The preparation of 99Tcm-J591 and its SPECT imaging of nude mice bearing human prostate cancer / 中华核医学与分子影像杂志

ABSTRACT

Objective To study the binding performance of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody J591 (99Tcm-J591) and prostate cancer cells in vitro,the biodistribution and SPECT imaging of 99Tcm-J591 in nude mice bearing human prostate cancer in vivo.Methods The monoclonal antibody J591 was labeled with 99Tcm by improved Schwarz method.Labeled antibody was purified by Sephadex G-50.The labeling efficiency and radiochemical purity were measured by paper chromatography and trichloroacetic acid method.The binding performance of J591 and prostate cancer cells was measured by flow cytometry in vitro.The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts served as experiment group,mice bearing PSMA-negative PC3 tumors served as control group.6.2-8.5 MBq of 99Tcm-J591 (25 μg) was intravenously injected into mice.Gamma imaging was performed 2,6,12 and 24 h after injection,T/NT was calculated by ROI technique.After scanned 12 h post injection,4 mice of the experiment group and 5 mice of the control group were sacrificed and the tracer in vivo biodistribution was measured by gamma-counting,and the ％ ID/g was calculated.Two-sample t test was carried out to validate significant difference of ％ID/g between two groups.Results The labeling efficiency and radiochemieal purity of 99Tcm-J591 were (78.9±6.2)％ and (92.3±5.1)％,respectively,and the specific activity of 99Tcm-J591 was 68.7 MBq/mg.The antibody J591 and 99Tcm-J591 could strongly combine with PSMA-positive C4-2 cells in vitro,and didn't combine with PSMA-negative PC3 cells in vitro.SPECT imaging results showed that radioactive concentration was obvious in tumor 6 h post injection,the concentration scope became large and the tumor image was clear 12 h post injection.T/NT was 1.9±1.1 at 2 h,4.3±1.8 at 6 h,5.6±2.7 at 12 h,1.4±0.6 at 24 h,respectively.In the control group,no radioactivity concentration was found in tumor,and T/NT was less than 2.The biodistribution results showed that ％ID/g of tumor tissue was 20.1±5.2 in the experiment group and 5.8±2.6 in the control group,and there was significant difference (t=5.37,P＜0.001).No significant tracer uptake occurred in other tissues and organs between the two groups (all t＜ 1.98,all P＞0.05).Conclusion The immunoactivity,characteristics of biodistribution and tumor targeting property of monoclonal antibody J591 show promising future and potential values in diagnosis and therapy of prostate cancer.