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

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for <jats:sup>225</jats:sup>Ac-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 [<jats:sup>177</jats:sup>Lu]Lu-PSMA-I&T/[<jats:sup>225</jats:sup>Ac]Ac-PSMA-I&T treatment.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Eight prostate cancer patients (1000 MBq/8 MBq [<jats:sup>177</jats:sup>Lu]Lu-PSMA-I&T/[<jats:sup>225</jats:sup>Ac]Ac-PSMA-I&T) received a single-bed quantitative <jats:sup>177</jats:sup>Lu/<jats:sup>225</jats:sup>Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny <jats:sup>213</jats:sup>Bi was imaged along with the peak at 208 keV (width: 15%) of <jats:sup>177</jats:sup>Lu. 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 <jats:sup>225</jats:sup>Ac and <jats:sup>177</jats:sup>Lu, respectively.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Kidney (<jats:italic>r</jats:italic> = 0.96, <jats:italic>p</jats:italic> < 0.01) and lesion (<jats:italic>r</jats:italic> = 0.94, <jats:italic>p</jats:italic> < 0.01) SUV for [<jats:sup>177</jats:sup>Lu]Lu-PSMA-I&T and [<jats:sup>225</jats:sup>Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (<jats:italic>p</jats:italic> < 0.01) for [<jats:sup>225</jats:sup>Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [<jats:sup>177</jats:sup>Lu]Lu-PSMA-I&T lesion SUV were significantly higher (<jats:italic>p</jats:italic> = 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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Quantitative low-count SPECT imaging of the peak at 440 keV during [<jats:sup>225</jats:sup>Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [<jats:sup>177</jats:sup>Lu]Lu-PSMA-I&T/[<jats:sup>225</jats:sup>Ac]Ac-PSMA-I&T therapy indicates accumulation of free <jats:sup>213</jats:sup>Bi in the kidneys.</jats:p> </jats:sec>