RT Journal Article SR Electronic T1 SPECT imaging of Ac-226 for radiopharmaceutical development: performance evaluation as a theranostic isotope pair for Ac-225 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 2341 OP 2341 VO 63 IS supplement 2 A1 Koniar, Helena A1 Rodriguez-Rodriguez, Cristina A1 Radchenko, Valery A1 Yang, Hua A1 Kunz, Peter A1 Uribe, Carlos A1 Rahmim, Arman A1 Schaffer, Paul YR 2022 UL http://jnm.snmjournals.org/content/63/supplement_2/2341.abstract AB 2341 Introduction: The development of alpha-emitting radiopharmaceuticals using 225Ac (t½ = 9.9 d) requires quantitative determination of its biodistribution. SPECT imaging of the 225Ac decay chain is possible with its progeny isotopes, 221Fr (218 keV) and 213Bi (440 keV); however, the initial 225Ac decay does not release any imageable emissions. Moreover, injected activities of 225Ac are low resulting in very few gamma detections from 221Fr and 213Bi unless imaging is performed for a very long time. An element-equivalent matched-pair would allow for more accurate biodistribution and dosimetry estimates, and this quantitative pharmacokinetic information can be used to optimize the therapeutic properties of a preclinical radiopharmaceutical. 226Ac (t½ = 29 h) is a candidate isotope for in vivo imaging of preclinical 225Ac-radiopharmaceuticals, given its element-equivalence and its emission of gammas (158 keV and 230 keV); suitable for quantitative SPECT imaging. Furthermore, 226Ac holds promise as a therapeutic isotope as its decay chain consists of four high-energy alpha emissions. This work aimed to conduct a performance assessment for 226Ac-imaging and presents the first-ever 226Ac SPECT images.Methods: Though the current availability of 226Ac may be limited, TRIUMF (Vancouver, Canada) can produce small but suitable quantities of this isotope with its isotope separation on-line (ISOL) facility. For this study, a total of 33.79±0.36 MBq of 226Ac was produced and made available for subsequent imaging studies. Radioactive composition and activity were determined via gamma spectroscopy. To establish the performance of 226Ac-imaging with regards to contrast and noise, image quality phantoms were scanned using the VECTor microSPECT/PET/CT (MILabs, Netherlands). To assess the resolution, a hot rod phantom containing clusters of thin rods with diameters ranging between 0.85 mm and 1.70 mm was additionally imaged. Machine performance was evaluated with two collimators: 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 using the VECTor’s pixel-based ordered subset expectation maximization (POSEM) iterative reconstruction algorithm (16 subsets, 3 iterations). Scatter correction was performed using a triple energy window method and attenuation correction performed by co-registration with CT images. Quantitative SPECT images were obtained via calibration factors determined for each collimator and photopeak combination. Images were also rebinned to 20%, 5%, and 1% of the total counts to assess image quality at lower counting statistics.Results: Activity concentrations observed in the high activity regions of the images were within 11% of values determined independently via gamma spectroscopy. Contrast recovery between the hot-warm regions was highest for the HEUHR collimator with values of 99.3–100.1% compared to 86.6–92.9% for the UHS collimator. Compared to the 230 keV photopeak reconstruction, the lower energy 158 keV photopeak 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. The HEUHR collimator resolved all rods for both 158 keV and 230 keV reconstructed images. Furthermore, when images were reconstructed with 20%, 5%, and 1% of the total counts, the HEUHR collimator maintained resolvability for all rods. Conclusions: The feasibility of preclinical imaging with 226Ac was demonstrated. Quantitative image reconstruction was achieved for both its 158 keV and 230 keV photopeaks. The HEUHR collimator is expected to be most useful 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 unto itself.