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

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.

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.

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.

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.

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.