Distribution Of 13ll-angiostatin And Radioreceptorimaging In Lewis Lung Cancer Bearing Mice

Angiogenesis ,from pre-existing capillary sprouting new blood vessel , is a fundamental process in vivo ,and it's also an important manner in keeping the stability and integrity of the body and maintaining the function of tissue or organism .Angiogenesis ,as a multi-step process ,is under strict control in vivo ,which is carried out by a lot of paracrine factor of polypeptide .The balance between positive and negative regulation determines the switch of angiogenesis .Tumor is a kind of disease of malignant hyperplasia ,characteristic of sustained and active angiogenesis. Many studies demonstrated that tumor growth and metastasis depend on angiogenesis .To get its acquired blood vessel supply ,tumor can secret a lot of angiogenic factors. At the same time, some tumors were proved to be able to produce angiogenesis inhibitors ,such as angiostatin and endostatin, which were derived from plasminogen and collagenXVIII respectively ,two pre-existing protein in vivo . Angiostatin is a 38kD protein purified from serum and urine of tumor bearing mice , it comprises the first four kringle of plasmiongen . Present research data suggest that proteolysis of plasmiongen is a fundamental pattern of anti-angiogenic fragments releasing from plasmiongen.In our experiment , human plasminogen was purified from human plasma by affinity chromatograph ,and then in situ digestion of plasminogen by elastase was carried out to produce angiostatin fragments. Labeled angiostatin with131! using method of conventional chloramines T(CH-T) and lodogen ,131I-angiostatin was assessed in labeling efficiency, specific activity, bioactivity and in vivo stability .After angiostatin was labeled with I3II by the conventional chloramines T (Ch-T) method ,it was injected into C-57 mice bearing Lewis lung cancer . The biodistribution of 13II-Angiostatin and whole body ECT imaging were studied at various intervals after injection .Using the method of CH-T: the labeling efficiency ranged from 71.2 % to 81.7 % ,the specific activity could reach up to 1.24-2.83 TBq ?g"1. Using the method of lodogen: the labeling efficiency ranged from 77.8 % to 86.7 % , the specific activity could reach up tol.28 ?3.96 TBq ?g"'.The radiochemical purity of 131I -angiostatin reduced to 68%(CH-T) and 70% (lodogen) after 7 days in vivo storage (-20 癈). I31I-AG could inhibit the growth of bovine aortic endothelial cells. The %ID/g were 12.48 ,18.56 and 23.17 for tumor and 7.04 ,5.47 and 1.73 for liver at 48 ,96 ,144 hours postinjection respectively . The T/NT ratios were 1.77 , 3.39 and 13.39 for liver at 48 ,96 and 144 hours postinjection respectively . The tumor showed clearly at 96 hours afterinjection .The quality of tumor imaging was relevant to the T/NT ratio .The human angiostatin was prepared by elastase hydrolyzed and purified by L-lysine-Sepharose 4B affinity chromatograph. The conventional lodogen method had a high efficiency iodination of angiostatin, and the labelling effect,specific activity,bioactivity and in vivo stability were higher. The results demonstrated that the 131I-Angiostatinhas specifically bind to the receptor on the suffers of the endothelial cells in the tumor and may also possess the capability of leading to the lung cancer tissue .