Monte Carlo Comparison of Some beta- Isotopes of Interest for Targeted Radionuclide Therapy of Small Tumors: 177Lu, 67Cu, 47Sc and 161Tb

Objectives The importance of targeted radionuclide therapy is steadily increasing, and its prospective uses now include minimal residual disease. Besides lutetium-177, three other medium-energy beta- emitters, copper-67, scandium-47 and terbium-161, are promising candidates for arming novel radiopharmaceuticals. The aim of this study was to compare the effectiveness of these isotopes at irradiating small tumor volumes.

Methods Electron dose from uniform isotope distributions was assessed with the Monte Carlo code CELLDOSE in spheres of various sizes (from 10mm down to 10µm). All electron emissions, including beta- spectra, Auger and conversion electrons were included. As 177Lu, 67Cu, 47Sc and 161Tb differ in electron energy per decay, doses were compared assuming 1 MeV released per µm3, which would result in 160 Gy if totally absorbed.

Results In a 10-mm sphere, the four isotopes yielded similar dose deposits per MeV/µm3 (152-157 Gy). Dose deposits declined along with the decrease in sphere size, underscoring the difficulty of irradiating micrometastases. 161Tb, however, delivered a higher dose compared to the other isotopes. For instance, in a 100-µm metastasis, dose deposits were 24.5Gy with 177Lu, 24.1Gy with 67Cu, 14.8Gy with 47Sc and 44.5Gy with 161Tb. Auger and conversion electrons accounted for 71% of 161Tb dose. The difference between isotopes further increased when considering spheres of cell-size dimensions.

Conclusions Terbium-161 can effectively target micrometastases and single tumor cells thanks to its decay spectrum that combines medium-energy beta- emission and low-energy conversion and Auger electrons. These results are in agreement with some recent studies on cell cultures and tumor xenografts.