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Novel Radioimmunotherapy Eradicates Cancer Stem Cells in Ovarian Cancer Model

Reston, VA (July 24, 2025)—A new radioimmunotherapy approach has been shown to successfully eliminate cancer stem cells (CSCs) in preclinical models of ovarian cancer, outperforming the current gold standard. This research, published in the July issue of The Journal of Nuclear Medicine, lays the foundation for further development of radionuclide therapies targeting CSCs, offering renewed hope for more effective treatment options and improved outcomes for patients.

CSCs are highly tumorigenic, self-renewable cells that play a key role in tumor relapse, metastasis, and therapy resistance. Although the clinical significance of eliminating CSCs is clearly recognized and CSC immunotherapies have been examined in preclinical and clinical evaluations, the development of such therapies remains a challenge. 

“Radioimmunotherapy enables precise, target-specific delivery of particulate radiation to cancer-associated antigens, while minimizing off-target accumulation and increasing tumor retention and irradiation, which makes it a promising choice for targeting CSCs,” stated  Jürgen Grünberg, PhD, senior scientist at the Center for Radiopharmaceutical Sciences, Center for Life Sciences at the Paul Scherrer Institute in Villigen, Switzerland. “Our study sought to investigate the effectiveness of a new radionuclide Terbium-161 (¹⁶¹Tb ) for eradicating CSCs due to emission of short-ranged conversion and Auger electrons—besides beta-minus particle—successfully eliminated ovarian CSCs in contrast to Lutetium-177 (¹⁷⁷Lu).”

Researchers identified CSC-associated biomarkers (L1CAM⁺/CD133⁺) in an ovarian cancer sample and then created radiolabeled immunoconjugates with ¹⁷⁷Lu or ¹⁶¹Tb to target these CSCs. The cytotoxicity of the radioimmunoconjugates (¹⁷⁷Lu-DOTA-chCE7 and ¹⁶¹Tb-DOTA-chCE7) was measured by cell proliferation assays in vitro and in xenografted mouse models in vivo.

¹⁶¹Tb-DOTA-chCE7 showed significantly increased cytotoxicity, compared with ¹⁷⁷Lu-DOTA-chCE7, eliminating all ovarian CSCs and tumor cells differentiated from the CSCs in vivo.

“This signifies a pivotal step toward the translation of ¹⁶¹Tb-based therapies into clinical application,” noted Tihomir Todorov, PhD, junior scientist at the Center for Radiopharmaceutical Sciences, Center for Life Sciences at the Paul Scherrer Institute. “Targeted radionuclide therapies with ¹⁶¹Tb could support personalized medicine leading to advancements in cancer care including eradication of resistant CSCs and increased therapeutic efficacy alongside improved diagnosis, detection, and treatment monitoring.”

Graphical Abstract: Anti-L1CAM radioimmunotherapy with ¹⁶¹Tb shows the potential to kill ovarian cancer stem cells. Researchers confirmed the presence of L1CAM+/CD133+ ovarian cancer stem cells in patient samples for the first time. Anti-LCAM treatment with ¹⁶¹Tb resulted in higher cellular toxicity. Anti-L1CAM radioimmunotherapy with ¹⁶¹Tb successfully eliminated L1CAM+/CD133+ ovarian cancer stem cells in mouse models, which completely prevented tumor growth. These results signify a key proof of concept that ¹⁶¹Tb could successfully kill cancer stem cells, addressing this main clinical challenge in cancer care.

The authors of “¹⁶¹Tb-Based Anti-L1CAM Radioimmunotherapy Shows Superior Efficacy in Eliminating Ovarian Cancer Stem Cells Compared with ¹⁷⁷Lu in Preclinical Models of Ovarian Cancer” include Tihomir Zh. Todorov, PSI Center for Life Sciences, Villigen, Switzerland, Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland, and Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; Ricardo Coelho and Francis Jacob, Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland; Sharon Dellea, Pascal V. Grundler, Martin P. Béhé, and Jürgen Grünberg, PSI Center for Life Sciences, Villigen, Switzerland; Viola Heinzelmann-Schwarz, Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland and Department of Gynecology and Gynecological Oncology, Hospital for Women, University Hospital Basel, Basel, Switzerland; Nicholas P. van der Meulen, PSI Center for Life Sciences, Villigen, Switzerland and Laboratory of Radiochemistry, Paul Scherrer Institute, Villigen, Switzerland; and Roger Schibli, PSI Center for Life Sciences, Villigen, Switzerland and Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

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The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed 15 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

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