Production of the Auger-electron emitter ¹⁶¹Ho for nuclear medicine using proton beams

Auger-electron emitters have steadily acquired considerable attention in the last decade due to their potential to treat micrometastases. However, the limited availability of Auger-electron emitters has restricted investigations of the radiobiological effects induced by Auger cascades. Among the medically relevant Auger-electron-emitting radiolanthanides, ¹⁶¹Ho stands out as a suitable candidate thanks to its high emission of low-energy electrons. Its low-intensity, low-energy γ rays would enable dosimetry evaluation, while minimizing the deposited dose. This project involved the measurement of proton-induced activation cross sections of holmium radioisotopes, focusing on ^{160m,161cum,162m}Ho, using ^nat,161,162Dy targets irradiated with an 18 MeV cyclotron at the Bern medical cyclotron laboratory. Additionally, production yields were measured at the Paul Scherrer Institute using a 72 MeV separated-sector cyclotron, where dysprosium targets were irradiated for the ¹⁶¹Ho direct production and ¹⁶⁵Ho targets to study the indirect production pathway via ¹⁶¹Er decay. Comparison with previously published experimental data showed good agreement for the production cross sections of relevant holmium radioisotopes, while those of ^160gHo were reported here for the first time. The nuclear reaction cross sections of ^{161cum,162g,162m}Ho were determined by inverting a system of linear equations. Theoretical predictions from the TENDL 2023 library generally overestimated the experimental excitation functions by up to 50%. Irradiation runs of production targets validated the cross sections measured. ¹⁶⁵Ho emerged as optimal target material for large-scale production of highly radionuclidically pure ¹⁶¹Ho. Six-hour irradiation of ¹⁶⁵Ho targets yielded 15 GBq of ¹⁶¹Er's end-of-bombardment activity at up to 99.98% of radionuclidic purity using 45 MeV proton beams.