177Lu-PSMA-I&T自动放射标记和临床前前列腺癌靶向研究

中华核医学与分子影像杂志 Pub Date : 2019-11-25 DOI:10.3760/CMA.J.ISSN.2095-2848.2019.11.006

Lulu Zhang, Fan Qiu, Pengjun Zhang, Zhihong Xu, Ting Bu, S. Zang, Shuyue Ai, Feng Wang

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引用次数: 0

摘要

目的用自动化模块合成177lu -前列腺特异性膜抗原(PSMA)-I&T，评价其在小鼠体内的生物分布和药代动力学，研究其对人前列腺癌细胞LNCaP克隆FGC的靶向性。方法采用iQS-TS自动模组对177Lu-PSMA-I&T进行标记。采用高效液相色谱法测定放射线化学纯度和稳定性。在正常ICR小鼠中观察其生物分布，在LNCaP克隆FGC荷瘤小鼠中进行U-SPECT/CT成像。采用独立样本t检验对数据进行分析。结果177Lu-PSMA-I&T在体外和体内稳定，放射标记率为(91.5±4.9)%，放射化学纯度为bb0 99%。177Lu-PSMA-I&T结合LNCaP克隆FGC细胞的半数最大抑制浓度(IC50)为(26.74±3.53)nmol/L。LNCaP克隆FGC细胞对177Lu-PSMA-I&T的摄取随时间增加而增加，添加抑制剂后显著降低(t值:4.301 ~ 27.483，均P<0.05)。177Lu-PSMA-I&T从血液中迅速清除，主要由肾脏排出。在肿瘤中观察到明显的放射性摄取，保留时间长。结论177Lu-PSMA-I&T具有良好的生物学特性，对前列腺癌细胞具有良好的亲和力和靶向性，是一种潜在的治疗前列腺癌的放射性药物。关键词:前列腺肿瘤;前列腺特异性膜抗原;同位素标记;镏;化学合成;肿瘤细胞，培养;老鼠,裸体

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177Lu-PSMA-I&T automated radiolabeling and preclinical prostate cancer targeting research

Objective To synthesis 177Lu-prostate specific membrane antigen (PSMA)-I&T with automated module, evaluate the biodistribution and pharmacokinetics in mice and study the targeting property in human prostate cancer cell line LNCaP Clone FGC. Methods The iQS-TS automated module was applied in labeling 177Lu-PSMA-I&T. Radiochemical purity and stability were determined with high performance liquid chromatography (HPLC). The biodistribution was observed in normal ICR mice and U-SPECT/CT imaging was performed in LNCaP Clone FGC tumor-bearing mice. Independent-sample t test was used to analyze the data. Results 177Lu-PSMA-I&T was stable in vitro and in vivo, with the radiolabeled yield of (91.5±4.9)% and radiochemical purity >99%. The half maximal inhibitory concentration (IC50) of 177Lu-PSMA-I&T binding to LNCaP Clone FGC cells was (26.74±3.53) nmol/L. The uptake of 177Lu-PSMA-I&T by LNCaP Clone FGC cells increased with time and significantly decreased after the inhibitor addition (t values: 4.301-27.483, all P<0.05). 177Lu-PSMA-I&T was cleared from blood rapidly and predominantly excreted by kidneys. Significant radioactive uptake was observed in tumors with a long retention time. Conclusion 177Lu-PSMA-I&T can be produced in a convenient and efficient procedure using iQS-TS automated module, with good biological properties and excellent affinity and targeting property towards prostate cancer cells, which making it a potential radiopharmaceutical for prostate cancer therapy. Key words: Prostatic neoplasms; Prostate-specific membrane antigen; Isotope labeling; Lutetium; Chemical synthesis; Tumor cells, cultured; Mice, nude

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来源期刊

中华核医学与分子影像杂志核医学，分子影像

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发文量

5088

期刊介绍： Chinese Journal of Nuclear Medicine and Molecular Imaging (CJNMMI) was established in 1981, with the name of Chinese Journal of Nuclear Medicine, and renamed in 2012. As the specialized periodical in the domain of nuclear medicine in China, the aim of Chinese Journal of Nuclear Medicine and Molecular Imaging is to develop nuclear medicine sciences, push forward nuclear medicine education and basic construction, foster qualified personnel training and academic exchanges, and popularize related knowledge and raising public awareness. Topics of interest for Chinese Journal of Nuclear Medicine and Molecular Imaging include: -Research and commentary on nuclear medicine and molecular imaging with significant implications for disease diagnosis and treatment -Investigative studies of heart, brain imaging and tumor positioning -Perspectives and reviews on research topics that discuss the implications of findings from the basic science and clinical practice of nuclear medicine and molecular imaging - Nuclear medicine education and personnel training - Topics of interest for nuclear medicine and molecular imaging include subject coverage diseases such as cardiovascular diseases, cancer, Alzheimer’s disease, and Parkinson’s disease, and also radionuclide therapy, radiomics, molecular probes and related translational research.