Shixian Du, Kondapa Naidu Bobba, Robin Peter, Grant T Gullberg, Robert R Flavell, Javier Caravaca, Youngho Seo
We demonstrated the ability to image 225Ac 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.
BACKGROUND: Targeted alpha therapy (TAT) using actinium-225 (225Ac) holds great promise for cancer treatment, and to advance 225Ac therapy it is required to develop accurate dosimetry method. 225Ac daughters, especially 213Bi, may redistribute and cause renal toxicity. Currently, direct imaging of 225Ac-emitted photons at low injected activity levels remains a technical challenge for image-based 225Ac dosimetry.
PURPOSE: This study aims to assess the feasibility and accuracy of quantitative in vivo SPECT/CT imaging for 225Ac 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 225Ac 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 225Ac, 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 213Bi, 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 225Ac 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.