Labelled angiostatin with 131I and observed its antitumor effect on nude mice xenografts.

Abstract Objective To purify angiostatin from human plasma, label it with 131I; to observe the therapeutic effects of 131I-angiostatin on transplanted A549 lung carcinoma in nude mice and investigate the clinical prospect of 131I-angiostatin for solid tumor. Methods Salvage angiostatin from human plasma through limited proteolysis by elastase, and purify it by L-Lysine-Sepharose 4B affinity chromatograph, and labeled angiostatin with 131I using method of conventional Iodogen and assessed in labeling efficiency, specific activity and in vitro stability. 32 male nude mice (the mean diameter of tumors transplanted into the right forelimbs was about 1cm )whose forelimbs were transplanted with A549 lung carcinoma were treated with 131I-angiostatin (131I 11.1MBq per mouse, angiostatin 12.5mg/Kg), 131I(11.1 MBq per mouse),angiostatin(12.5mg/Kg)respectively and with similar normal saline (NS) 0.3mL as control. Each drug was given intraperitoneally and injected for four times at an interval of 7 days respectively.The volume of tumors was measured during 28 days after treatment. Results The labeling efficiency ranged from 77.8% to 86.7%, the specific activity could reach up to 1.28~3.96MBq/ug. The radiochemical purity of 131I –Angiostatin reduced to 72% after 7 days in vitro storage (-20℃). The mean volume of transplanted tumors in the mice with A549 lung carcinoma was （1956±98mm3）、（5284±123mm3）、（3948±115mm3）、（7350±153mm3）after treated with 131I –angiostatin, 131I, angiostatin and NS respectively.Conclusions The conventional Iodogen method was a high efficiency iodination of angiostatin, and the labeling efficiency, specific activity and in vitro stability were good.131I –angiostatin can inhibit the growth of transplanted of A549 lung carcinoma in mice, and its inhibitive effect is better than 131I or angiostatin.So it is suggested that 131I –angiostatin has potential prospect of clinical application in the treatment of solid tumor.