Biodistribution and dosimetry for combined [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging

Purpose Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for Ac-225-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [Lu-177]Lu-PSMA-I & T/[Ac-225]Ac-PSMA-I & T treatment.Methods Eight prostate cancer patients (1000 MBq/8 MBq [Lu-177]Lu-PSMA-I & T/[Ac-225]Ac-PSMA-I & T) received a single-bed quantitative Lu-177/Ac-225 SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head a 3.5 min, 128 x 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny Bi-213 was imaged along with the peak at 208 keV (width: 15%) of Lu-177. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40-45 mm was employed to match the signal-to-noise ratio of Ac-225 and Lu-177, respectively.Results Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [Lu-177]Lu-PSMA-I & T and [Ac-225]Ac-PSMA-I & T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [Ac-225]Ac-PSMA-I & T (2.5 +/- 0.8 vs. 2.1 +/- 0.9), while for [Lu-177]Lu-PSMA-I & T lesion SUV were significantly higher (p = 0.03; 1.8 +/- 1.1 vs. 2.1 +/- 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found.Conclusion Quantitative low-count SPECT imaging of the peak at 440 keV during [Ac-225]Ac-PSMA-I & T therapy is feasible. Multi-isotope imaging for [Lu-177]Lu-PSMA-I & T/[Ac-225]Ac-PSMA-I & T therapy indicates accumulation of free Bi-213 in the kidneys.