^(99m)锝标记前列腺癌PSMA适配体的制备和临床前研究  

Preparation and Preclinical Study of ^(99m)Tc-labeled Prostate Cancer Aptamer

作　　者：杨婷[1] 焦举[1] 吕殷婷 邹琼[1] 曹素娥[1] 江淑琴 张勇[1] 

机构地区：[1]中山大学附属第三医院核医学科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2017年第6期848-853,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省科技计划项目(2013B021800083;2014A020212153);广东省自然科学基金(2015A030313106);教育部博士点基金(20130171110081);广东省医学科研基金(B2014147)

摘　　要：【目的】构建^(99m)Tc标记前列腺癌特异性膜抗原(PSMA)适配体(A10-3.2),并探讨其在体内外的生物特点。【方法】通过双功能螯合剂6-肼基烟酸琥珀酰亚胺酯盐酸盐(SHNH)对适配体A10-3.2进行^(99m)Tc标记(^(99m)Tc-SHNH-A10-3.2),并检测其在体外的稳定性,被前列腺癌LNCa P细胞(PSMA+)摄取的特异性,在移植瘤小鼠体内SPECT/CT成像及生物分布的特点。【结果】所构建^(99m)Tc-SHNH-A10-3.2的标记率和放化纯分别为(71.31±6.78)%和97.03%。^(99m)Tc-SHNH-A10-3.2对PSMA(+)的前列腺癌LNCa P细胞具有明显的靶向特异性,摄取率明显高于PSMA(-)的前列腺癌PC3细胞(P<0.01),在移植瘤体内具有一定的靶向特异性和较高的瘤/肌肉比值。【结论】成功构建^(99m)Tc标记的靶向PSMA的适配体A10-3.2,具有良好的体内外稳定性和靶向性,在小鼠体内具有较高的瘤组织/肌肉本底的比值,显示^(99m)Tc标记的适配体A10-3.2可能是一种具有潜力的PSMA阳性前列腺癌分子靶向显像剂。【Objective】To radiolabel the PSMA aptamer A10-3.2 with ^(99m)Tc, and explore its biological characteristics in vivoand in vitro.【Methods】Using Succinimidyl 6-hydrazinonicotinate hydrochloride(SHNH) as the bifunctional chelating agent to labelaptamer A10-3.2 with ^(99m)Tc, then tested for the stability in vitro, the specific uptake by prostate cancer LNCa P cells(PSMA+), thecharacteristics of SPECT/CT imaging and biodistribution in LNCa P tumor-bearing NOD/SCID mice.【Results】The labeling rate andradiochemical purity of the products( ^(99m)Tc-SHNH-A10-3.2) are(71.31±6.78)% and 97.03%,respectively. ^(99m)Tc-SHNH-A10-3.2 had obvious target specificity for PSMA positive prostate cancer LNCa P cells, its uptake rate was significantly higher than PSMA nega-tive PC-3 cells(P<0.01). And in tumor-bearing mice, the tumor has a certain uptake and a high ratio of the tumor tissue to the mus-cle.【Conclusion】This study successfully constructed ^(99m)Tc-labeled PSMA-targeted aptamer A10-3.2, which has a good stability andtargeting in vivo and in vitro, has a high tumor tissue/muscle ratio in tumor-bearing mice, which show that it may be a potential target-ed molecular imaging agent for prostate cancer.

关 键 词：前列腺癌 前列腺特异性膜抗原 适配体 锝 SPECT/CT显像 

分 类 号：R817.1[医药卫生—影像医学与核医学]