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Targeted alpha therapy (TAT) using 225Ac-PSMA ligands is a promising therapy option for advanced metastatic castration-resistant prostate cancer (mCRPC) [1]. The 225Ac decay chain shows a noticeable gamma emission (440 keV, 25.9%; 218 keV, 11.4%). However, recommended low therapeutic activities (4–8 MBq) limit the clinical applicability of SPECT [2], although initial attempts for 225Ac imaging exist [3, 4]. Particularly quantitative SPECT is a vital tool to assess dosimetry and therapy response. While the 218-keV-peak is characterized by a lower branching ratio and a higher scatter fraction, SPECT imaging of high-energy gammas such as 440 keV causes a complex detector point spread function (PSF) [5].
In this study, we would like to demonstrate the general feasibility of image-based dosimetry for 225Ac radionuclide therapy using quantitative 225Ac SPECT. For a mCRPC patient (65 years), imaging of the abdomen was performed 24 h p. i. of 8.1 MBq 225Ac-PSMA-I&T on a Siemens Symbia Intevo T16 SPECT/CT (440 keV (width, 20%), lower adjacent window (width, 10%), HEGP collimator, 16 projections/head, 128 × 128 pixel, 210 s/projection). Reconstruction was carried out via a MAP algorithm (30i1s) [6], including CT-based attenuation and dual-energy-window scatter correction and a simulated distance-dependent 2D PSF model (SIMIND). Final absorbed dose assessment was performed by combining the single 225Ac image with the effective half-life information determined from a previous 177Lu-PSMA-I&T imaging sequence [7]. This resulted in an absorbed dose of 0.18 and 0.17 SvRBE = 5/MBq for the left and right kidney, respectively, compared with 0.27 and 0.24 Gy/GBq for the preceding 177Lu cycle (6.2 GBq). A comparison with the pre-therapy 18F-PSMA-I&T PET/CT demonstrates that 225Ac SPECT imaging for this patient was able to locate a small lesion in the right hip. The 225Ac-absorbed dose was determined as 0.26 SvRBE = 5/MBq, compared with 0.35 Gy/GBq for 177Lu-PSMA-I&T.
Our analysis demonstrates the feasibility of dosimetry for 225Ac-PSMA-I&T, which provides further insights into theranostic approaches using TAT in mCRPC patients.
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All procedures performed in this study involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The retrospective evaluation was approved by the local ethic committee (20-178). Written informed consent was obtained prior to the exam.
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Gosewisch, A., Schleske, M., Gildehaus, F.J. et al. Image-based dosimetry for 225Ac-PSMA-I&T therapy using quantitative SPECT. Eur J Nucl Med Mol Imaging 48, 1260–1261 (2021). https://doi.org/10.1007/s00259-020-05024-1
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DOI: https://doi.org/10.1007/s00259-020-05024-1