^(131)I标记精氨酸-精氨酸-亮氨酸多肽在荷瘤小鼠体内的分布与显像

A novel radioiodinated peptide of arginine-arginine-leucine(RRL) for biodistribution and tumor angiogenic endothelium imaging

目的设计、合成含精氨酸-精氨酸-亮氨酸(RRL)多肽序列,研究131I标记RRL小分子环肽在荷前列腺癌BALB/c裸鼠体内的分布与显像研究。方法通过固相法合成包含RRL序列的10环肽(YCGGRRLGGC)。在多肽序列的两个半胱氨酸之间形成二硫键以维持序列的稳定性。通过高效液相色谱法(HPLC)分析、纯化合成的多肽,并进行电喷雾离子质谱(ESI-MS)分析。通过氯胺-T法进行RRL多肽的131I标记,建立荷PC3前列腺癌BALB/c裸鼠模型,分别进行体内分布和肿瘤显像研究。结果RRL多肽序列被成功合成,HPLC后目标产品纯度99.56%。质谱分析结果显示产物相对分子量为1040kD,与RRL多肽理论分子量一致。RRL多肽131I标记率60%左右,放射化学纯度96.5%。动物体内肿瘤对131I标记的RRL多肽的摄取在注射后明显高于对照肽。注射后3h小鼠甲状腺(未封闭)及腹腔放射性聚集明显,肿瘤部位见少量放射性聚集,在注射后24h小鼠肿瘤及膀胱明显放射性聚集。结论RRL10环肽的设计是成功的,应用氯胺T法对其131I标记是可行的。肿瘤对131I标记化合物的特异性摄取预示着RRL10环肽在肿瘤显像、治疗中拥有很好的应用前景。

Objective To design and synthesize a radioiodinated peptide of arginine-arginine-leucine（RRL） for tumor angiogenic endothelium imaging, and to investigate the biodistribution and imaging of ^131I labeled RRL peptide in human prostate carcinoma bearing nude mice. Methods The 10-mer cyclic peptide contained the RRI. sequence was synthesized （YCG GRRLGGC） with an Apex 396 multiple peptide synthesizer. Disulfide bonds between the cysteines maintained the cyclic structure. The peptide then was purified by high performance liquid chromatography （HPLC）. Radioiodination of the RRL peptides was performed by the chloramine-T method. ^131 I labeled peptides was injected into the nude mice bearing human prostate carcinoma via tail vein. Biodistribution and imaging results in vivo was obtained. Results RRI. sequence was synthesized successfully. HPLC of the crude product yielded a main peak containing 99.56% of the absorbance at 220 nm. The ^131 I labeling rate of RRL peptides was about 60 Y00. The radiochemical purity was 96.5 %. The radiochemical purity of the labeled compound remain 90.3% at 24 h in human blood serum at 37℃. In the biodistribution studies, the ^131I labeled RRL peptide accumulated in the tumor to a higher level than in the other organs. The ^131I labeled RRL peptide could successfully image the tumor in human prostate carcinoma bearing nude mice. Conclusion The results of this study suggestted that radioiodination of RRL peptides is feasible and the labeled compound is stable in human blood serum at 37℃ at 24 h. The ^131 I labeled RRL peptides are valuable to detected tumors as molecular probe.