Comparison between Three Promising ß-emitting Radionuclides, (67)Cu, (47)Sc and (161)Tb, with Emphasis on Doses Delivered to Minimal Residual Disease

Abstract

Purpose: Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy β(-) emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of (67)Cu, (47)Sc and (161)Tb to irradiate small tumors.

Methods: The absorbed dose deriving from a homogeneous distribution of (67)Cu, (47)Sc or (161)Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including β(-) spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm(3), which would result in a dose of 160 Gy if totally absorbed.

Results: The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, (161)Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with (67)Cu, 14.8 Gy with (47)Sc and 44.5 Gy with (161)Tb. Auger and conversion electrons accounted for 71% of (161)Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by (161)Tb was 4.1 times higher than that from (67)Cu and 8.1 times that from (47)Sc.

Conclusion: (161)Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy β(-) emission and low-energy conversion and Auger electrons. Therefore (161)Tb might be a better candidate than (67)Cu and (47)Sc for treating minimal residual disease in a clinical setting.

Keywords: Dose; copper-67; lutetium-177.; micrometastases; minimal residual disease; radionuclide therapy; scandium-47; terbium-161.

Figure 1

Electron emissions of ⁶⁷Cu, ⁴⁷Sc and ¹⁶¹Tb. β-spectra are in red (integral of the curve = 1), conversions electrons (CE) are in blue and Auger electrons (including Coster-Kronig electrons) in green. Conversion and Auger electrons whose probability was <0.0001 were neglected and are not represented.

Figure 2

Electron dose delivered by ⁶⁷Cu, ⁴⁷Sc and ¹⁶¹Tb (considering 1 MeV released per µm³) as a function of sphere size. The maximal value of 160 Gy/MeV/µm³ corresponds to total absorption.

Figure 3

Patterns of energy deposit (keV per MeV released) of ⁴⁷Sc and ¹⁶¹Tb over the first 500 µm around a point source.

Figure 4

Two-dimensional plots of the tracks of two representative conversion electrons and two representative Auger electrons from ¹⁶¹Tb as simulated with CELLDOSE. Panel A reproduces the full path of the two CE (39.9 keV and 17.87 keV). Panel B is a magnification of the paths of Auger electrons (5.25 keV, 1.02 keV). The solid and open circles represent the ionizing interactions induced by the primary and the secondary electrons, respectively.