywords
Bone morphogenetic protein 2, Bone tissue engineering, Hydrogel, Micro computed tomography, Positron emission tomography, Single-photon emission computed tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356465 (URN)10.1016/j.jconrel.2018.07.012 (DOI)000441737400015 ()30005906 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 262948
Note

G. Hulsart-Billström and R. K. Selvaraju contributed equally to this work and should be regarded as joint first authors.

Available from: 2018-07-28 Created: 2018-07-28 Last updated: 2018-10-10Bibliographically approved
Stevens, M., Chow, C., Estrada, S., Eriksson, J., Asplund, V., Orlova, A., . . . Odell, L. (2016). Synthesis of 11C-labelled Sulfonyl Carbamates via a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols and [11C]CO. ChemistryOpen, 58(3), 566-573
Open this publication in new window or tab >>Synthesis of 11C-labelled Sulfonyl Carbamates via a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols and [11C]CO
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2016 (English)In: ChemistryOpen, ISSN 2191-1363, Vol. 58, no 3, p. 566-573Article in journal (Refereed) Accepted
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.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-296406 (URN)
Available from: 2016-06-16 Created: 2016-06-16 Last updated: 2017-11-28
Stevens, M. Y., Chow, S. Y., Estrada, S., Eriksson, J., Asplund, V., Orlova, A., . . . Odell, L. R. (2016). Synthesis of C-11-labeled Sulfonyl Carbamates through a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols, and [C-11]CO. ChemistryOpen, 5(6), 566-573
Open this publication in new window or tab >>Synthesis of C-11-labeled Sulfonyl Carbamates through a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols, and [C-11]CO
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2016 (English)In: ChemistryOpen, ISSN 2191-1363, Vol. 5, no 6, p. 566-573Article in journal (Refereed) Published
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.

Keywords
AT(2)R agonists, multicomponent reactions, radiochemistry, sulfonyl azides, sulfonyl carbamates
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-316971 (URN)10.1002/open.201600091 (DOI)000393071500012 ()28032026 (PubMedID)
Funder
Carl Tryggers foundation , CTS13:333 CTS14:356Swedish Cancer Society, 2014/474Swedish Research Council, 2015-02509
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-01-13Bibliographically approved
Bulenga, T. N., Selvaraju, R. K., Estrada, S., Asplund, V., Lubberink, M., Velikyan, I. & Eriksson, O. (2014). Dosimetry of 68Ga and 177Lu labeled Exendin4-impact on feasibility of repeated PET imaging and radiotherapy. Paper presented at Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 18-22, 2014, Gothenburg, SWEDEN. European Journal of Nuclear Medicine and Molecular Imaging, 41(S2), S293-S293, Article ID OP607.
Open this publication in new window or tab >>Dosimetry of 68Ga and 177Lu labeled Exendin4-impact on feasibility of repeated PET imaging and radiotherapy
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2014 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, no S2, p. S293-S293, article id OP607Article in journal, Meeting abstract (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-247689 (URN)000348841900433 ()
Conference
Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 18-22, 2014, Gothenburg, SWEDEN
Available from: 2015-04-08 Created: 2015-03-23 Last updated: 2017-12-04Bibliographically approved
Andersson, J., Rosestedt, M., Asplund, V., Yavari, N. & Orlova, A. (2014). In Vitro Therapy Modeling of HER2 Targeting Therapy in Disseminated Prostate Cancer. International Journal of Oncology, 45(5), 2153-2158
Open this publication in new window or tab >>In Vitro Therapy Modeling of HER2 Targeting Therapy in Disseminated Prostate Cancer
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2014 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 45, no 5, p. 2153-2158Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PCa) is the most common cancer type among men. Treatments against advanced PCa are limited and in many cases only palliative. In a later, androgent independent, stage of PCa androgen receptors can be activated without interaction with ligand, i.e., by receptors of tyrosine kinase (RTK) family in the outlaw pathway. Human epidermal growth factor receptors HER2 and EGFR belong to RTK-family. HER2 is one of the main actors in the outlaw pathway with EGFR as the preferable heterodimerizing partner. We hypothesized that information on HER2 expression in advanced PCa could be useful for selection of patients for anti-RTK therapy and monitoring of therapy response. A panel of PCa cell lines (LNCap, PC3, DU-145) was subjected to a 8-week treatment using drugs influencing the RTK: trastuzumab (anti‑HER2), 17-DMAG (Hsp90 inhibitor), alone or in combination, and their HER2 and EGFR expressions were compared with non-treated cells. Treatment with trastuzumab decreased proliferation of LNCap and DU-145 cell lines, while 17-DMAG and trastuzumab/17‑DMAG combination affected all three cell lines. HER2 expression was significantly increased in PC3 cells, the most resistant cell line. On the contrary, in responding cells (LNCap and DU-145) HER2 expression decreased, accompanied by increased EGFR expression. However, additional treatment of cells with cetuximab (anti‑EGFR) did not give any additive effect to trastuzumab. In this study the response to anti-RTK therapy proved to vary between different PCa cell lines. We have demonstrated that RTK targeting treatments may affect the phenotypic profile of PCa tumor cells that correlates with therapy outcome. Observation of such changes during treatment could be used for monitoring and an improved therapy outcome.

Keywords
prostate cancer, HER2, targeted therapy, molecular imaging, in vitro modeling
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-207258 (URN)10.3892/ijo.2014.2628 (DOI)000342713900042 ()25176024 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2013-09-23 Created: 2013-09-11 Last updated: 2017-12-06Bibliographically approved
Selvaraju, R. K., Velikyan, I., Asplund, V., Johansson, L., Wu, Z., Todorov, I., . . . Eriksson, O. (2014). Pre-clinical evaluation of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 for imaging of insulinoma. Nuclear Medicine and Biology, 41(6), 471-476
Open this publication in new window or tab >>Pre-clinical evaluation of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 for imaging of insulinoma
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2014 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 41, no 6, p. 471-476Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Insulinoma is the most common form of pancreatic endocrine tumors responsible for hyperinsulinism in adults. These tumors overexpress glucagon like peptide-1 (GLP-1) receptor, and biologically stable GLP-1 analogs have therefore been proposed as potential imaging agents. Here, we evaluate the potential of a positron emission tomography (PET) tracer, [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4, for imaging and quantification of GLP-1 receptors (GLP-1R) in insulinoma.

METHODS: [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was evaluated for binding to GLP-1R by in vitro autoradiography binding studies in INS-1 tumor from xenografts. In vivo biodistribution was investigated in healthy control mice, INS-1 xenografted and PANC1 xenografted immunodeficient mice at two different doses of peptide: 2.5μg/kg (baseline) and 100μg/kg (block). In vivo imaging of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in xenografted mice was evaluated by small animal PET/CT using a direct comparison with the clinically established insulinoma marker [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP).

RESULTS: GLP-1 receptor density could be quantified in INS-1 tumor biopsies. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 showed significant uptake (p≤0.05) in GLP1-R positive tissues such as INS-1 tumor, lungs and pancreas upon comparison between baseline and blocking studies. In vivo imaging showed concordant results with higher tumor-to-muscle ratio in INS-1 xenografted mice compared with [(11)C]5-HTP.

CONCLUSION: [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 has high affinity and specificity for GLP-1R expressed on insulinoma in vitro and in vivo.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-225057 (URN)10.1016/j.nucmedbio.2014.03.017 (DOI)000336946400005 ()24857864 (PubMedID)
Available from: 2014-05-27 Created: 2014-05-27 Last updated: 2017-12-05Bibliographically approved
Eriksson, O., Selvaraju, R., Borg, B., Asplund, V., Estrada, S. & Antoni, G. (2013). 5-Fluoro-[beta-C-11]-L-tryptophan is a functional analogue of 5-hydroxy-[beta-C-11]-L-tryptophan in vitro but not in vivo. Nuclear Medicine and Biology, 40(4), 567-575
Open this publication in new window or tab >>5-Fluoro-[beta-C-11]-L-tryptophan is a functional analogue of 5-hydroxy-[beta-C-11]-L-tryptophan in vitro but not in vivo
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2013 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 40, no 4, p. 567-575Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: 5-Hydroxy-[β-(11)C]-L-tryptophan ([(11)C]HTP) is an established positron emission tomography (PET) imaging agent for neuroendocrine tumors (NETs). It has also been used for other clinical research purposes in neurology and diabetes. However, its widespread use is limited by the short physical half-life of the radionuclide and a difficult radiosynthesis. Therefore, a Fluorine-18 labeled analogue, 5-[(18)F]Fluoro-L-tryptophan ([(18)F]FTRP), has been proposed as a functional analogue. There is no published method for the synthesis of L-[(18)F]FTRP. We have therefore developed a synthesis of 5-fluoro-[β-(11)C]-L-tryptophan ([(11)C]FTRP), based on the existing chemo-enzymatic method for [(11)C]HTP and evaluated the potential usefulness of radiolabeled FTRP as a substitute for [(11)C]HTP.

METHODS: The in vitro and in vivo behavior of [(11)C]FTRP, including the dependence of key enzymes in the serotonergic metabolic pathway, was investigated in NET cell lines, NET xenograft carrying immunodeficient mice, normal rats and in non-human primate. [(11)C]HTP was used for direct comparison.

RESULTS: Uptake of [(11)C]FTRP in NET cell lines in vitro was mediated by enzymes involved in serotonin synthesis and metabolism, similar to [(11)C]HTP. In vivo biodistribution, either in rodent or non-human primate, was not affected by selectively inhibiting enzymatic steps in the serotonergic metabolic pathway.

CONCLUSION: [(11)C]FTRP has in vitro biological function similar to that of [(11)C]HTP. However, this function is not retained in vivo as shown by biodistribution and PET/CT studies. Radiolabeled FTRP is thus not likely to provide an advantage over [(11)C]HTP in PET imaging in oncology, neurology or diabetes.

Keywords
Neuroendocrine tumors, 5-HTP, FTRP, 5-hydroxytryptophan, Fluoro-tryptophan
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-207795 (URN)10.1016/j.nucmedbio.2013.02.005 (DOI)000325842800019 ()23523525 (PubMedID)
Available from: 2013-09-19 Created: 2013-09-19 Last updated: 2017-12-06Bibliographically approved
Antoni, G., Selvaraju, R., Borg, B., Asplund, V., Estrada, S. & Eriksson, O. (2013). 5-Fluoro-[beta-C-11]-L-tryptophan is a functional analogue of 5-hydroxy-[beta-C-11]-L-tryptophan in vitro but not in vivo. Paper presented at 20th International Symposium on Radiopharmaceutical Sciences; 12-17 May 2013; ICC JEJU, Jeju, Korea. Journal of labelled compounds & radiopharmaceuticals, 56(S1), S367-S367
Open this publication in new window or tab >>5-Fluoro-[beta-C-11]-L-tryptophan is a functional analogue of 5-hydroxy-[beta-C-11]-L-tryptophan in vitro but not in vivo
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2013 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 56, no S1, p. S367-S367Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-203007 (URN)000318694100368 ()
Conference
20th International Symposium on Radiopharmaceutical Sciences; 12-17 May 2013; ICC JEJU, Jeju, Korea
Available from: 2013-07-02 Created: 2013-07-01 Last updated: 2017-12-06Bibliographically approved
Lubberink, M., Tovedal, T., Morell, A., Golla, S., Estrada, S., Asplund, V., . . . Lennmyr, F. (2012). Measurement of absolute cerebral blood flow during cardiopulmonary bypass and selective cerebral perfusion using [O-15]water and PET. Paper presented at 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM), AUG 09-11, 2012, Baltimore, MD. Journal of Cerebral Blood Flow and Metabolism, 32(S1), S157-S158
Open this publication in new window or tab >>Measurement of absolute cerebral blood flow during cardiopulmonary bypass and selective cerebral perfusion using [O-15]water and PET
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2012 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, no S1, p. S157-S158Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-182334 (URN)10.1038/jcbfm.2012.80 (DOI)000307138000164 ()
Conference
9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM), AUG 09-11, 2012, Baltimore, MD
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2017-12-07Bibliographically approved
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