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 ¹⁸⁶Re and ¹⁸⁸Re have favorable physical characteristics. However, there are problems when proteins such as antibodies are used as carriers of ^186/188Re. Labeling methods that use bifunctional chelating agents such as MAG3 require the conjugation of the ^186/188Re 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 ^186/188Re-labeled antibody. For this purpose, we selected ^186/188Re(I) tricarbonyl complex as a chelating site. In this study, A7 (an IgG1 murine monoclonal antibody) was used as a model protein. ^186/188Re-labeled A7 was prepared by directly reacting a ^186/188Re(I) tricarbonyl precursor, [^186/188Re(CO)₃(H₂O)₃]⁺, with A7. We then compared the biodistribution of ^186/188Re-labeled A7 in tumor-bearing mice with ¹²⁵I-labeled A7.

For labeling A7, [^186/188Re(CO)₃(H₂O)₃]⁺ was prepared according to a published procedure. ^186/188Re-labeled A7 (^186/188Re-(CO)₃-A7) was prepared by reacting [^186/188Re(CO)₃(H₂O)₃]⁺ with A7 at 43°C for 2 h. Biodistribution experiments were performed by the intravenous administration of ^186/188Re-(CO)₃-A7 solution into tumor-bearing mice.

¹⁸⁶Re-(CO)₃-A7 and ¹⁸⁸Re-(CO)₃-A7 were prepared with radiochemical yields of 23 and 28%, respectively. After purification with a PD-10 column, ^186/188Re-(CO)₃-A7 showed a radiochemical purity of over 95%. In biodistribution experiments, 13.1 and 13.2% of the injected dose/g of ¹⁸⁶Re-(CO)₃-A7 and ¹⁸⁸Re-(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 ¹²⁵I-A7 in the tumor was almost the same as that of ^186/188Re-(CO)₃-A7 at 24-h postinjection. Blood clearances of ^186/188Re-(CO)₃-A7 were faster than those of ¹²⁵I-A7.

^186/188Re-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.