Preparation of ⁹⁹Tc^m-MAG₃-VEGF_125-136 polypeptide and its biodistribution and imaging in osteosarcoma mice

Objective: To synthesize ⁹⁹Tc^m labeled VEGF fragment (VEGF_125-136) 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: VEGF_125-136 was synthesized by conventional solid phase synthesis method, and directly coupled with MAG₃ to form MAG₃-YEGF_125-136, then MAG₃-VEGF_125-136 was labeled with ⁹⁹Tc^m. The osteosarcoma bearing nude mice were randomly divided into four groups by random number table and studied for ⁹⁹Tc^m-MAG₃-VEGF_125-136 distribution at 0.5, 1, 2, 4 h, respectively. The other 10 osteosarcoma bearing nude mice 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 ⁹⁹Tc^m-MAG₃-VEGF_125-136 was cleared fast in blood and mainly excreted through the kidneys and liver. Tumor uptake of ⁹⁹Tc^m-MAG₃-VEGF_125-136 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), but no significant difference was observed at 0.5 h 1.44, P > 0.05). Conclusion: ⁹⁹Tc^m-MAG₃-VEGF_125-136 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. (authors)