Preparation of 99Tcm-MAG3-VEGF125-136 polypeptide and its biodistribution and imaging in osteosarcoma mice

Objective To synthesize 99Tcm labeled VEGF fragment (VEGF125-136) and evaluate its biodistribution and imaging in the nude mice bearing human osteosarcoma, in order to find a probe to improve the early diagnosis and targeted therapy of osteosarcoma. Methods VEGF125-136 was synthesized by conventional solid phase synthesis method, and directly coupled with MAG3 to form MAG3-VEGF125-136, then MAG3-VEGF125-136 was labeled with 99Tcm. The osteosarcoma bearing nude mice were randomly divided into four groups by random number table and studied for 99Tcm-MAG3-VEGF125-136 distribution at 0.5, 1, 2, 4 h, respectively. The other 10 osteosarcoma bearing nude mices were divided into the experimental group and competitive inhibition group, and underwent radionuclide imaging. The T/NT ratio was calculated. Data were analyzed using two-sample t test. Results The radioactive labeling rate was greater than 95%, radiochemical purity was still greater than 85% after 12 h in room temperature. The 99Tcm-MAG3-VEGF125-136 was cleared fast in blood and mainly excreted through the kidneys and liver. Tumor uptake of 99Tcm-MAG3-VEGF125-136 was highest at 1 h with (0.28±0.02) %ID/g. The T/NT ratios of experimental group at 0.5, 1, 2, 4 h were 1.07±0.10, 3.10±0.19, 2.63±0.14, 1.90±0.09, respectively. In competitive inhibition group, no obvious radioactivity concentration was observed in tumors. The T/NT ratios were 0.99±0.05, 1.06±0.06, 0.98±0.03, 0.97±0.03 at 0.5, 1, 2, 4 h respectively. The T/NT ratios were significantly different between the two groups at 1, 2, 4 h (t=22.52, 26.36 and 22.31, all P 0.05). Conclusion 99Tcm-MAG3-VEGF125-136 has high labeling efficacy, good stability and high specificity to osteosarcoma. It can be used as an agent for early diagnosis and therapy monitoring in osteosarcoma. Key words: Vascular endothelial growth factors; Mercaptoacetyltriglycine; Isotope labeling; Technetium; Osteosarcoma; Radionuclide imaging; Mice, nude