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

Abstract

Objective: The development of alpha-emitting radiopharmaceuticals using 225Ac (t½=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 (t½=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 – 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.

In vivo quantitative SPECT imaging of actinium-226: feasibility and proof-of-concept

“…226 Ac production and activity quantification TRIUMF (Vancouver, Canada) produces 226 Ac with its Isotope Separation Accelerator (ISAC) facility using the isotope separation on-line (ISOL) method (Dilling et al 2014). This production method is briefly described here and is presented in further detail in Koniar et al (2022a). 480 MeV protons are bombarded on a uranium carbide target resulting in many spallation products that are extracted as an ion beam and mass separated for atomic number A = 226.…”

“…The UHS collimator is optimized for low energy photons (<350 keV) with high sensitivity which is ideal for imaging low activity concentrations. Previous assessment of this collimator in a phantom study demonstrated its capabilities for 226 Ac SPECT imaging, resolving rod with diameters ⩾1.30 mm in a hot rod phantom (Koniar et al 2022a). Additionally, scans of a contrast phantom yielded up to 94% quantitative accuracy of activity measurements compared to values determined independently by gamma spectroscopy.…”

“…These underlying assumptions require further validation for many theranostic pairs (Miller et al 2022). Lastly, 226 Ac (t 1/2 = 29.4 h) has been proposed as diagnostic counterpart for 225 Ac radiopharmaceuticals, forming an element-equivalent matched pair (Koniar et al 2022a, 2022b, Nelson et al 2023. This method is advantageous for direct detection and maintaining identical chemical properties to 225 (Crawford et al 2018).…”

“…Additionally, 226 Ac could be leveraged as a therapeutic isotope due to its four alpha emissions following the decay of 226 Th (Alfassi et al 2006, Morgenstern et al 2008, Fassbender and Mastren 2019, Ferrier et al 2020, Mastren et al 2020. Previous work has established the capabilities and limitations of 226 Ac SPECT imaging via resolution, contrast, and uniformity phantoms with a small animal microSPECT/-CT scanner (Koniar et al 2022a).…”

Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

“…An alternative approach may be to implement an element equivalent matched pair for imaging. Thereby, Ac-226 may be an option when working with Ac-225 to allow further investigation of the biodistribution and dosimetry, for example (Koniar et al 2022 ). Currently, to our knowledge, this research is within the preliminary phase.…”