Development of INER-PP-F11N as the Peptide-Radionuclide Conjugate Drug Against CCK2 Receptor-Overexpressing Tumors.
Journal
International journal of molecular sciences
Journal Volume
26
Journal Issue
14
Start Page
Article number 6565
ISSN
1422-0067
Date Issued
2025-07-08
Author(s)
Chang, Ming-Cheng
Chen, Chun-Tang
Chiang, Ping-Fang
Tang, I-Chung
Peng, Cheng-Liang
Wang, Yuh-Feng
Abstract
This work aimed to evaluate two albumin affinity structure-containing peptide-radionuclide conjugate drugs, INER-PP-F11N-1 and INER-PP-F11N-2, for the diagnosis/treatment of cholecystokinin receptor subtype 2 (CCK2R)-overexpressing cancers. We developed In-111- and Lu-177-labeled INER-PP-F11N radiopharmaceuticals and compared them with the current PP-F11N to investigate metabolic stability, biodistribution, SPECT/CT imaging, and therapeutic responses in CCK2R-expressing tumor xenograft mice. The metabolic stability of [In]In/[Lu]Lu-INER-PP-F11N remained above 90% for up to 144 h after labeling, indicating that the compound is highly stable under in vitro conditions. INER-PP-F11N showed 27% and 11% higher cellular uptake and internalization than PP-F11N, respectively. In vivo SPECT/CT imaging confirmed that INER-PP-F11N could accumulate at the tumor site of mice 24 h after receiving the two radiopharmaceutical agents. Biodistribution analysis revealed a significantly greater tumor uptake and reduced accumulation of INER-PP-F11N in the kidneys compared with PP-F11N. Furthermore, INER-PP-F11N significantly inhibited the growth of the CCK2R-overexpressing tumors in mice. The INER-PP-F11N radiopharmaceutical was superior as a theragnostic agent compared with the current PP-F11N. Our study suggests that INER-PP-F11N may be an innovative radiopharmaceutical agent for CCK2R-overexpressing tumors.
Subjects
CCK2R
INER-PP-F11N
peptide-radionuclide conjugate drug
radiopharmaceutical agent
theragnostic
Type
journal article