Image-Based Dosimetry in Targeted Radionuclide Therapy with Terbium-161: From Technical Foundations to Clinical Application

Abstract

This work explores SPECT/CT-based quantification of the novel therapeutic radionuclide terbium-161 (161Tb). The interest in 161Tb stems from its substantial emission of low-energy conversion and Auger electrons, hypothesized to enhance the treatment of microscopic cancer disease. In Paper I, technical aspects of 161Tb imaging were investigated through phantom studies, demonstrating the feasibility of accurate quantification. A medium-energy collimator combined with a 75 keV ± 10% energy window was found preferable, which was attributed to reduced degradation from dead time, septal penetration, and scatter. These effects were further examined in Paper II through characterization of a clinical SPECT/CT system, confirming that 161Tb imaging is particularly susceptible to dead-time effects, owing to the emission of high-intensity X-rays and penetration from high-energy, low-yield γ-photons. These limitations were mitigated by employing a medium-energy collimator, rather than a low-energy one. In Papers III and IV, quantitative 161Tb SPECT/CT imaging was applied in two first-in-human clinical studies, evaluating novel 161Tb-labeled radioligands for neuroendocrine and prostate cancer, respectively. In both studies, initial dosimetry results indicated favorable therapeutic indices compared to clinically available 177Lu-labeled alternatives. Together, these studies underscore both the limitations and potential of 161Tb SPECT/CT imaging, contributing to the groundwork for its future clinical implementation.