Nuclide Imaging Of Tumor Using Angiogenesis-targeting Agents Labelled With ～(131)I In Tumor-bearing Nude Mice

Background and Objectives The early detection, diagnosis and treatment of the cancer are important for curing of them. Neovascularization is critical for supporting the rapid growth of solid tumors beyond 1–2 mm in diameter and for tumor metastasis. Theαv integrins and vascular endothelial growth factor receptors (VEGFR) are upregulated in proliferating tumor vascular endothelial cells. But,they are seldom expressed in mature vascular endothelial cells of normal organ.Thus,the highly expressed receptor may be useful in tumor early diagnosis and targeted therapy. The ligands specific binding to Theαv integrins and VEGFRS were screened by the phage-displayed libraries.We selected these ligands and labelled them with 131I. Then,we observed them in radionuclide imaging of tumor early diagnosis.Methods Tumor angiogenesis-targeting agents(RGD10,F56,K237) were labeled with the Iodogen method and subsequently separated with Sep-Pak C18 column.Then,their immunoreactive fraction and affinity constants were determined.At last, Their specific distributaion in nude mice bearing human A549 lung adenocarcinoma were observed and compared by eZ-scope.Results The immunoreactive fractions of 131I-RGD10,131I-F56 and 131I-K237 were 42.7%,55.1% and 44.5%. Their affinity constants with HUVEC were 9.41×107L/mol,3.87×107L/mol and 5.98×107L/mol,respectively. 131I- RGD10 was accumulated in tumor more densely than 131I-F56 and 131I-K237 after their injection into the tail vein of nude mice.Conclusion 131I-RGD10 may be useful as a angiogenesis-targeting agent in radionuclide imaging of tumor for early diagnosis. Background and Objective Monoclonal antibody may be not a good radionuclide imaging agent because it cannot penetrate deeply into tumor tissue owing to its large size. Theαv integrins are upregulated in tumor tissue and proliferating tumor vascular endothelial cells. But, they are seldom expressed in mature vascular endothelial cells of normal organ.The tumor angiogenesis-targeting agent(RGD10) specifically binding to theαv integrins was screened to be a molecule imageology agent. Tumor radionuclide imaging of 131I- RGD10 was performed by SPECT and eZ-scope and the biodistribution of 131I- RGD10 was detected in nude mice bearing human A549 lung adenocarcinoma after 131I- RGD10 was injected into the tail vein of nude mice.Methods The nude mice bearing human A549 lung adenocarcinoma model was established. Tumor radionuclide imaging after intravenous injection of 131I- RGD10 was performed by SPECT and eZ-scope and the biodistribution of 131I- RGD10 was detected in nude mice bearing human A549 lung adenocarcinoma.Results The tumor was shown clearly during 5 to 8 hours after 131I- RGD10 was injected into the tail vein of nude mice.The ratio of tumor/lung and tumor/muscle were 3.2 and 4.9.Conclusion All the results indicate that 131I-RGD10 is specifically localized in tumor lesions of nude mice. 131I-RGD10 may be a useful agent in detection of lung carcinoma.