Background: Lung cancer is a malignant tumor with high mortality rates. This study aims to develop potential candidates of integrin αvβ3 imaging agents, which can facilitate the diagnosis and treatment of lung cancer.
Methods: The T7 peptide was labeled with carbonyl technetium. The thin layer chromatography with acetone as the development system was performed to investigate the purity and stability of (99m)Tc-T7. The binding affinity of (99m)Tc-T7 with NCI-H157 tumor cells was determined. The biodistribution of (99m)Tc-T7 in nude mice bearing non-small cell lung carcinoma was observed after injection of (99m)Tc-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 purification, with good stability in vitro. The association and dissociation constant (KD) of (99m)Tc-T7 with NCI-H157 tumor cells was 196.1 nM. (99m)Tc-T7 was mainly metabolism through the internal organs with rapid blood removal. Moreover, the uptake in tumor tissue was significantly higher than the muscle with tumor/muscle ratio of 5.8. In addition, the (99m)Tc-T7 exhibited a transient accumulation in the lungs.
Conclusions: The (99m)Tc-T7 could be prepared using a simple method, had high labeling rate and good stability, and could be accumulated at tumor site. Thus, (99m)Tc-T7 is a potential 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(99m)Tc-T7的放化纯度与稳定性，丙酮作展开系统。测定(99m)Tc-T7与NCI-H157细胞的亲和力。研究(99m)Tc-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。(99m)Tc-T7与NCI-H157细胞的平衡解离常数为196.1 nM。(99m)Tc-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4 h-8 h之间取值较为理想。(99m)Tc-T7在肺内存在一过性聚集。结论 (99m)Tc-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。