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Imaging of platelet-derived growth factor receptor β expression in glioblastoma xenografts using affibody molecule 111In-DOTA-Z09591
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Tolmachev)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Tolmachev)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Tolmachev)
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2014 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, no 2, 294-300 p.Article in journal (Refereed) Published
Abstract [en]

The overexpression and excessive signaling of platelet-derived growth factor receptor β (PDGFRβ) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFRβ expression might help to select PDGFRβ targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFRβ expression using an Affibody molecule, a small nonimmunoglobulin affinity protein.

Methods

The PDGFRβ-binding Z09591 Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with 111In. Targeting of the PDGFRβ-expressing U-87 MG glioblastoma cell line using 111In-DOTA-Z09591 was evaluated in vitro and in vivo.

Results

DOTA-Z09591 was stably labeled with 111In with preserved specific binding to PDGFRβ-expressing cells in vitro. The dissociation constant for 111In-DOTA-Z09591 binding to U-87 MG cells was determined to be 92 ± 10 pM. In mice bearing U-87 MG xenografts, the tumor uptake of 111In-DOTA-Z09591 was 7.2 ± 2.4 percentage injected dose per gram and the tumor-to-blood ratio was 28 ± 14 at 2 h after injection. In vivo receptor saturation experiments demonstrated that targeting of U-87 MG xenografts in mice was PDGFRβ-specific. U-87 MG xenografts were clearly visualized using small-animal SPECT/CT at 3 h after injection.

Conclusion

This study demonstrates the feasibility of in vivo visualization of PDGFRβ-expressing xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical imaging tool for PDGFRβ expression during various pathologic conditions.

Place, publisher, year, edition, pages
2014. Vol. 55, no 2, 294-300 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-218568DOI: 10.2967/jnumed.113.121814ISI: 000330926200047PubMedID: 24408895OAI: oai:DiVA.org:uu-218568DiVA: diva2:695991
Available from: 2014-02-12 Created: 2014-02-12 Last updated: 2017-12-06Bibliographically approved

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Tolmachev, VladimirVarasteh, ZohrehHonarvar, HadisHosseinimehr, Seyed JalalEriksson, OlofFrejd, Fredrik YOrlova, Anna

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