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Imaging of Insulinlike Growth Factor Type 1 Receptor in Prostate Cancer Xenografts Using the Affibody Molecule (111)In-DOTA-Z(IGF1R:4551)
KTH, School of Biotechnology (BIO), Molecular Biotechnology.
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2012 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, no 1, 90-97 p.Article in journal (Refereed) Published
Abstract [en]

One of the pathways leading to androgen independence in prostate cancer involves upregulation of insulinlike growth factor type 1 receptor (IGF-1R). Radionuclide imaging of IGF-1R in tumors might be used for selection of patients who would most likely benefit from IGF-1R-targeted therapy. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of IGF-1R expression in prostate cancer xenografts using a small nonimmunoglobulin-derived binding protein called an Affibody molecule. Methods: The IGF-1R-binding Z(IGF1R:4551) Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. The binding of radiolabeled Z(IGF1R:4551) to IGF-1R-expressing cells was evaluated in vitro and in vivo. Results: DOTA-Z(IGF1R:4551) can be stably labeled with (111)In with preserved specific binding to IGF-1R-expressing cells in vitro. In mice, (111)In-DOTAZ(IGF1R):(4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung, and salivary gland). Receptor saturation experiments demonstrated that targeting of DU-145 prostate cancer xenografts in NMRI nu/nu mice was IGF-1R-specific. The tumor uptake was 1.1 +/- 0.3 percentage injected dose per gram, and the tumor-to-blood ratio was 3.2 +/- 0.2 at 8 h after injection. Conclusion: This study demonstrates the feasibility of in vivo targeting of IGF-1R-expressing prostate cancer xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical tool for stratification of patients with prostate cancer for IGF-1R-targeting therapy.

Place, publisher, year, edition, pages
2012. Vol. 53, no 1, 90-97 p.
Keyword [en]
Affibody molecule, (111)In, molecular imaging, IGF-1R, DU145 xenograft
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-75532DOI: 10.2967/jnumed.111.090829ISI: 000298660900024PubMedID: 22173843Scopus ID: 2-s2.0-84855410318OAI: oai:DiVA.org:kth-75532DiVA: diva2:490841
Note
QC 20120206Available from: 2012-02-06 Created: 2012-02-06 Last updated: 2017-12-08Bibliographically approved

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Gräslund, Torbjörn

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