Evaluation of the effect of linker on novel targeted PSMA PET probe
10.3760/cma.j.cn321828-20230130-00022
- VernacularTitle:新型靶向PSMA PET探针联接链的效应研究
- Author:
Yanan REN
1
;
Teli LIU
;
Hua ZHU
;
Xing YANG
;
Zhi YANG
Author Information
1. 北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科、国家药监局放射性药物研究与评价重点实验室、恶性肿瘤发病机制及转化研究教育部重点实验室，北京 100142
- Keywords:
Prostatic neoplasms;
Prostate-specific membrane antigen;
Positron-emission tomography;
Amino acids, diamino;
Isotope labeling;
Fluorine radioisotopes;
Tumor
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2023;43(4):211-215
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al 18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability. Methods:Al 18F-PSMA-136 was prepared by replacing the phenyl of Al 18F-PSMA-137 with cyclohexyl in 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA). The inhibition abilities of PSMA of NOTA-PSMA-136 and NOTA-PSMA-137 were determined by N-acetylated-α-linked acidic dipeptidase (NAALADase) method. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio-high-performance liquid chromatography. The PSMA specificity and tumor targeting capability of the probes were investigated in 22Rv1 (PSMA positive-expressing) cells and mouse models. Independent-sample t test was used to analyze the data. Results:The Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al 18F-PSMA-136 was (30.1±8.4)% and the specific activity was (18.7±5.3) GBq/μmol. The radiochemical purities of the two probes were both greater than 95% and the stabilities in vitro were both good. Both probes showed PSMA-specific in 22Rv1 cells, but the uptake of Al 18F-PSMA-137 was significantly higher than that of Al 18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×10 5 cells (%IA/1×10 5 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×10 5 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al 18F-PSMA-136 and Al 18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al 18F-PSMA-137 in tumor was significantly higher than that of Al 18F-PSMA-136 (1 h: 1.78±0.10 vs 0.54±0.08; t=13.29, P<0.001; 2 h: 1.95±0.01 vs 0.52±0.11; t=18.53, P<0.001). Conclusion:Changes in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al 18F-PSMA-137 with strong lipophilicity is superior.
