99mTc标记T7肽及其在裸鼠非小细胞肺癌模型体内的生物分布研究

摘要

Background and objective Lung cancer is a malignant tumor with high mortality rates. hTis study aims to develop potential candidates of integrinαvβ3 imaging agents, which can facilitate the diagnosis and treatment of lung cancer. Methods hTe T7 peptide was labeled with carbonyl technetium. hTe thin layer chromatography with acetone as the development system was performed to investigate the purity and stability of 99mTc-T7. hTe binding affnity of 99mTc-T7 with NCI-H157 tumor cells was determined. hTe biodistribution of 99mTc-T7 in nude mice bearing non-small cell lung carci-noma was observed atfer injection of 99mTc-T7 at 0.5 h, 1 h, 2 h, 4 h, and 8 h, and the radioactive ratio of tumor (T) and non-tumor tissues (NT) was calculated. Results 99mTc labeled T7 had high radiochemical purity of more than 90%, which does not require further puriifcation, with good stability in vitro. hTe association and dissociation constant (KD) of 99mTc-T7 with NCI-H157 tumor cells was 196.1 nM. 99mTc-T7 was mainly metabolism through the internal organs with rapid blood removal. Moreover, the uptake in tumor tissue was signiifcantly higher than the muscle with tumor/muscle ratio of 5.8. In addition, the 99mTc-T7 exhibited a transient accumulation in the lungs. Conclusion hTe 99mTc-T7 could be prepared using a simple method, had high labeling rate and good stability, and could be accumulated at tumor site. hTus, 99mTc-T7 is a poten-tial lung cancer SPECT/CT imaging agent.%背景与目的肺癌是一种死亡率极高的恶性肿瘤，针对肺癌的早期诊断和治疗有着重要的意义和价值，本研究旨在探讨羰基锝法标记的肿瘤抑素T7肽用作裸鼠肺癌早期显像剂的初步研究。方法采用羰基锝法标记T7肽，薄层色谱法检测99mTc-T7的放化纯度与稳定性，丙酮作展开系统。测定99mTc-T7与NCI-H157细胞的亲和力。研究99mTc-T7于0.5 h、1 h、2 h、4 h、8 h在荷人非小细胞肺腺癌裸鼠体内的生物分布特性，并计算肿瘤（T）与非肿瘤组织（NT）放射性比值。结果99mTc对T7肽标记率高，放化纯度达90%以上，不需进一步纯化，体外稳定性好。99mTc-T7与NCI-H157细胞的平衡解离常数为196.1 nM。99mTc-T7在裸鼠体内主要通过内脏器官代谢，血液清除较快，在肿瘤部位有一定程度聚集，肿瘤/肌肉比值随时间延长而增加，可达到5以上，在4h-8h之间取值较为理想。99mTc-T7在肺内存在一过性聚集。结论99mTc-T7制备方法简便，标记率高，稳定性好，并能在肺癌肿瘤部位聚集，有望用作肺癌SPECT/CT显像剂。