Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2023 Nov 28;24(23):16845.
doi: 10.3390/ijms242316845.

Comparative Analysis of Morphological and Functional Effects of 225Ac- and 177Lu-PSMA Radioligand Therapies (RLTs) on Salivary Glands

Benedikt Feuerecker  1   2   3   4 , Andrei Gafita  5 , Thomas Langbein  1 , Robert Tauber  6 , Christof Seidl  1 , Frank Bruchertseifer  7 , Jürgen E Gschwendt  6 , Wolfgang A Weber  1   2 , Calogero D'Alessandria  1 , Alfred Morgenstern  7 , Matthias Eiber  1   2
Affiliations
Comparative Study

Comparative Analysis of Morphological and Functional Effects of 225Ac- and 177Lu-PSMA Radioligand Therapies (RLTs) on Salivary Glands

Benedikt Feuerecker et al. Int J Mol Sci. .

Abstract

Most Prostate Specific Membrane Antigens (PSMAs) targeting small molecules accumulate in the salivary glands (SGs), raising concerns about SG toxicity, especially after repeated therapies or therapy with 225Ac-labeled ligands. SG toxicity is assessed clinically by the severity of patient-reported xerostomia, but this parameter can be challenging to objectively quantify. Therefore, we explored the feasibility of using SG volume as a biomarker for toxicity. In 21 patients with late-stage metastatic resistant prostate cancer (mCRPC), the PSMA volume and ligand uptake of SG were analyzed retrospectively before and after two cycles of 177Lu-PSMA (LuPSMA; cohort A) and before and after one cycle of 225Ac-PSMA-617 (AcPSMA, cohort B). Mean Volume-SG in cohort A was 59 ± 13 vs. 54 ± 16 mL (-10%, p = 0.4), and in cohort B, it was 50 ± 13 vs. 40 ± 11 mL (-20%, p = 0.007), respectively. A statistically significant decrease in the activity concentration in the SG was only observed in group B (SUVmean: 9.2 ± 2.8 vs. 5.3 ± 1.8, p < 0.0001; vs. A: SUVmean: 11.2 ± 3.3 vs. 11.1 ± 3.5, p = 0.8). SG volume and PSMA-ligand uptake are promising markers to monitor the SG toxicity after a PSMA RLT.

Keywords: Actinium-225-PSMA-617; PSMA; mCRPC; radioligand therapy; salivary glands; tumor sink effect; xerostomia.

PubMed Disclaimer

Conflict of interest statement

ME reports fees from Blue Earth Diagnostics Ltd. (consultant, research funding), Novartis/AAA (consultant, speaker), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Eckert-Ziegler (speaker), Janssen Pharmaceuticals (consultant, speakers bureau), Parexel (image review), and Bioclinica (image review) outside the submitted work and a patent application for rhPSMA. BF reports fees from Novartis (consultant). WW reports that he is on advisory boards and receives compensation from Bayer, Blue Earth Diagnostics, Endocyte, Reflexion, Rayzebio, Vida Ventures, ITM, and Pentixapharm. He has received research support from Siemens, BMS, Ipsen, Imaginab, and Piramal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.

Figures

Figure 1
Figure 1
Morphological changes in SG volume based on CT/MRI quantification after 177Lu-PSMA (A) and 225Ac-PSMA-617 (B).
Figure 2
Figure 2
Changes in SUVmax (the total of submandibular and parotid glands) after 177Lu-PSMA RLT (A) and after 225Ac-PSMA-617 RLT (B), respectively, and change in SUVmean (the total of submandibular and parotid glands) after 177Lu-PSMA RLT (C) and 225Ac-PSMA-617 RLT (D), respectively.
Figure 3
Figure 3
Changes in PSMA-SGU after 177Lu-177-PSMA RLT (A) and after 225Ac-PSMA-617 RLT (B), respectively.
Figure 4
Figure 4
SUVmax of the SG stratified by tumor burden before (pre) and after (post) 225Ac-PSMA-617 RLT and also stratified by tumor load (colors indicate groups). Group moderate, n = 3, all other groups, n = 4.
Figure 5
Figure 5
CT based segmentation (left) of submandibular (upper row) and parotid glands (lower row), and the illustration of its transfer to the respective PET images (right). Green colored areas indicate the respective salivary glands.
See this image and copyright information in PMC

References

    1. Sartor O., de Bono J., Chi K.N., Fizazi K., Herrmann K., Rahbar K., Tagawa S.T., Nordquist L.T., Vaishampayan N., El-Haddad G., et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2021;385:1091–1103. doi: 10.1056/NEJMoa2107322. - DOI - PMC - PubMed
    1. Rahbar K., Ahmadzadehfar H., Kratochwil C., Haberkorn U., Schafers M., Essler M., Baum R.P., Kulkarni H.R., Schmidt M., Drzezga A., et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J. Nucl. Med. 2017;58:85–90. doi: 10.2967/jnumed.116.183194. - DOI - PubMed
    1. Kratochwil C., Bruchertseifer F., Rathke H., Hohenfellner M., Giesel F.L., Haberkorn U., Morgenstern A. Targeted alpha-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control. J. Nucl. Med. 2018;59:795–802. doi: 10.2967/jnumed.117.203539. - DOI - PubMed
    1. Kratochwil C., Bruchertseifer F., Giesel F.L., Weis M., Verburg F.A., Mottaghy F., Kopka K., Apostolidis C., Haberkorn U., Morgenstern A. 225Ac-PSMA-617 for PSMA-Targeted alpha-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. J. Nucl. Med. 2016;57:1941–1944. doi: 10.2967/jnumed.116.178673. - DOI - PubMed
    1. Zacherl M.J., Gildehaus F.J., Mittlmeier L., Boning G., Gosewisch A., Wenter V., Unterrainer M., Schmidt-Hegemann N., Belka C., Kretschmer A., et al. First Clinical Results for PSMA-Targeted alpha-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. J. Nucl. Med. 2021;62:669–674. - PubMed

Publication types