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[目的]设计与制备131I标记的针对αvβ3受体的通过二硫键成环的RGD肽,研究其在肿瘤中的摄取情况。[方法]根据文献报道的构效关系研究结果设计RGD肽,基于αvβ3受体的胞外区及其配体复合物三维晶体结构,通过分子对接筛选出能量打分最低的多肽结构;采用ChT法进行131I标记,建立荷黑色素瘤动物模型,进行体内分布实验、非标记肽竞争抑制实验及肿瘤显像研究。[结果]c(CRGDYC)具有最低的对接能量,其131I的标记率为90%,放射化学纯度达99%;131I-c(CRGDYC)在肿瘤中有较高的摄取率,且清除缓慢,静脉注射后24h,肿瘤与肌肉(T/M)和肿瘤与血液(T/B)摄取比值分别为6.34与1.1。未标记肽可明显抑制肿瘤对131I-c(CRGDYC)的摄取。静脉注射后1h即可见肿瘤显影,随时间延长,影像逐渐清晰,148h仍可见肿瘤影像。[结论]c(CRGDYC)可被肿瘤组织特异性摄取并有较高的摄取率和较长的滞留时间,有可能应用于肿瘤血管生成显像与肿瘤治疗。
[Objective] To design and prepare 131I-labeled RGD peptides disulfide-bonded to αvβ3 receptor and study their uptake in tumors. [Method] RGD peptides were designed according to the results of structure-activity relationship reported in the literature. Based on the three-dimensional crystal structure of the extracellular domain of αvβ3 receptor and its ligand complex, peptides with the lowest energy score were screened through molecular docking. ChT 131I marker, establish animal model of human melanoma, in vivo distribution experiment, non-labeled peptide competition inhibition experiment and tumor imaging studies. [Result] C (CRGDYC) had the lowest docking energy, the labeling rate of 131I was 90% and the radiochemical purity was 99%. The high uptake rate of 131I-c (CRGDYC) Twenty-four hours after injection, tumor to muscle (T / M) and tumor to blood (T / B) uptake ratios were 6.34 and 1.1, respectively. Unlabeled peptides significantly inhibited tumor uptake of 131I-c (CRGDYC). 1h after intravenous injection can be seen tumor development, with time, the image gradually clear, still visible 148h tumor imaging. [Conclusion] c (CRGDYC) can be specifically uptake by tumor tissue with high uptake rate and long residence time, which may be used in tumor angiogenesis imaging and oncology treatment.