Estimation of S-values using the Digimouse phantom for radionuclides commonly under preclinical investigation for treatment of early and terminal stages of hepatocellular cancer

Abstract

Hepatocellular carcinoma (HCC) is a major therapeutic challenge due to its complex biology and the need for targeted radionuclide therapy. This study aims to evaluate and compare the S-values of radionuclides that have been investigated for HCC radionuclide therapy including 131I, 90Y, 188Re, 166Ho, 125I, and 67Cu. Using the InterDosi code version 1.3 in conjunction with the Digimouse voxelized phantom, we calculated S-values for two HCC radionuclide therapy scenarios representing the early and terminal stages of the disease by considering a small tumor in the liver and the whole liver as separate radiation sources. The results highlight significant variations in dose distribution, which affect both therapeutic efficacy and the protection of healthy tissues. Indeed, in the first scenario while the small tumor in the liver is irradiated, both 67Cu and 131I exhibited high S-values, with variations between them of less than 10 %. Notably, 67Cu enabled a substantial reduction in dose absorption in neighboring organs, reducing exposure by 54 %–71 % compared with 131I, making it a safer option for treatment. Whereas, in the second scenario in which the whole liver is irradiated, 90Y and 188Re had the highest S-values, delivering homogeneous doses throughout the liver, but also resulting in higher exposure of surrounding organs. In contrast, 67Cu showed moderate S-values while significantly reducing doses to non-target organs, with kidney exposure reduced by 97.9 % compared to 90Y. We conclude that 67Cu appears to be a promising candidate for optimizing HCC radionuclide therapy minimizing toxicity to healthy tissues while maintaining high radiation therapeutic efficacy.