靶向PSMA分子探针Al18F-PSMA-BCH的制备优化及其初步显像研究  

Improvement of Al18F-PSMA-BCH preparation and its preliminary imaging study

作　　者：刘特立 刘辰[1] 夏雷 郭晓轶 蒋金泉 朱华[1] 李囡[1] 王铁[2] 杨志[1] Liu Teli;Liu Chen;Xia Lei;Guo Xiaoyi;Jiang Jinquan;Zhu Hua;Li Nan;Wang Tie;Yang Zhi(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Beijing 100142,China;Nuclear Medicine Department,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科、恶性肿瘤发病机制及转化研究教育部重点实验室,100142 [2]首都医科大学附属北京朝阳医院核医学科,100020

出　　处：《中华核医学与分子影像杂志》2019年第12期743-747,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(81871386);北京市自然科学基金(7194246)。

摘　　要：目的优化靶向前列腺特异膜抗原(PSMA)分子探针Al18F-PSMA-BCH(北京肿瘤医院)的标记方法,研究该探针进行临床试验及临床转化的可行性。方法将无载体的18F-加入到含有标记前体PSMA-BCH、AlCl3和邻苯二甲酸氢钾溶液的反应瓶中,震荡摇匀后110℃加热15 min,经Sep-Pak Light C18柱纯化和0.22μm微孔无菌滤膜过滤,制得Al18F-PSMA-BCH。测定其放化纯和体外稳定性;研究Al18F-PSMA-BCH在5名健康志愿者[年龄:(68±7)岁]体内的生物分布并估算吸收剂量;对1例前列腺癌生化复发患者(65岁)行PET/CT显像研究。结果制得的Al18F-PSMA-BCH未衰变校正的产率为(38.0±3.5)%,放化纯大于99%,比活度为(16.4±4.4)MBq/nmol,在室温生理盐水体系中具有良好的稳定性。在健康志愿者体内,Al18F-PSMA-BCH主要在膀胱、肾脏、泪腺、腮腺和下颌下腺等部位有高摄取,其中肾脏的内照射吸收剂量最高[(152.89±33.43)μGy/MBq],而骨骼中较低[(11.10±1.23)μGy/MBq];健康志愿者的全身有效剂量为(0.0135±0.0025)mSv/MBq。前列腺癌生化复发患者PET/CT显像可见多发骨转移病灶。结论采用邻苯二甲酸氢钾作pH调节剂制备得到的Al18F-PSMA-BCH有用于对前列腺癌诊断、分期和复发监测的潜力。ObjectiveTo optimize the radiolabeling of prostate specific membrane antigen(PSMA)-targeted probe Al18F-PSMA-BCH(Beijing Cancer Hospital)and to evaluate its potential for clinical trial and translation.MethodsThe mixture of PSMA-BCH,AlCl3,potassium biphthalate and no-carrier loaded 18F-was reacted at 110℃for 15 min,then purified by Sep-Pak Light C18 column and filtered through 0.22μm sterile filter to obtain Al18F-PSMA-BCH.The radiolabeled yield and radiochemical purity were determined.Al18F-PSMA-BCH PET/CT imaging was performed on 5 healthy volunteers(age:(68±7)years)for biodistribution and radiation dosimetry estimate and on 1 patient(65 years)with recurrent prostate cancer.ResultsThe non-decay-corrected radiochemical yield of Al18F-PSMA-BCH was(38.0±3.5)%with the radiochemical purity>99%and the specific activity of(16.4±4.4)MBq/nmol.Al18F-PSMA-BCH was stable in saline at room temperature.In healthy volunteers,radioactivity was mainly accumulated in the bladder,kidneys,lacrimal glands,parotid glands and submandibular glands,of which kidneys were the most critical organs with the dosimetry of(152.89±33.43)μGy/MBq,while bones showed lower uptake((11.10±1.23)μGy/MBq)than most organs.The effective dose of whole body was(0.0135±0.0025)mSv/MBq.Multiple bone metastases were observed by Al18F-PSMA-BCH PET/CT imaging in a patient with recurrent prostate cancer.ConclusionsAl18F-PSMA-BCH prepared with the pH controller of potassium biphthalate holds the potential for the diagnosis,staging and monitoring recurrence of prostate cancer.

关 键 词：前列腺肿瘤 前列腺特异膜抗原 同位素标记 氟放射性同位素 正电子发射断层显像术 体层摄影术 X线计算机 

分 类 号：R73[医药卫生—肿瘤]