Domestic 18F Labeled PSMA
Evaluation of the effect of linker on novel targeted PSMA PET probe
Ren Yanan, Liu Teli, Zhu Hua, Yang Xing, Yang Zhi
Published 2023-04-25
Cite as Chin J Nucl Med Mol Imaging, 2023, 43(4): 211-215. DOI: 10.3760/cma.j.cn321828-20230130-00022
Abstract
ObjectiveTo prepare a novel targeted prostate specific membrane antigen (PSMA) molecular probe Al18F-PSMA-136, and evaluate the effects of the change in linker on the biological behavior and tumor targeting ability.
MethodsAl18F-PSMA-136 was prepared by replacing the phenyl of Al18F-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.
ResultsThe Ki values of NOTA-PSMA-136 and NOTA-PSMA-137 were 3.41 and 0.30 nmol/L, respectively. The labeling yield of Al18F-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 Al18F-PSMA-137 was significantly higher than that of Al18F-PSMA-136 (1 h: (1.67±0.24) vs (1.00±0.01) percentage injected activity per 1×105 cells (%IA/1×105 cells): t=4.78, P=0.003; 2 h: (2.11±0.06) vs (1.03±0.06) %IA/1×105 cells; t=19.90, P<0.001). MicroPET/CT imaging showed that Al18F-PSMA-136 and Al18F-PSMA-137 had similar distribution in vivo, mainly concentrated in kidneys, intestine, gallbladder, bladder and tumor. However, the uptake of Al18F-PSMA-137 in tumor was significantly higher than that of Al18F-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).
ConclusionChanges in the NOTA-conjugated linker can significantly affect the PSMA inhibition ability and tumor targeting, and the imaging effect of Al18F-PSMA-137 with strong lipophilicity is superior.
Key words:
Prostatic neoplasms; Prostate-specific membrane antigen; Positron-emission tomography; Amino acids, diamino; Isotope labeling; Fluorine radioisotopes; Tumor cells, cultured
Contributor Information
Ren Yanan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital &
Institute, Beijing 100142, China
Liu Teli
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital &
Institute, Beijing 100142, China
Zhu Hua
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital &
Institute, Beijing 100142, China
Yang Xing
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
Yang Zhi
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital &
Institute, Beijing 100142, China
