Preparation And Preliminary Biological Evaluation Of ¹⁸⁸Re-MAG₃-PSMA

Prostate cancer（PC）is the second most common cancer among men globally and the sixth most common cancer in men in China,and it shows an increasing incidence every year.Moreover,high-risk prostate cancer is one of the most common malignant tumors threatening the life and health of elderly men,and its mortality is second only to lung cancer.Early diagnosis,accurate staging,and precise treatment of prostate cancer are very important to reduce mortality.Prostate-specific membrane antigen（PSMA）is highly expressed in prostate tumor cells,and its expression level is closely related to the grading and staging of prostate cancer,so it has become an ideal target for the diagnosis and treatment of prostate cancer.The targeted molecular probes have obtained satisfactory results in the diagnosis and treatment of prostate cancer.The half-life of the nuclide rhenium-188(¹⁸⁸Re)is 16.9 h.Itsβenergy of 2.11 Me V is suitable for the treatment of cancer,while itsγenergy of 155 ke V is optimal for imaging.Meanwhile,the nuclide can be easily obtained from a ¹⁸⁸W/¹⁸⁸Re generator.In this study,we designed and synthesized a new compound MAG₃-PSMA.Rhenium-188 was chelated with mercaptoacetyltriglycine（MAG₃）-PSMA to obtain¹⁸⁸Re-MAG₃-PSMA.The labeling efficiency was greater than 99%under the optimal labeling conditions.Subsequently,the in vitro and in vivo stability of ¹⁸⁸Re-MAG₃-PSMA has been investigated.The experimental results showed that ¹⁸⁸Re-MAG₃-PSMA has good stability in vitro and in vivo.Moreover,the results of pharmacokinetics studies showed that the compound has a short distribution half-life and elimination half-life,in line with the pharmacokinetic characteristics of small molecular compounds.Cell experiments showed that the uptake of ¹⁸⁸Re-MAG₃-PSMA in 22Rv1 cells（PSMA+）was significantly higher than that in PC-3 cells（PSMA-）.Biodistribution experiments were carried out in 22Rv1 tumor-bearing mice.¹⁸⁸Re-MAG₃-PSMA could be rapidly cleared from the blood and specifically concentrated in tumors.Meanwhile,4 h post-injection,¹⁸⁸Re-MAG₃-PSMA showed lower uptake in other organs,and the T/NT has a maximum value.BGC-823（a gastric adenocarcinoma cell with a high PSMA-expressed）tumor-bearing mice were used to study the therapeutic effect of¹⁸⁸Re-MAG₃-PSMA.The results showed that the growth of the tumors was inhibited by ¹⁸⁸Re-MAG₃-PSMA.