转移性去势抵抗性前列腺癌治疗药物177Lu-PSMA-3Q与177Lu-PSMA-I&T的对比研究  

Comparative study of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer

作　　者：刘欢欢[1] 张晓军[1] 潘越[1] 张靖峰 孙树伟 张锦明[1] Liu Huanhuan;Zhang Xiaojun;Pan Yue;Zhang Jingfeng;Sun Shuwei;Zhang Jinming(Department of Nuclear Medicine,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心核医学科,北京100853

出　　处：《中华核医学与分子影像杂志》2024年第6期337-342,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

摘　　要：目的:评估177Lu-前列腺特异膜抗原(PSMA)-3Q在转移性去势抵抗性前列腺癌(mCRPC)治疗中的潜力,并与177Lu-PSMA-I&T进行比较。方法:制备177Lu-PSMA-3Q并进行质量控制和稳定性检测;对177Lu-PSMA-3Q、177Lu-PSMA-I&T在正常BALB/c小鼠和22Rv1荷瘤鼠体内进行药代动力学评价及生物分布研究;对2例来自解放军总医院的mCRPC患者(60岁和76岁)分别静脉注射177Lu-PSMA-3Q、177Lu-PSMA-I&T(7.40±0.74)GBq后24、72、120 h进行SPECT显像。采用两独立样本t检验分析数据。结果:制备得到的177Lu-PSMA-3Q总活度为74 GBq,未校正产率为95%,室温放置168 h后放化纯仍大于95%。177Lu-PSMA-3Q和177Lu-PSMA-I&T的分布半衰期分别为(0.75±0.22)和(0.86±0.19)min,清除半衰期分别为(24.74±3.77)和(29.53±3.42)min。正常小鼠生物分布结果示,注射后5 d 177Lu-PSMA-3Q在肝、肺、肾中的摄取值明显低于177Lu-PSMA-I&T(t值:4.24~8.36,均P<0.05)。22Rv1荷瘤鼠生物分布结果示,177Lu-PSMA-3Q在注射后24 h的肿瘤摄取最高,且高于177Lu-PSMA-I&T[(0.856±0.183)与(0.579±0.126)每克组织百分注射剂量率(%ID/g);t=2.78,P=0.024];快速的清除模式使177Lu-PSMA-3Q有着高肿瘤/肌肉比值(99.604±11.106),且明显高于177Lu-PSMA-I&T的摄取比值(45.078±10.444;t=7.80,P<0.001)。在患者SPECT显像中,177Lu-PSMA-3Q和177Lu-PSMA-I&T 120 h的病灶残余计数分别占24 h的0.32±0.04与0.58±0.04,差异有统计学意义(t=7.62,P=0.002)。结论:177Lu-PSMA-3Q标记简便,产率和放化纯高,稳定性好,具有良好的生物学性能,患者体内靶向性好,滞留时间较长,背景清除速率快,是较理想的靶向PSMA的前列腺癌治疗药物。Objective To evaluate the potential of 177Lu-prostate specific membrane antigen(PSMA)-3Q in the treatment of metastatic castration-resistant prostate cancer(mCRPC)and compare it with 177Lu-PSMA-I&T.Methods 177Lu-PSMA-3Q was prepared and the quality control and stability testing were performed.Pharmacokinetic evaluation and biodistribution of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were conducted in normal BALB/c mice and 22Rv1 tumor-bearing mice.SPECT imaging was performed on 2 patients(60 and 76 years old)with mCRPC from Chinese PLA General Hospital at 24,72,and 120 h after injection of 177Lu-PSMA-3Q or 177Lu-PSMA-I&T((7.40±0.74)GBq).Data were analyzed by using independent-sample t test.Results 177Lu-PSMA-3Q was prepared with the total activity of 74 GBq,the yield rate of 95%(uncorrected),and the radiochemical purity was still above 95%after 168 h at room temperature.The distribution half-lives of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T were(0.75±0.22)and(0.86±0.19)min,and the clearance half-lives were(24.74±3.77)and(29.53±3.42)min.Biodistribution of normal mice showed that the uptake values in the liver,lungs,and kidneys 5 d after injection of 177Lu-PSMA-3Q were lower than those of 177Lu-PSMA-I&T(t values:4.24-8.36,all P<0.05).The tumor uptake of 177Lu-PSMA-3Q after 24 h injection was the highest and was higher than that of 177Lu-PSMA-I&T((0.856±0.183)vs(0.579±0.126)percentage activity of injection dose per gram of tissue(%ID/g);t=2.78,P=0.024)in 22Rv1 tumor-bearing mice.The rapid clearance pattern resulted in a higher tumor/muscle(T/M)ratio for 177Lu-PSMA-3Q(99.604±11.106),which was significantly higher than that for 177Lu-PSMA-I&T(45.078±10.444;t=7.80,P<0.001).According to SPECT imaging of patients with mCRPC,the residual lesion counts of 177Lu-PSMA-3Q and 177Lu-PSMA-I&T at 120 h accounted for 0.32±0.05 and 0.58±0.04 of those at 24 h,with significant difference(t=7.62,P=0.002).Conclusion 177Lu-PSMA-3Q is easy to label,and has high yield and radiochemical purity,good stability,excellent biological performance,goo

关 键 词：前列腺肿瘤 前列腺特异膜抗原 同位素标记 镥 放射性核素显像 小鼠 裸 

分 类 号：R737.25[医药卫生—肿瘤]