SPECT imaging of 226Ac as a theranostic isotope for 225Ac radiopharmaceutical development

Objective. The development of alpha-emitting radiopharmaceuticals using Ac-225 (t (1/2) = 9.92 d) benefits from the quantitative determination of its biodistribution and is not always easy to directly measure. An element-equivalent matched-pair would allow for more accurate biodistribution and dosimetry estimates. Ac-226 (t (1/2) = 29.4 h) is a candidate isotope for in vivo imaging of preclinical Ac-225 radiopharmaceuticals, given its 158 keV and 230 keV gamma emissions making it suitable for quantitative SPECT imaging. This work aimed to conduct a performance assessment for Ac-226 imaging and presents the first-ever Ac-226 SPECT images. Approach. To establish imaging performance with regards to contrast and noise, image quality phantoms were scanned using a microSPECT/CT system. To assess the resolution, a hot rod phantom with cylindrical rods with diameters between 0.85 and 1.70 mm was additionally imaged. Two collimators were evaluated: a high-energy ultra-high resolution (HEUHR) collimator and an extra ultra-high sensitivity (UHS) collimator. Images were reconstructed from two distinct photopeaks at 158 keV and 230 keV. Main results. The HEUHR SPECT image measurements of high activity concentration regions were consistent with values determined independently via gamma spectroscopy, within 9% error. The lower energy 158 keV photopeak images demonstrated slightly better contrast recovery. In the resolution phantom, the UHS collimator only resolved rods >= 1.30 mm and >= 1.50 mm for the 158 keV and 230 keV photopeaks, respectively, while the HEUHR collimator clearly resolved all rods, with resolution Significance. Overall, the feasibility of preclinical imaging with Ac-226 was demonstrated with quantitative SPECT imaging achieved for both its 158 keV and 230 keV photopeaks. The HEUHR collimator is recommended for imaging Ac-226 activity distributions in small animals due to its resolution <0.85 mm. Future work will explore the feasibility of using Ac-226 both as an element-equivalent isotope for Ac-225 radiopharmaceuticals, or as a standalone therapeutic isotope.

Automated summary

This study evaluated the performance of Ac-226 imaging using quantitative SPECT imaging and presented the first-ever Ac-226 SPECT images. The results showed the feasibility of preclinical imaging with Ac-226, which demonstrated high resolution. The HEUHR collimator was recommended for imaging the activity distribution of Ac-226 in small animals.