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

Abstract

Objective. The development of alpha-emitting radiopharmaceuticals using 225Ac (t ½ = 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. 226Ac (t ½ = 29.4 h) is a candidate isotope for in vivo imaging of preclinical 225Ac 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 226Ac imaging and presents the first-ever 226Ac 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 <0.85 mm. Significance. Overall, the feasibility of preclinical imaging with 226Ac was demonstrated with quantitative SPECT imaging achieved for both its 158 keV and 230 keV photopeaks. The HEUHR collimator is recommended for imaging 226Ac activity distributions in small animals due to its resolution <0.85 mm. Future work will explore the feasibility of using 226Ac both as an element-equivalent isotope for 225Ac radiopharmaceuticals, or as a standalone therapeutic isotope.