Imaging of insulinlike growth factor type 1 receptor in prostate cancer xenografts using the affibody molecule 111In-DOTA-Z IGF1R:4551

Vladimir Tolmachev, Jennie Malmberg, Camilla Hofström, Lars Abrahmsén, Thomas Bergman, Anna Sjöberg, Mattias Sandström, Torbjörn Gräslund, Anna Orlova

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

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 111In. 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 111In with preserved specific binding to IGF-1R-expressing cells in vitro. In mice, 111In-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.

Original languageEnglish
Pages (from-to)90-97
Number of pages8
JournalJournal of Nuclear Medicine
Volume53
Issue number1
DOIs
Publication statusPublished - 1 Jan 2012
Externally publishedYes

Keywords

  • In
  • Affibody molecule
  • DU145 xenograft
  • IGF-1R
  • Molecular imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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