FOLR1-targeted actinium-225 alpha-particle therapy eliminates ovarian cancer

Q: Why is ovarian cancer challenging to treat with current therapies?

Ovarian cancer often presents at advanced stages with poor prognosis and limited options. Many patients relapse within two years, and recurrent tumors frequently resist taxane and platinum treatments.

Q: What is the main therapeutic strategy described in the document?

The document presents FOLR1-targeted actinium-225 (225Ac) alpha-particle therapy for ovarian cancer. It aims to deliver alpha radiation specifically to FOLR1-expressing tumor cells.

Q: What efficacy and safety outcomes are reported for the FOLR1-targeted 225Ac therapy?

FOLR1-targeted 225Ac achieved marked tumor regression, 80% survival, and 40% complete tumor elimination. The study reports tumorspecific DNA damage with no obvious toxicity in normal tissues and dosimetry indicating minimal absorbed dose in healthy tissues.

Sep 22, 2026

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Ovarian cancer remains difficult to treat due to poor prognosis, relapse, and therapy resistance. This study describes a folate receptor 1 (FOLR1)-targeted actinium-225 (225Ac) alpha-particle therapy for ovarian cancer. Longitudinal positron emission tomography showed high tumor-specific αFOLR1 uptake in SKOV3 xenografts, while treatment produced marked tumor regression, 80% survival, and 40% complete elimination. Tumors exhibited double-stranded DNA damage with no obvious toxicity, and dosimetry indicated high tumor dose with minimal exposure to healthy tissues, supporting clinical feasibility.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Targeted alpha-particle therapy and actinium-225 rationale

FOLR1 as a molecular target in ovarian cancer

Prior FOLR1-targeted therapies and unmet need

CANCER FOLR1-targeted actinium-225–based alpha-particle therapy eliminates ovarian cancer Neetu Singh1, Esther Need1, Ayden Berndt2, Matthew Goff1, Lydia J. Wilson3, Firas Mourtada3, Feng Guo4, Tara Mastren5, Taslim Al-Hilal1,2, Anil K. Sood6, Amit Maity7, Scott C. Miller8, Satoshi Minoshima8, Shreya Goel1,2,8*, Sixiang Shi1,8* Despite the advancement in therapies, ovarian cancer treatment is challenging because of poor prognosis and high relapse associated with acquired resistance. Emerging targeted alpha particles, particularly actinium-225 (225Ac), for treating refractory cancers have opened avenues for improved therapeutic options. Here, we describe a successful example of folate receptor 1 (FOLR1)–targeted 225Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal positron emission tomography imaging demonstrated high tumor-specific uptake of αFOLR1 (anti-FOLR1 antibody) in SKOV3 xenografts. FOLR1-targeted 225Ac demonstrated high therapeutic efficacy, achieving marked tumor regression, 80% survival, and 40% complete tumor elimination. The therapy resulted in tumorspecific double-stranded DNA damage, and no obvious toxicity was observed in normal tissues. Estimated human dosimetry showed high absorbed dose for tumor and minimal absorbed dose for healthy tissues, establishing its safety. In totality, FOLR1-targeted 225Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer. copyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY-nc) . INTRODUCTION Ovarian cancer is the fifth leading cause of cancer-associated death among women and often presented at advanced stages with poor prognosis and limited therapeutic treatment options (1, 2) . Patients with ovarian cancer experience high morbidity and mortality with median survival rates of 40 to 50% at stage III and only ~ 17% at stage IV (3, 4). Despite the advances in surgical interventions and well-designed treatment regimens with chemotherapy agents, most patients relapse within 2 years, and many recurrent tumors are taxane and platinum resistant (4, 5). Intrinsic or acquired resistance to therapies limits their benefit in advanced ovarian cancers, highlighting the critical unmet need to explore alternative therapeutic directions (6–8). Targeted alpha-particle therapy (TAT) has emerged as a promising approach with demonstrable clinical success, especially for the cancer types that cannot be completely removed by surgical resection and are resistant to frontline chemo-and immunotherapies (6, 9–11) . Compared with beta emitters (which primarily induce single-stranded DNA breaks in target cells), the alpha emitter actinium-225 (225Ac) has higher linear energy transfer (11, 12) . This results in more lethal double-stranded DNA breaks that are difficult to repair and can effectively kill tumor cells. As such, TAT remains effective despite conventional cellular resistance mechanisms (13, 14) . In addition, 225Ac has a short path length (<100 μm) in tissues, which confines its impact to neighboring cells and substantially reduces offtarget toxicity ( 15–17) . Therefore, 225Ac-based TAT is a promising 1department of Molecular Pharmaceutics, University of Utah, Salt lake city, Ut 84112, USA. 2department of Biomedical engineering, University of Utah, Salt lake city, Ut 84112, USA. 3department of Radiation Oncology, thomas Jefferson University, Philadelphia, PA 19107, USA. 4department of Pancreatic Surgery, Union hospital, tongji Medical college, huazhong University of Science and technology, Wuhan 430022, china. 5department of civil and environmental engineering, University of Utah, Salt lake city, Ut 84112, USA. 6department of Gynecologic Oncology and Reproductive Medicine, th

FAQs

Why is ovarian cancer challenging to treat with current therapies?

Ovarian cancer often presents at advanced stages with poor prognosis and limited options. Many patients relapse within two years, and recurrent tumors frequently resist taxane and platinum treatments.

What is the main therapeutic strategy described in the document?

The document presents FOLR1-targeted actinium-225 (225Ac) alpha-particle therapy for ovarian cancer. It aims to deliver alpha radiation specifically to FOLR1-expressing tumor cells.

What efficacy and safety outcomes are reported for the FOLR1-targeted 225Ac therapy?

FOLR1-targeted 225Ac achieved marked tumor regression, 80% survival, and 40% complete tumor elimination. The study reports tumorspecific DNA damage with no obvious toxicity in normal tissues and dosimetry indicating minimal absorbed dose in healthy tissues.

Sep 22, 2026

Upload by Jasmine