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

Neetu Singh1, Esther Need1, Ayden Berndt2

  • 1Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USA.

Science Advances
|June 24, 2026
PubMed

Insights

Targeted alpha particle therapy using actinium-225 (225Ac) shows promise for ovarian cancer. This novel approach demonstrated significant tumor regression and survival benefits with minimal toxicity in preclinical models.

Area of Science:

  • Oncology
  • Nuclear Medicine
  • Radiopharmaceutical Therapy

Background:

  • Ovarian cancer presents challenges due to poor prognosis, relapse, and acquired resistance to conventional therapies.
  • Targeted alpha particle therapy, especially using actinium-225 (225Ac), offers a promising new avenue for refractory cancers.

Purpose of the Study:

  • To evaluate the efficacy and safety of folate receptor 1 (FOLR1)-targeted 225Ac alpha-particle therapy for ovarian cancer treatment.

Main Methods:

  • Utilized an anti-FOLR1 antibody conjugated with 225Ac (αFOLR1) for targeted delivery.
  • Assessed tumor uptake via longitudinal positron emission tomography (PET) imaging in SKOV3 xenografts.
  • Evaluated therapeutic efficacy, survival rates, tumor elimination, DNA damage, and toxicity in preclinical models.
  • Performed human dosimetry estimations to assess safety.

Main Results:

  • αFOLR1 demonstrated high tumor-specific uptake in SKOV3 xenografts.
  • 225Ac therapy achieved significant tumor regression, 80% survival, and 40% complete tumor elimination.
  • Treatment induced tumor-specific double-stranded DNA damage without observable toxicity in normal tissues.
  • Human dosimetry estimates indicated high tumor absorbed dose and minimal absorbed dose to healthy tissues.

Conclusions:

  • FOLR1-targeted 225Ac alpha-particle therapy is an effective and safe treatment for ovarian cancer.
  • The therapy exhibits high feasibility for clinical translation in treating ovarian cancer, particularly refractory cases.

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