68Ga-NOTA-ANCP-PSMA的制备与初步评价

前列腺特异性膜抗原（prostate specific membrane antigen, PSMA）作为理想靶点，⁶⁸Ga标记的PSMA小分子抑制剂可用于前列腺癌诊断、分期和疗效评价。为研发一种新型、具有较好理化性能的⁶⁸Ga标记的PSMA小分子化合物，以1-萘基丙氨酸、4-胺甲基环己甲酸和苯丙氨酸组成的链式氨基酸为侧链，设计了新型的PSMA小分子抑制剂⁶⁸Ga-NOTA-ANCP-PSMA，并对其标记方法和体外理化性质进行了研究。采用固相合成法制备前体化合物，经确证结构后，进行⁶⁸Ga标记。分别对温度、pH、前体化合物投入量等标记条件进行了实验，并测定了放射性标记物的稳定性和脂水分配系数。标记条件为pH=3.0～4.5、90.0～95.0 ℃、前体化合物质量浓度不低于20 mg/L，在优化的标记条件下，标记率可达95%以上。纯化后的标记物在磷酸缓冲液体系下和小牛血清蛋白体系下2 h的体外稳定性较好。脂水分配系数为-1.36±0.01(n=3)，与PSMA-617相比，该化合物的亲脂性稍高。标记化合物的体内分布显示：血液清除较快，以肾脏代谢为主，在非靶器官摄取较低。

Preparation and Preliminary Evaluation of68Ga-NOTA-ANCP-PSMA

Prostate specific membrane antigen(PSMA) as a specific target antigen for prostate cancer has become an ideal target. The use of PSMA labeled with⁶⁸Ga has become a hot topic in prostate cancer diagnosis, staging and efficacy evaluation. To develop a new⁶⁸Ga labeled PSMA compound with better physical and chemical properties, a novel PSMA small molecule inhibitor⁶⁸Ga-NOTA-ANCP-PSMA was designed, with 1-naphthylalanine, tranexamic acid and phenylalanine as the side chain. And its labeling method, physical and chemical properties and preliminary evaluation were carried out.⁶⁸Ga was labeled to the PSMA compound directly, and the labeling conditions such as temperature, pH and precursor compound input amount were tested, respectively. The stability and octanol-water partition coefficient were determined, and the in vitro distribution of normal mice was determined. The labeling conditions should be controlled at pH=3.0-4.5, the labeling temperature was selected at 90.0-95.0 ℃, and the precursor compound concentration was not lower than 20 mg/L. In optimal labeling conditions, the labeling yield achieves to over 95%. The purified labeled compound shows good vitro stability, and radiochemical purity is stable in the PBS system and the serum protein system for 2 hours. The octanol-water partition coefficient is -1.36±0.01(n=3), which is a little higher than PSMA-617. The distribution in normal mice show that the compound clears fast in blood, mainly by kidney metabolism, lower uptake shows in non-target organs. The compound shows good properties, which is expected to be used for the diagnosis of prostate for PET, and provide a basis for developing prostate cancer theranostic targeted molecules probe for the future.