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

Eur J Nucl Med Mol Imaging. 2023 Apr;50(5):1280-1290. doi: 10.1007/s00259-022-06092-1. Epub 2023 Jan 11.

Abstract

Purpose: Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225Ac-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 [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T treatment.

Methods: Eight prostate cancer patients (1000 MBq/8 MBq [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T) received a single-bed quantitative 177Lu/225Ac 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 213Bi was imaged along with the peak at 208 keV (width: 15%) of 177Lu. 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 225Ac and 177Lu, respectively.

Results: Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [177Lu]Lu-PSMA-I&T and [225Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [225Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [177Lu]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 [225Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213Bi in the kidneys.

Keywords: 225Ac; Dosimetry; PSMA; Prostate cancer; SPECT.

MeSH terms

  • Dipeptides / therapeutic use
  • Heterocyclic Compounds, 1-Ring / therapeutic use
  • Humans
  • Isotopes
  • Male
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant* / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / radiotherapy
  • Radiopharmaceuticals* / therapeutic use
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Dipeptides
  • Heterocyclic Compounds, 1-Ring
  • Isotopes
  • Prostate-Specific Antigen
  • Radiopharmaceuticals
  • Lutetium-177
  • Actinium-225