Al^(18)F-PSMA-11的制备及其PET/CT显像的初步应用

Preparation of Al^(18)F-PSMA-11 and its preliminary PET/CT imaging

目的优化前列腺特异膜抗原(PSMA)靶向分子探针Al^(18)F-PSMA-11的制备条件和方法,研究该探针临床转化的可行性。方法PSMA-N,N′-双[2-羟基-5-(羧乙基)苄基]乙二胺-N,N′-二乙酸(HBED-CC)溶于CH3COONH4缓冲液(pH=4.8)中,与溶于纯水的AlCl_(3)·3H_(2)O按照物质的量比1∶1于60℃反应10 min,经tC18柱纯化并冻干制成[Al]-PSMA-11。用^(18)F-标记[Al]-PSMA-11,考察反应温度和pH值对标记率的影响。标记产物经tC18柱纯化和无菌滤膜过滤制得Al^(18)F-PSMA-11。对比Al^(18)F-PSMA-11与68Ga-PSMA-11在5名健康志愿者[年龄(56±8)岁]的体内分布,采用两独立样本t检验比较2组SUV_(max)的差异。对1例前列腺癌根治术后生化复发患者(70岁)行Al^(18)F-PSMA-11 PET/CT早期及延迟显像以评估其对前列腺癌复发监测的潜力。结果Al^(18)F-PSMA-11在pH=4.8,60℃水相中反应15 min的标记率为(42.3±3.2)%,tC18柱纯化后产品室温放置3 h后的放化纯仍大于95%。Al^(18)F-PSMA-11与68Ga-PSMA-11体内分布基本一致,主要浓聚在泪腺、腮腺、颌下腺、肝脏、脾脏、肾脏、膀胱及部分肠道,且2组各主要靶器官的SUV_(max)差异均无统计学意义(t值:0.19~1.95,均P>0.05)。前列腺癌生化复发患者的Al^(18)F-PSMA-11延迟显像(注射后3 h)可见多发骨转移灶。结论采用[Al]-PSMA-11预螯合的方法合成的Al^(18)F-PSMA-11可以满足临床PET显像应用,对前列腺癌转移灶有良好的定位和显像潜能。

Objective To optimize the preparation conditions and methods of Al^(18)F-prostate specific membrane antigen(PSMA)-11 and evaluate the feasibility of clinical transformation.Methods PSMA-N,N′-bis(2-hydroxy-5-(carboxyethy)benzyl)ethylenediamine-N,N′-diacetic acid(HBED-CC)dissolved in CH3COONH4 buffer(pH=4.8)was reacted with AlCl_(3)·3H_(2)O dissolved in pure water at a molar ratio of 1∶1(60℃,10 min),and then purified by tC18 column and freeze-dried to obtain[Al]-PSMA-11.[Al]-PSMA-11 was labeled by ^(18)F-and the effects of reaction temperature and pH value on the labeling rate were investigated.The labeled products were purified by tC18 column and filtered through sterile filter to obtain Al^(18)F-PSMA-11.The comparison of biodistribution between Al^(18)F-PSMA-11 and 68Ga-PSMA-11 was analyzed on 5 healthy volunteers(age(56±8)years).The differences of SUV_(max)between two groups were analyzed by independent-sample t test.Besides,the early and delayed imaging of Al^(18)F-PSMA-11 PET/CT were performed on a patient(70 years old)with recurrent prostate cancer for assessment of its potential for prostate cancer recurrence monitoring.Results The labeling rate was(42.3±3.2)%reacting in aqueous phase(60℃,pH=4.8)for 15 min.After being purified with tC18 cartridge,the radiochemical purity of the product was still more than 95%after placement at room temperature for 3 h.Preliminary application demonstrated that there was no significant difference in the biodistribution of Al^(18)F-PSMA-11 and 68Ga-PSMA-11 among lacrimal gland,parotid gland,submandibular gland,liver,spleen,kidney,bladder and part of intestine and SUV_(max)of targeted organs were also not different(t values:0.19-1.95,all P>0.05)between two groups.Multiple bone metastases were observed by Al^(18)F-PSMA-11 PET/CT delayed imaging(3 h)in a patient with recurrent prostate cancer.Conclusion Al^(18)F-PSMA-11 produced with pre-conjugated[Al]-PSMA-11 meets the requirement of the PET imaging application,and it has good potential of localization and imaging for prostate cancer metastatic lesions.