Targeted radionuclide therapy directed to the tumor phenotypes: A dosimetric approach using MC simulations

Abstract

Background: In Targeted Radionuclide Therapy (TRT), the continuous technological effort in imaging tumor phenotypes (i.e. sub-volumes with different phenotypic characteristics) and in precise radiopharmaceutical tumor-targeting, is allowing for a better dosimetric optimization at the tumor phenotype level. The aim of this study was to evaluate the dosimetric efficiency (considering strategic absorbed dose delivery to the phenotypes) of personalized TRT directed to the tumor phenotypes.

Methods: The dosimetric assessment was performed using a four-phenotype realistic tumor model implemented within the ICRP reference voxel phantom and simulations using the state-of-the-art Monte Carlo program PENELOPE. The dose assessment was performed for five radionuclides commonly used in therapy and/or diagnostic procedures: ¹²⁵I, ^99mTc, ¹⁷⁷Lu, ¹⁶¹Tb and ⁶⁷Ga. Two irradiation scenarios were considered: (i) the Whole Tumor Treatment Planning Scenario (WTTPS), i.e. the four phenotypes irradiated with the same radionuclide; (ii) the Phenotype Treatment Planning Scenario (PTPS), i.e. each phenotype irradiated by a single radionuclide. The optimal radionuclide configurations were studied considering the maximization of the absorbed dose delivered to the tumor and the minimization of dose to healthy tissues.

Results: In WTTPS, ¹²⁵I outperforms the other radionuclides in terms of the ratio of the maximum absorbed dose delivered to the tumor and the minimum absorbed dose delivered to healthy tissues. In the PTPS, the use of ¹⁶¹Tb in combination with the other radionuclides maximizes the absorbed dose in the tumor tissues while simultaneously minimizing dose to healthy tissue, compared to the WTTPS. In agreement with recent pre-clinical studies, our computational results confirm and indicate the beneficial additive dosimetric effects of Auger and conversion electrons of ¹⁶¹Tb with respect to ¹⁷⁷Lu, when considering the same cumulated activity for both. Interestingly, in considering a realistic tumor model, the better dosimetric performances of ¹⁶¹Tb were confirmed also for tumor volumes ranging from 1.98 cm³ to 33.32 cm³.

Conclusions: Dose assessment in realistic non-homogeneous tumor models could provide more insights with respect to consider only homogenous water-spheres tumor models and should be taken into account in dosimetry-based TRT planning studies.

Keywords: Auger-emitting radionuclides; Monte Carlo simulations; S-value; Targeted radionuclide therapy; Tumor phenotype.