Development of INER-PP-F11N as the radionuclide theragnostics agent against cholecystokinin B receptor-overexpressed tumors.

Abstract

164 Background: We aimed to evaluate an albumin affinity structure-containing radiopharmaceutical agents INER-PP-F11N-1 and INER-PP-F11N-2 for diagnostic/therapeutic the CCK2R-overexpressed cancers. Methods: We developed the radionuclide labeled In-111/Lu-177-INER-PP-F11N radiopharmaceuticals in comparison with the current PP-F11N to investigate the radiochemical purity, SPECT/CT imaging, bio-distribution, and therapeutic responses in CCK2R-expressing tumor xenograft mice. Results: The radiochemical purity of In-111/Lu-177-INER-PP-F11N radiopharmaceuticals reached more than 90% after 144 hours of labeling. Both INER-PP-F11N increased cellular uptake and internalization 27% and 11% in compared with PP-F11N, respectively. In-vivo SPECT-CT imaging confirmed INER-PP-F11N could accumulate in the tumor site of mice in 24 hours after receiving those two radiopharmaceutical agents. Bio-distribution analysis revealed a significantly greater tumor uptake and reduced accumulation of INER-PP-F11N in kidney in compared with PP-F11N. Furthermore, INER-PP-F11N could significantly inhibit growth of the CCK2R-overexpressing tumors in mice. Conclusions: The INER-PP-F11N radiopharmaceuticals was superior to the current PP-F11N as a theragnostic agent. Our study suggested INER-PP-F11N could be an innovative radiopharmaceutical agent for CCK2R-overexpressing cancer patients.