Dose Deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy

Abstract

Radiopharmaceutical therapy, traditionally limited to refractory metastatic cancer, is being increasingly used at earlier stages, such as for treating minimal residual disease. The aim of this study was to compare the effectiveness of ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb at irradiating micrometastases. ⁹⁰Y and ¹⁷⁷Lu are widely used β⁻-emitting radionuclides. ¹⁶¹Tb is a medium-energy β⁻ radionuclide that is similar to ¹⁷⁷Lu but emits a higher percentage of conversion and Auger electrons. ¹¹¹In emits γ-photons and conversion and Auger electrons. Methods: We used the Monte Carlo code CELLDOSE to assess electron doses from a uniform distribution of ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, or ¹⁶¹Tb in spheres with diameters ranging from 10 mm to 10 μm. Because these isotopes differ in electron energy per decay, the doses were compared assuming that 1 MeV was released per μm³, which would result in 160 Gy if totally absorbed. Results: In a 10-mm sphere, the doses delivered by ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb were 96.5, 152, 153, and 152 Gy, respectively. The doses decreased along with the decrease in sphere size, and more abruptly so for ⁹⁰Y. In a 100-μm metastasis, the dose delivered by ⁹⁰Y was only 1.36 Gy, compared with 24.5 Gy for ¹⁷⁷Lu, 38.9 Gy for ¹¹¹In, and 44.5 Gy for ¹⁶¹Tb. In cell-sized spheres, the dose delivered by ¹¹¹In and ¹⁶¹Tb was higher than that of ¹⁷⁷Lu. For instance, in a 10-μm cell, ¹⁷⁷Lu delivered 3.92 Gy, compared with 22.8 Gy for ¹¹¹In and 14.1 Gy for ¹⁶¹Tb. Conclusion: ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb might be more appropriate than ⁹⁰Y for treating minimal residual disease. ¹⁶¹Tb is a promising radionuclide because it combines the advantages of a medium-energy β⁻ emission with those of Auger electrons and emits fewer photons than ¹¹¹In.