Abstract
241990
Introduction: Objective: Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have been shown to be ideal tools for the diagnosis and treatment of prostate cancer(PCa). The excellent molecular imaging performance has already been significantly demonstrated with the short-lived isotopes 18F and 68Ga, but its potential is expected to be further exploited using long-lived isotopes. With a half-life of 12.7 hours and lower energy, 64Cu obtained non-inferior image quality compared to 18F. Therefore, we developed a 64Cu-labeled targeted PSMA radiotracer and preliminarily evaluated its potential for PCa imaging through preclinical and pilot clinical studies.
Methods: Methods: 64Cu-PSMA-3Q was synthesized using 64Cu-labeled glutamic acid urea PSMA-3Q, a small molecule of the PSMA. The labeling efficiency and stability were verified by Radio-HPLC. Pharmacokinetics evaluation, biodistribution study, Micro-PET imaging of 64Cu-PSMA-3Q in normal mice and 22RV1 tumor-bearing mice (PSMA +) were performed. In addition, PET/ CT imaging was performed on 10 patients with suspected PCa at 2 h post-injection (p.i.).
Results: Results and Discussion: 64Cu-PSMA-3Q was prepared with high radiochemical yield and stability. The distribution and elimination half-lives of 64Cu-PSMA-3Q were 1.20 min and 82.72 min, respectively. Micro-PET imaging of 64Cu-PSMA-3Q can clearly diferentiate 22Rv1 tumor from background with a high SUVmax（2.23±0.49, 2.59±0.18 and 2.84±0.46 at 1h, 6h and 24h, respectively）and a tumor-to-muscle ratio（15.43±4.44, 20.09±0.95 and 18.06±1.59 at 1h, 6h and 24h, respectively）. In PSMA blockade studies using (S)-2-{3-[(S)-1-carboxy-3-methylbutyl]ureido （ZJ-43）, 64Cu-PSMA-3Q uptake was significantly reduced in the 22RV1 tumor region (P<0.001). A total of fifty-five tumor lesions were detected in 10 Pca patients, and the mean SUVmax values of primary tumors, lymph node metastasis, bone metastases, and tumor-muscle ratios were 20.43±12.99, 7.82±3.76, 20.49±16.73, and 46.53±31.34, respectively. 64Cu-PSMA-3Q uptake in the liver of patients was higher than that of 18F-PSMA-3Q（mean SUVmax：7.74±0.76 vs 3.55±0.41，p<0.001）. However, the slightly higher liver uptake of 64Cu-PSMA-3Q does not affect the detection of primary muscle metastases of prostate cancer.
Conclusions: The novel qualifed PSMA-targeted radiotracer 64Cu-PSMA-3Q was conveniently prepared with favorable SA. The results of preclinical and preliminary human studies exhibited a high specifc uptake in PCa lesions , which indicated the great potential of 64Cu-PSMA-3Q for PCa imaging.
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