Comparison of the dosimetry and cell survival effect of 177Lu and 161Tb somatostatin analog radiopharmaceuticals in cancer cell clusters and micrometastases

Background:<bold> </bold>Lu-177-based radiopharmaceuticals (RPs) are the most used for targeted radionuclide therapy (TRT) due to their good response rates. However, the worldwide availability of Lu-177 is limited. Tb-161 represents a potential alternative for TRT, as it emits photons for SPECT imaging, beta(-)-particles for therapy, and also releases a significant yield of internal conversion (IE) and Auger electrons (AE). This research aimed to evaluate cell dosimetry with the MIRDcell code considering a realistic localization of three Tb-161- and Lu-177-somatostatin (SST) analogs in different subcellular regions as reported in the literature, various cell cluster sizes (25-1000 mu m of radius) and percentage of labeled cells. Experimental values of the alpha- and beta-survival coefficients determined by external beam photon irradiation were used to estimate the survival fraction (SF) of AR42J pancreatic cell clusters and micrometastases. Results:<bold> </bold>The different localization of RPs labeled with the same radionuclide within the cells, resulted in only slight variations in the dose absorbed by the nuclei (AD(N)) of the labeled cells with no differences observed in either the unlabeled cells or the SF. AD(N) of labeled cells (MDLC) produced by Tb-161-RPs were from 2.8-3.7 times higher than those delivered by Lu-177-RPs in cell clusters with a radius lower than 0.1 mm and 10% of labeled cells, due to the higher amount of energy emitted by Tb-161-disintegration in form of IE and AE. However, the Tb-161-RPs/Lu-177-RPs MDLC ratio decreased below 1.6 in larger cell clusters (0.5-1 mm) with > 40% labeled cells, due to the significantly higher Lu-177-RPs cross-irradiation contribution. Using a fixed number of disintegrations, SFs of Tb-161-RPs in clusters with > 40% labeled cells were lower than those of Lu-177-RPs, but when the same amount of emitted energy was used no significant differences in SF were observed between Lu-177- and Tb-161-RPs, except for the smallest cluster sizes. Conclusions:<bold> </bold>Despite the emissions of IE and AE from Tb-161-RPs, their localization within different subcellular regions exerted a negligible influence on the AD(N). The same cell damage produced by Lu-177-RPs could be achieved using smaller quantities of Tb-161-RPs, thus making Tb-161 a suitable alternative for TRT.