Preparation and evaluation of 186 / 188 Re -

Objective: Rhenium is one of the most valuable elements for internal radiotherapy because Re and Re have favorable physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of Re. Labeling methods that use bifunctional chelating agents such as MAG3 require the conjugation of the Re 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-labeled antibody. For this purpose, we selected Re(I) tricarbonyl complex as a chelating site. In this study, A7 (an IgG1 murine monoclonal antibody) was used as a model protein. Re-labeled A7 was prepared by directly reacting a Re(I) tricarbonyl precursor, [Re(CO)3(H2O)3], with A7. We then compared the biodistribution of Re-labeled A7 in tumor-bearing mice with I-labeled A7. Methods: For labeling A7, [Re(CO)3(H2O)3] was prepared according to a published procedure. Re-labeled A7 (Re-(CO)3-A7) was prepared by reacting [Re(CO)3(H2O)3] with A7 at 43oC for 2 hours. Ogawa et al. Page 4/29 Biodistribution experiments were performed by the intravenous administration of Re-(CO)3-A7 solution into tumor-bearing mice. Results: Re-(CO)3-A7 and Re-(CO)3-A7 were prepared with radiochemical yields of 23% and 28%, respectively. After purification by a PD-10 column, Re-(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-(CO)3-A7 and Re-(CO)3-A7, respectively, accumulated in the tumor 24 hours postinjection, and the tumor-to-blood ratios were over 2.0 at the same timepoint. Meanwhile, uptake of I-A7 in the tumor was almost the same as those of Re-(CO)3-A7 at 24 hours postinjection. Blood clearances of Re-(CO)3-A7 were faster than that of I-A7. Conclusion: Re-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.