Preclinical evaluation and first in human study of Al18F radiolabeled ODAP-urea-based PSMA targeting ligand for PET imaging of prostate cancer

作者：Yanan Ren, Chen Liu, Teli Liu, Xiaojiang Duan, Qian Zhang, Jiayue Liu, Pei Wang, Qian Guo, Xing Yang, Peng Du, Hua Zhu, Zhi Yang · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.1030187 · 被引用次数：9 · 研究领域：Prostate Cancer Treatment and Research、Radiopharmaceutical Chemistry and Applications、Peptidase Inhibition and Analysis

Purpose This study aimed to introduce a novel [ 18 F]AlF-labeled ODAP-Urea-based Prostate-specific membrane antigen (PSMA) probe, named [ 18 F]AlF-PSMA-137, which was derived from the successful modification of glutamate-like functional group. The preclinically physical and biological characteristics of the probe were analyzed. Polit clinical PET/CT translation was performed to analyze its feasibility in clinical diagnosis of prostate cancer. Methods [ 18 F]AlF-PSMA-137 was maturely labeled with the [ 18 F]AlF 2+ labeling technique. It was analyzed by radio-HPLC for radiochemical purity and stability analysis in vitro and in vivo . The PSMA specificity was investigated in PSMA-positive (LNCaP) and PSMA-negative (PC3) cells, and the binding affinity was evaluated in LNCaP cells. Micro-PET/CT imaging was performed in mice bearing LNCaP or PC3 tumors. Thirteen patients with newly diagnosed prostate cancer were included for [ 18 F]AlF-PSMA-137 PET/CT imaging. Physiologic biodistribution and tumor burden were semi-quantitatively evaluated and the radiation dosimetry of [ 18 F]AlF-PSMA-137 was estimated. Results The radiochemical yield of [ 18 F]AlF-PSMA-137 was 54.2 ± 10.7% (n = 16) with the radiochemical purity over 99% and the specific activity of 26.36 ± 7.33 GBq/μmol. The binding affinity to PSMA was 2.11 ± 0.63 nM. [ 18 F]AlF-PSMA-137 showed high cell/tumor uptake which can be specifically blocked by PSMA inhibitor. According to the biodistribution in patients, [ 18 F]AlF-PSM...