^(177)Lu-DOTA-TATE治疗晚期转移性神经内分泌瘤的辐射剂量学、药代动力学和安全性评估  

Radiation dosimetry,pharmacokinetics and safety evaluation of^(177)Lu-DOTA-TATE in the treatment of advanced metastatic neuroendocrine tumors

作　　者：董彦良 张靖峰 韩蕴 孙树伟 徐白萱[2] Dong Yanliang;Zhang Jingfeng;Han Yun;Sun Shuwei;Xu Baixuan(Imaging Medicine and Nuclear Medicine,Chinese PLA Medical School,Beijing 100853,China;Department of Nuclear Medicine,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军医学院影像医学与核医学专业,北京100853 [2]解放军总医院第一医学中心核医学科,北京100853

出　　处：《国际放射医学核医学杂志》2023年第12期738-745,共8页International Journal of Radiation Medicine and Nuclear Medicine

基　　金：国家自然科学基金(82071958)。

摘　　要：目的评估^(177)Lu-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(^(177)Lu-DOTA-TATE)治疗晚期转移性神经内分泌瘤(NETs)的辐射剂量学、药代动力学和安全性。方法前瞻性分析2021年7月至2022年3月于解放军总医院第一医学中心经组织病理学检查结果确诊的6例晚期转移性NETs患者,其中男性4例、女性2例,年龄(50.2±9.6)岁。给予患者静脉注射^(177)Lu-DOTA-TATE,单次给药剂量为(7400±740)MBq,最多给药4个周期,每个周期间隔(8±1)周。由于疫情影响导致^(177)LuCl_(3)原料供应困难,因此仅3例患者接受了完整的4个周期治疗,1例患者接受了3个周期治疗和2例患者接受了1个周期治疗后退出研究。分析^(177)Lu-DOTA-TATE在患者体内的分布和代谢情况,计算辐射剂量学、药代动力学等相关参数,并进行安全性随访。接受辐射剂量学及药代动力学研究的患者在首次给药后不同时间点采集SPECT图像、血液样本以及尿液样本。计量资料的比较采用配对样本t检验。结果3例NETs患者完成了辐射剂量学研究,^(177)Lu-DOTA-TATE的吸收剂量由大到小依次为肿瘤病灶>肾脏>脾脏>肝脏。3例患者同时完成了药代动力学研究,达峰浓度(C_(max))均值为16.61μg/L,从0时至最后1个可定量浓度的血药浓度-时间曲线下面积(AUC_(0-t))均值为57.11μg/(L·h),从0时外推到无穷的血药浓度-时间(AUC_(0-∞))均值为76.25μg/(L·h),表观分布容积(V_(z))均值为222.55 L,清除率(CL)均值为3.44 L/h,分布相的半衰期(T_(1/2α))均值为0.89 h,消除相的半衰期(T_(1/2β))均值为48.94 h。^(177)Lu-DOTA-TATE主要经肾脏代谢,患者体内药物在给药后48 h内累积排泄率为61.05%。6例患者接受^(177)Lu-DOTA-TATE治疗后安全性随访期均未发生严重不良事件,治疗前后血常规、血生化、凝血功能、尿常规等检查指标差异均无统计学意义(t=−1.437~1.378,均P>0.05)。结论^(177)Lu-DOObjective To evaluate the radiation dosimetry,pharmacokinetics,and safety of^(177)Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotate(^(177)Lu-DOTA-TATE)in the treatment of advanced metastatic neuroendocrine tumors(NETs).Methods A prospective analysis was performed for 6 patients with advanced metastatic NETs diagnosed by histopathological examination in the First Medical Center of PLA General Hospital from July 2021 to March 2022,including 4 males and 2 females,aged(50.2±9.6)years old.Patients were given intravenous injection of^(177)Lu-DOTA-TATE at a single dose of(7400±740)MBq for up to 4 cycles,with each cycle interval of(8±1)weeks.Considering the difficulties in the supply of^(177)LuCl_(3) raw materials owing to pandemic,only 3 patients received a full 4 cycles of treatment,1 patient received 3 cycles treatment and 2 patients received 1 cycles treatment and then withdrew from the study.The distribution and metabolism of^(177)Lu-DOTA-TATE in patients were analyzed,and the related parameters such as radiation dosimetry and pharmacokinetics were calculated,safety follow-up was also carried out.Patients undergoing radiation dosimetry and pharmacokinetic studies were subjected to SPECT images,blood samples,and urine samples at different time points after the first dose.Paired-sample t-test was used to compare the measured data with normal distribution and homogeneity of variance.Results The dosimetry study of^(177)Lu-DOTA-TATE was completed in 3 patients with NETs.The absorbed dose of^(177)Lu-DOTA-TATE decreased in the following order:focus>kidney>spleen>liver.Three patients completed the pharmacokinetics study at the same time;the average calculated peak concentration(C_(max))was 16.61μg/L,and the average concentration time AUC(AUC_(0-t))from zero to the last quantifiable concentration was 57.11μg/(L·h).The average value of AUC(AUC_(0-∞))extrapolated from zero to infinity was 76.25μg/(L·h),the average apparent volume of distribution(Vz)was 222.55 L,the average cleara

关 键 词：镥 奥曲肽 神经内分泌瘤 辐射剂量 受体 生长抑素 药物代谢动力学 

分 类 号：R739.4[医药卫生—肿瘤]