A quantitative study of radionuclide characteristics for radioimmunotherapy from 3D reconstructions using serial autoradiography

Abstract

Purpose: Using 131I-labeled monoclonal antibody (MoAb) data, assess the dosimetrical impact of labeling the same MoAb with 186Re or 90Y, under the assumption that the biodistribution of the radiolabeled MoAb in tumor relative to blood is independent of the radionuclide.

Methods and materials: Radial radioactivity and dose-rate distributions at 1, 4, and 7 days postinjection were derived from three dimensional (3D) reconstructions of serial autoradiographs of LS174T human colon cancer xenografts in athymic nude mice treated with a single intraperitoneal administration of 300 microCi 131I-labeled MoAb 17-1A. Bone marrow dose was calculated taking into account energy deposited external to the bone marrow cavity due to the range of the beta particles.

Results: For 1 cm diameter tumors, uptake was mostly at the tumor surface for earlier postinjection times, but exhibited comparable activity levels from the surface to the core of the 7-day sample. The computed dose-rate distributions for 186Re and 90Y were more uniform than for 131I, but smaller fractions of the dose were deposited within the tumor volume due to the larger mean energies of 90Y and 186Re beta particles relative to those for 131I. However, when the tumor doses were normalized to the production of equivalent bone marrow doses, in the case of athymic nude mice, the tumor doses were calculated to be 15.3 Gy (131I), 14.1 Gy (186Re), and 12.0 Gy (90Y). For comparison, these calculations were extended to the case of human therapy, yielding tumor doses of 16.7 Gy (131I), 18.2 Gy (186Re), and 13.4 Gy (90Y).

Conclusion: In the case of colon cancer xenografts where the MoAb uptake is initially concentrated at the tumor surface, we find a decreasing tumor dose per constant bone marrow dose for radionuclides of increasing mean beta energies and decreasing half-lives. However, a radionuclide with larger mean beta energy such as 90Y generates a significantly more uniform dose deposition within the tumor, especially concerning the core of the tumor, compared to 131I. For human therapy, a gamma component adds little to the tumor dose but increases dose to the marrow.