ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1563387
This article is part of the Research TopicTherapeutic Isotope Supply and Radiopharmaceutical Manufacturing for Cancer CareView all articles
Immunomodulatory Effects of Alpha vs Beta Radiopharmaceutical Therapy in Murine Prostate Cancer
Provisionally accepted
Carolina De Aguiar Ferreira1
Hemanth Potluri2
Mojdeh Mahmoudian1Christopher Massey2
Joseph Grudzinski2
Amanda Carston2
Nathan Clemons2
Malick BIO IDRISSOU2Anna Thickens2
Zachary Rosenkrans2
Cynthia Choi2Caroline Kerr2Anatoly Pinchuk2
Ohyun Kwon2Justin J Jeffery2
Bryan P Bednarz2
Zachary Scott Morris2Jamey Weichert2
Douglas G. McNeel2
Reinier Hernandez2*- 1Michigan State University, East Lansing, United States
- 2University of Wisconsin-Madison, Madison, Wisconsin, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Radiation therapy can modulate the tumor microenvironment (TME), influencing antitumor immune responses. This study compared the immunomodulatory effects of alpha-emitting ( 225 Ac) and beta-emitting ( 177 Lu) radiopharmaceutical therapies (RPT) using NM600 in murine prostate cancer models. Methods: We assessed immunological changes in TRAMP-C1 and Myc-CaP tumor models treated with 225 Ac-NM600 or 177 Lu-NM600. Flow cytometry was used to profile immune cell populations, activation markers, and checkpoint molecules, while multiplex assays analyzed cytokine and chemokine expression. Results: In general, 225 Ac-NM600 elicited stronger immunomodulatory effects than 177 Lu-NM600, including cell line dependent increased CD8/Treg ratios, activation of effector and memory T cells, and depletion of suppressive Tregs and MDSCs. The treatment elevated Th1 cytokines, pro-inflammatory chemokines, and checkpoint molecules like PD-1 on CD8+ T cells and PD-L1 on MDSCs, creating a more "hot" TME. Conclusion: Alpha-emitting 225 Ac-NM600 demonstrated superior ability to enhance antitumor immunity compared to beta-emitting 177 Lu-NM600. These findings support the use of 225 Ac-NM600 in combination with immunotherapies for advanced prostate cancer treatment.
Keywords: Immunomodulation, Tumor Microenvironment, targeted alpha therapy, prostate cancer, Radiopharmaceutical therapy, radionuclides
Received: 19 Jan 2025; Accepted: 23 Apr 2025.
Copyright: © 2025 De Aguiar Ferreira, Potluri, Mahmoudian, Massey, Grudzinski, Carston, Clemons, BIO IDRISSOU, Thickens, Rosenkrans, Choi, Kerr, Pinchuk, Kwon, Jeffery, Bednarz, Morris, Weichert, McNeel and Hernandez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Reinier Hernandez, University of Wisconsin-Madison, Madison, 53715-1149, Wisconsin, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.