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

OBJECTIVE Rhenium is one of the most valuable elements for internal radiotherapy because (186)Re and (188)Re have favorable physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of (186/188)Re. Labeling methods that use bifunctional chelating agents such as MAG3 require the conjugation of the (186/188)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 (186/188)Re-labeled antibody. For this purpose, we selected (186/188)Re(I) tricarbonyl complex as a chelating site. In this study, A7 (an IgG1 murine monoclonal antibody) was used as a model protein. (186/188)Re-labeled A7 was prepared by directly reacting a (186/188)Re(I) tricarbonyl precursor, [(186/188)Re(CO)(3)(H(2)O)(3)](+), with A7. We then compared the biodistribution of (186/188)Re-labeled A7 in tumor-bearing mice with (125)I-labeled A7. METHODS For labeling A7, [(186/188)Re(CO)(3)(H(2)O)(3)](+) was prepared according to a published procedure. (186/188)Re-labeled A7 ((186/188)Re-(CO)(3)-A7) was prepared by reacting [(186/188)Re(CO)(3)(H(2)O)(3)](+) with A7 at 43 degrees C for 2 h. Biodistribution experiments were performed by the intravenous administration of (186/188)Re-(CO)(3)-A7 solution into tumor-bearing mice. RESULTS (186)Re-(CO)(3)-A7 and (188)Re-(CO)(3)-A7 were prepared with radiochemical yields of 23 and 28%, respectively. After purification with a PD-10 column, (186/188)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 (186)Re-(CO)(3)-A7 and (188)Re-(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 (125)I-A7 in the tumor was almost the same as that of (186/188)Re-(CO)(3)-A7 at 24-h postinjection. Blood clearances of (186/188)Re-(CO)(3)-A7 were faster than those of (125)I-A7. CONCLUSION (186/188)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.