SPECT imaging of Ac-226 for radiopharmaceutical development: performance evaluation as a theranostic isotope pair for Ac-225

Introduction: The development of alpha-emitting radiopharmaceuticals using ²²⁵Ac (t_½ = 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 (t_½ = 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.

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