Biodistribution and dosimetry for combined [(177)Lu]Lu-PSMA-I&T/[(225)Ac]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 (225)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 [(177)Lu]Lu-PSMA-I&T/[(225)Ac]Ac-PSMA-I&T treatment. METHODS: Eight prostate cancer patients (1000 MBq/8 MBq [(177)Lu]Lu-PSMA-I&T/[(225)Ac]Ac-PSMA-I&T) received a single-bed quantitative (177)Lu/(225)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 (213)Bi was imaged along with the peak at 208 keV (width: 15%) of (177)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 (225)Ac and (177)Lu, respectively. RESULTS: Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [(177)Lu]Lu-PSMA-I&T and [(225)Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [(225)Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [(177)Lu]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 [(225)Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [(177)Lu]Lu-PSMA-I&T/[(225)Ac]Ac-PSMA-I&T therapy indicates accumulation of free (213)Bi in the kidneys. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-022-06092-1.