^(99m)Tc标记的前列腺特异性膜抗原抑制剂HYNIC-P137的制备与临床转化  

Preparation and Clinical Translation Study of ^(99m)Tc-labeled Prostate-Specific Membrane Antigen Inhibitor HYNIC-P137

作　　者：段小江 廖栩鹤[1] 肖迪 张卓晨 张俊波[2] 范岩[1] 杨兴 DUAN Xiaojiang;LIAO Xuhe;XIAO Di;ZHANG Zhuochen;ZHANG Junbo;FAN Yan;YANG Xing(Department of Nuclear Medicine,Peking University First Hospital,Beijing 100034,China;College of Chemistry,Beijing Normal University,Beijing 100875,China)

机构地区：[1]北京大学第一医院核医学科,北京100034 [2]北京师范大学化学学院,北京100875

出　　处：《同位素》2023年第4期389-396,共8页Journal of Isotopes

基　　金：国家自然科学基金资助项目(22106006,92059101,22277002,21877004)。

摘　　要：为开发低膀胱滞留的前列腺癌SPECT显像剂,在68 Ga-P137结构的基础上制备了^(99m)Tc-P137,对其进行临床前评估和初步的临床转化研究。通过固相合成方法制备标记前体HYNIC-P137,用EDDA作为共配体对前体进行^(99m)Tc标记,并对产物^(99m)Tc-P137进行质控。考察^(99m)Tc-P137的脂水分配系数和体外稳定性,考察其在PSMA阳性细胞和阴性细胞上的摄取和抑制。进行正常昆明小鼠的生物分布和荷瘤鼠的SPECT/CT显像,最后进行临床转化研究。结果表明,前体HYNIC-P137的固相合成方便易得,标记产物^(99m)Tc-P137的放化纯度接近100%,体外稳定性好,亲水性较强。正常昆明小鼠生物分布显示,该探针血液清除较快,主要通过肾脏代谢。荷瘤鼠的小动物SPECT/CT显示,^(99m)Tc-P137主要在PSMA阳性肿瘤和肾脏区域浓集,且均可被明显抑制,显示出高度的体内特异性。临床转化显示,^(99m)Tc-P137在膀胱蓄积较低,肝内放射性较高,对前列腺癌原位灶和淋巴结转移均具有良好的检出性能。研究表明,^(99m)Tc-P137有望成为高亲和性、低膀胱滞留的新型三七素类SPECT前列腺癌显像探针。To develop a low bladder accumulation SPECT prostate cancer imaging agent,^(99m)Tc-P137 was prepared on the basis of 68 Ga-P137 structure,and the probe was subjected to detailed preclinical evaluation and preliminary clinical translation studies.The labeled precursor HYNIC-P137 was prepared by solid-phase synthesis method,and the labeled precursor ^(99m)Tc was labeled with EDDA as co-ligand,and the product ^(99m)Tc-P137 was quality controlled.The lipid-water partition coefficient and in vitro stability of ^(99m)Tc-P137 were examined,and its uptake and inhibition on PSMA-positive and negative cells were investigated.Biodistribution in normal Kunming mice and SPECT/CT imaging in hormonal mice were performed,and finally,clinical translation studies were performed.The results showed that the precursor HYNIC-P137 could be easily obtained from solid-phase synthesis,and the labeled product ^(99m)Tc-P137 had a radiochemical purity close to 100%,good in vitro stability and high hydrophilicity.Normal Kunming mouse biodistribution showed rapid blood clearance of this probe,which was mainly metabolized by the kidney.MicroSPECT/CT of tumor-bearing mice showed that ^(99m)Tc-P137 was concentrated mainly in PSMA-positive tumors and renal regions,and both could be significantly inhibited,showing a high degree of intra-specific specificity.Clinical translation showed low accumulation of ^(99m)Tc-P137 in the bladder,high intrahepatic radioactivity,and good detection performance for prostate cancer foci in situ and lymph node metastases.It was shown that ^(99m)Tc-P137 with high affinity and low bladder accumulation is a novel ODAP-based SPECT prostate cancer imaging probe.

关 键 词：前列腺特异性膜抗原 锝-99m 三七素 联肼尼克酰胺 

分 类 号：TL923[核科学技术—核燃料循环与材料] R817.9[医药卫生—影像医学与核医学]