18F-标记的前列腺特异性膜抗原JK-PSMA-7的制备及初步PET/CT显像

为合成一种新型¹⁸F^-标记的前列腺特异性膜抗原¹⁸F-JK-PSMA-7,经亲核取代、酸水解、高效液相色谱分离、固相萃取等4步合成¹⁸F-JK-PSMA-7,并测定其质量和体外稳定性，计算其脂水分配系数，通过动物实验评价其生物安全性和生物分布特性，同时对1例健康志愿者和3例前列腺癌患者行PET/CT显像。结果表明，¹⁸F-JK-PSMA-7的合成时间为45 min,合成产率为(31.0±2.5)%(未衰减校正，n=3),放化纯度>99%,体外稳定性良好，常温放置3个半衰期放化纯度仍>95%,脂水分配系数logP=-3.56±0.13,其他质控结果满足临床要求。生物分布实验显示其在体内稳定性较好，在所测时间点肌肉和骨骼几乎无摄取，药物在膀胱内的摄取较高，证明其经泌尿系统代谢。对1例健康志愿者和3例前列腺癌患者行PET/CT显像发现：1例健康志愿者主要在唾液腺、泪腺、下颌下腺、肝脏、脾脏和肠道、膀胱等器官有生理性高放射性摄取，3例前列腺癌患者前列腺病灶和转移灶都有浓聚，...

Preparation of 18F- Labeled Prostate Specific Membrane Antigen JK-PSMA-7 and Its Preliminary PET/CT Imaging

A novel ¹⁸F^- labeled prostate specific membrane antigen¹⁸F-JK-PSMA-7 was synthesized, its biodistribution in mice was determined and its preliminary PET/CT imaging was studied. ¹⁸F-JK-PSMA-7 was synthesized through 4 steps of nucleophilic substitution、acid hydrolysis、high performance liquid chromatography separation and solid phase extraction. Its quality and in vitro stability were determined, and lipid-water partition coefficient was calculated. in addition, its biological safety and biological distribution characteristics were evaluated through animal experiments. PET/CT imaging was performed on 1 healthy volunteer and 3 prostate cancer patients. The synthesis time of ¹⁸F-JK-PSMA-7 was 45 min, and the synthesis yield was (31.0±2.5)% (without attenuation correction, n=3), the radiochemical purity was greater than 99%, and other quality control results met the clinical requirements. In vitro stability of the drug was good, and the radiochemical purity was still greater than 95% after 3 half-lives at room temperature, its lipid-water partition coefficient logP was calculated to be equal to -3.56±0.13. Biodistribution experiments of drug showed that it had good stability in vivo, and it was barely concentrated in muscle and bone at the time points measured, but the drug was highly concentrated in the bladder, which proved that it was metabolized by the urinary system. PET/CT imaging of 1 healthy volunteer and 3 prostate cancer patients showed that 1 healthy volunteer had physiologically high uptake mainly in salivary gland, lacrimal gland, submandibular gland, liver, spleen, intestine, bladder. ¹⁸F-JK-PSMA-7 was concentrated in Prostate lesions and metastases of 3 patients with prostate cancer with the maximum standard uptake value (SUVmax) of 54.82. It can be seen that the new prostate-specific membrane antigen imaging agent ¹⁸F-JK-PSMA-7 has high synthetic yield、high radiochemical purity and stable quality, and has the potential to become a new drug for the diagnosis of prostate cancer.