RT Journal Article
SR Electronic
T1 Imaging of Insulinlike Growth Factor Type 1 Receptor in Prostate Cancer Xenografts Using the Affibody Molecule <sup>111</sup>In-DOTA-Z<sub>IGF1R:4551</sub>
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 90
OP 97
DO 10.2967/jnumed.111.090829
VO 53
IS 1
A1 Vladimir Tolmachev
A1 Jennie Malmberg
A1 Camilla Hofström
A1 Lars Abrahmsén
A1 Thomas Bergman
A1 Anna Sjöberg
A1 Mattias Sandström
A1 Torbjörn Gräslund
A1 Anna Orlova
YR 2012
UL http://jnm.snmjournals.org/content/53/1/90.abstract
AB 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 ZIGF1R:4551 Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with 111In. The binding of radiolabeled ZIGF1R:4551 to IGF-1R–expressing cells was evaluated in vitro and in vivo. Results: DOTA-ZIGF1R:4551 can be stably labeled with 111In with preserved specific binding to IGF-1R–expressing cells in vitro. In mice, 111In-DOTA-ZIGF1R: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.