Preparation and evaluation of 186/188Re-labeled antibody (A7) for radioimmunotherapy with rhenium(I) tricarbonyl core as a chelate site

Rhenium is one of the most valuable elements for internal radiotherapy because Re-186 and Re-188 have favorable physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of Re-186/188. Labeling methods that use bifunctional chelating agents such as MAG3 require the conjugation of the Re-186/188 complex to protein after radiolabeling with the bifunctional chelating agent. These processes are complicated. Therefore, we planned the preparation by a simple method and evaluation of a stable Re-186/188-labeled antibody. For this purpose, we selected Re-186/188(I) tricarbonyl complex as a chelating site. In this study, A7 (an IgG1 murine monoclonal antibody) was used as a model protein. Re-186/188-labeled A7 was prepared by directly reacting a Re-186/188(I) tricarbonyl precursor, [Re-186/188(CO)(3)(H2O)(3)](+), with A7. We then compared the biodistribution of Re-186/188-labeled A7 in tumor-bearing mice with I-125-labeled A7. For labeling A7, [Re-186/188(CO)(3)(H2O)(3)](+) was prepared according to a published procedure. Re-186/188-labeled A7 (Re-186/188-(CO)(3)-A7) was prepared by reacting [Re-186/188(CO)(3)(H2O)(3)](+) with A7 at 43A degrees C for 2 h. Biodistribution experiments were performed by the intravenous administration of Re-186/188-(CO)(3)-A7 solution into tumor-bearing mice. Re-186-(CO)(3)-A7 and Re-188-(CO)(3)-A7 were prepared with radiochemical yields of 23 and 28%, respectively. After purification with a PD-10 column, Re-186/188-(CO)(3)-A7 showed a radiochemical purity of over 95%. In biodistribution experiments, 13.1 and 13.2% of the injected dose/g of Re-186-(CO)(3)-A7 and Re-188-(CO)(3)-A7, respectively, accumulated in the tumor at 24-h postinjection, and the tumor-to-blood ratios were over 2.0 at the same time point. Meanwhile, uptake of I-125-A7 in the tumor was almost the same as that of Re-186/188-(CO)(3)-A7 at 24-h postinjection. Blood clearances of Re-186/188-(CO)(3)-A7 were faster than those of I-125-A7. Re-186/188-labeled A7 showed high uptakes in the tumor. However, further modification of the labeling method would be necessary to improve radiochemical yields and their biodistribution.