碘标APRPGY多肽与肿瘤新生血管亲和性的实验研究

Experimental study of affinity of radioiodine labeling APRPGY peptide for tumor angiogenesis

探讨放射性碘标记APRPGY肽在体内与肿瘤新生血管的亲和特性。氯胺-T法对APRPGY肽行碘-131标记,并分析标记物放化纯;ICR小鼠创伤愈合模型和HepA实体瘤模型小鼠尾静脉注射131I-APRPGY(174kBq/只),并于不同时间断颈处死小鼠,取各脏器或组织,称重,测cpm,计算%ID/g等(n=6)。标记物放化纯为95.5%,并在24h内保持基本稳定;动物体内分布显示,131I-APRPGY在血、肾中分布较多,且组织清除速度较快,主要以肾脏排泄;肿瘤组织中的131I-APRPGY在注射后10min达6.7%ID/g,至240min时降为2.1%ID/g,在5、10、30、60、120、240min时分别为肌肉的2.1、6.2、4.7、3.3、3.5、3.2倍;131I-APRPGY的创伤愈合组织与肌肉的放射性比在10、30、60、120和240min时分别为0.8、1.3、1.8、1.9和1.4。131I-APRPGY能较好地浓聚于实体瘤组织,在创伤愈合组织中也相对浓聚,证实131I-APRPGY与肿瘤新生血管有较强的亲和性,经进一步修饰,有可能获得靶向肿瘤新生血管的显像药物。

The purpose is to investigate the characteristics of APRPGY peptide labeled with radioiodine homing to tumor angiogenesis. The preparation of radioiodinated APRPGY was carried out by Ch-T method. Radiochemical purity was determined by the paper chromatographic system. Biodistribution studies were accomplished using wound healing model and tumor bearing model ICR mice. At 5, 10, 30, 60, 120 and 240 min after radiopharmaceutical administration （174 kBq/200 μL of ^131I-APRPGY）, the animals were sacrificed. Blood samples and other interested tissues were collected, weighted and counted （n=6 animals each time）. The percent injected dose per gram of organ （%ID/g） and the ratio of tumor/muscle for each animal were calculated. The radiochemical purity of the ^131I-APRPGY was above 95%. The biodistribution of the radiolabeled peptide showed higher levels in both blood and kidneys than in other tissues. In all other organs, the radioactivity was rapidly excreted mainly by kidneys. The accumulation of radioactivity in the tumor was 6.7 %ID/g at 10 min and decreased within 240 min to 2.1%ID/g. The ratios of tumor/muscle of ^131I-APRPGY were 2.1, 6.2, 3.3, 3.5 and 3.2 at 5, 10, 60,120 and 240 min, respectively. In wound healing model, the ratios of wound-healing tissue/muscle were 0.8, 1.3, 1.8, 1.9 and 1.4 at 10, 30, 60,120 and 240 min, respectively. The high specific tumor uptake and predominantly renal excretion make ^131I-APRPGY a potential candidate for tumor angiogenesis imaging. This peptide is therefore worthy of further investigation.