Preparation of 99Tcm-MAG3-VEGF125-136 polypeptide and its biodistribution and imaging in osteosarcoma mice / 中华核医学与分子影像杂志

ABSTRACT

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),but no significant difference was observed at 0.5 h (t =1.44,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.