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,good targeting ability in patients,longer retention time,and fast background clearance rate,which is an ideal prostate cancer treatment drug targeting PSMA.
作者
刘欢欢
张晓军
潘越
张靖峰
孙树伟
张锦明
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)
出处
《中华核医学与分子影像杂志》
CAS
CSCD
北大核心
2024年第6期337-342,共6页
Chinese Journal of Nuclear Medicine and Molecular Imaging
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
Prostatic neoplasms
Prostate-specific membrane antigen
Isotope labeling
Lutetium
Radionuclide imaging
Mice,nude
