The pharmacokinetics and tumor uptake of 125I-recombinant Human plasminogen kringle 5

Objective: To establish the method of 125I-labeled recombinant human plasminogen kringle 5 (rhK5), analyze the pharmacokinetics of rhK5 in rats receiving single injection of vein, obtain the biodistribution data from human lung cancer-bearing Bab1/C nude mice. Methods: rhK5 was 125I labeled using the Iodogen method, the radiochemical purity of 125I-K5 was determined by HPLC. Detect the function of 125I-K5 binding to endothelial cells by competition binding study, Assay the bioactivity of 125I-K5 by MTT. 125I-K5 was injected via caudal vein at the dose of 4μg/kg respectively in rats(n=6). Blood samples were collected at different time, then record the radioactivity and analyze the pharmacokinetics parameters according to the 3p87 program. 125I-K5 was also injected via caudal vein at the dose of 4μg/kg in human lung cancer-bearing Bab1/C nude mice(n=12), then collected blood and tissues samples at different time, recoded the radioactivity and analyzed the biodistribution data. Results: The labeling rate of 125I-K5 was above 80%, radiochemical purity was above 95% and which was also above 95% after stored at 40 degree C for 100 hours. Competition binding studies showed a dose-dependent inhibition of 125I-K5 binding to endothelial cells (ECV304) by excess unlabeled K5. MTT showed the proliferation of ECV304 was inhibited by 125I-K5 at ED50 4μ g/ml. The pharmacokinetics of 125I-K5 in rats was in correspondence with two-compartment-model, The T1/2(α) was 0.31±0.03 h, T1/2(β) was 14.48±0.73 h and AUC was 436.58±34.6(ng/ml)*h. Biodistribution data showed high uptake in the thyroid gland,kidneys, stomach, liver and lungs. Tumor uptake was respectively 3.84±0.21, 2.39±0.11, 1.94±0.13, 1.48±0.09%ID/g at 2 h, 4 h, 8 h and 12 h after injection. Tumor to muscle count ratio increased from 2.56±0.11 at 2 h to 3.21±0.28 at 8 h, 4.94±0.89 at 12 h. Conclusion: 125I-K5 prepared with Iodogen had high purity and stability, the bioactivity was accordant with unlabeled K5. Half-lives in rats received single injection of vein was about 15 h. The tumor high uptake 125I-K5 by virtue of specially binding to endothelial cells, which was the basis of target therapy for tumor.The accumulation of 125I-K5 in the tumor lay the foundation for the imaging diagnosis. (authors)