Image-based dosimetry for 225Ac-PSMA-I&T therapy using quantitative SPECT

Kratochwil C, et al. Targeted alpha therapy of mCRPC with 225actinium-PSMA-617: dosimetry estimate and empirical dose finding. J Nucl Med. 2017;8(10):1624–31 p. jnumed. 117.191395. Article Google Scholar Robertson A, et al. Multi-isotope SPECT imaging of the 225Ac decay chain: feasibility studies. Phys Med Biol. 2017;62(11):4406. CAS Article Google Scholar Usmani S, et al. 225Ac prostate-specific membrane antigen posttherapy α imaging: comparing 2 and 3 photopeaks. Clin Nucl Med. 2019;44(5):401–3. Article Google Scholar Vatsa R, et al. 225Ac-PSMA-617 radioligand posttherapy imaging in metastatic castrate-resistant prostate cancer patient using 3 Photopeaks. Clin Nucl Med. 2020;45(6):437–8. Article Google Scholar Chun SY, Fessler JA, Dewaraja YK. Correction for collimator-detector response in SPECT using point spread function template. IEEE Trans Med Imaging. 2012;32(2):295–305. Article Google Scholar Delker A, et al. Dosimetry for 177 Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43(1):42–51. CAS Article Google Scholar Gosewisch A, et al. Patient-specific image-based bone marrow dosimetry in Lu-177-[DOTA 0, Tyr 3]-Octreotate and Lu-177-DKFZ-PSMA-617 therapy: investigation of a new hybrid image approach. EJNMMI Res. 2018;8(1):76. Article Google Scholar Download references Open Access funding enabled and organized by Projekt DEAL. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany A. Gosewisch, M. Schleske, F. J. Gildehaus, I. Berg, L. Kaiser, J. Brosch, P. Bartenstein, A. Todica, H. Ilhan & G. Boning You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to H. Ilhan. 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. The authors declare that they have no conflict of interest. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is part of the Topical Collection on Image of the month. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Reprints and Permissions 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 (2020). https://doi.org/10.1007/s00259-020-05024-1 Download citation Received: 13 June 2020 Accepted: 31 August 2020 Published: 21 September 2020 DOI: https://doi.org/10.1007/s00259-020-05024-1

The 225 Ac 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 225 Ac 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 225 Ac radionuclide therapy using quantitative 225 Ac SPECT. For a mCRPC patient (65 years), imaging of the abdomen was performed 24 h p. i. of 8.1 MBq 225 Ac-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 225 Ac image with the effective half-life information determined from a previous 177 Lu-PSMA-I&T imaging sequence [7]. This resulted in an absorbed dose of 0.18 and 0.17 Sv RBE = 5 /MBq for the left and right kidney, respectively, compared with 0.27 and 0.24 Gy/GBq for the preceding 177 Lu cycle (6.2 GBq). A comparison with the pre-therapy 18 F-PSMA-I&T PET/CT demonstrates that 225 Ac SPECT imaging for this patient was able to locate a small lesion in the right hip. The 225 Ac-absorbed dose was determined as 0.26 Sv RBE = 5 /MBq, compared with 0.35 Gy/GBq for 177 Lu-PSMA-I&T.
Our analysis demonstrates the feasibility of dosimetry for 225 Ac-PSMA-I&T, which provides further insights into theranostic approaches using TAT in mCRPC patients.
This article is part of the Topical Collection on Image of the month.
Funding Open Access funding enabled and organized by Projekt DEAL.

Compliance with ethical standards
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.

Conflict of interest
The authors declare that they have no conflict of interest.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.