Quantitative SPECT imaging of 225 Ac and its daughters in mice in vivo

Background Targeted alpha therapy (TAT) using actinium‐225 ( 225 Ac) holds great promise for cancer treatment, and to advance 225 Ac therapy it is required to develop accurate dosimetry method. 225 Ac daughters, especially 213 Bi, may redistribute and cause renal toxicity. Currently, direct imaging of 225 Ac‐emitted photons at low injected activity levels remains a technical challenge for image‐based 225 Ac dosimetry. Purpose This study aims to assess the feasibility and accuracy of quantitative in vivo SPECT/CT imaging for 225 Ac and its decay daughters at activity levels similar to those in small animal studies. Methods A state‐of‐the‐art commercial preclinical SPECT/CT scanner was used to image healthy nude mice in vivo and ex vivo after injection of unlabeled 225 Ac from the United States Department of Energy isotope program, at activities below 48.8 kBq. Each in‐vivo imaging was 1.5 h and ex‐vivo imaging was 12 h, at approximately 2 h after injection of 225 Ac, and all SPECT images were reconstructed at multi‐energy windows (82, 218, and 440 keV). Mouse‐like phantom imaging for 1 h at 0.078 MBq and 12 h at 0.496 MBq were also performed to validate quantitative accuracy. Results In vivo SPECT/CT images clearly showed abundant liver uptake, and significant kidney uptake was also observed in 440 keV images for 213 Bi, consistent with known renal toxicity from daughter redistribution. However, quantitative analysis of in vivo, ex vivo, and low‐activity phantom images revealed suboptimal quantitative accuracy, with high background recovery coefficients and variations in measured activity across the energy windows. Conclusions We demonstrated the ability to image 225 Ac and its daughters in vivo at low activity levels. However, the quantitative results confirmed that, even with the state‐of‐the‐art preclinical SPECT/CT system, current methods and reconstruction algorithms may not provide sufficient accuracy for accurate dosimetry at typical activity used in small animal studies.