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Related Experiment Video

Updated: Jan 10, 2026

Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
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FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer.

Neetu Singh, Esther Need, Ayden Berndt

    Biorxiv : the Preprint Server for Biology
    |November 24, 2025
    PubMed
    Summary

    Targeting folate receptor alpha (FOLR1) with Actinium-225 (225Ac) alpha-particle therapy shows promise for ovarian cancer. This novel approach achieved significant tumor regression and survival benefits with minimal toxicity in preclinical models.

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    Area of Science:

    • Oncology
    • Nuclear Medicine
    • Radiopharmaceutical Therapy

    Background:

    • Ovarian cancer treatment faces challenges due to poor prognosis and acquired resistance.
    • Targeting folate receptor alpha (FOLR1), which is overexpressed in ovarian cancers, is a promising therapeutic strategy.
    • While antibody-drug conjugates targeting FOLR1 show promise, resistance is a concern, necessitating novel approaches like targeted alpha-particle therapy.

    Purpose of the Study:

    • To evaluate the efficacy and safety of FOLR1-targeted Actinium-225 (225Ac) alpha-particle therapy for ovarian cancer.
    • To assess tumor-specific delivery and therapeutic outcomes in a preclinical ovarian cancer model.

    Main Methods:

    • Development and characterization of a FOLR1-targeted 225Ac conjugate (αFOLR1).
    • Evaluation of tumor uptake using longitudinal PET imaging in SKOV3 xenografts.
    • Assessment of therapeutic efficacy, survival rates, and toxicity in preclinical models.
    • Analysis of DNA damage and human dosimetry estimations.

    Main Results:

    • αFOLR1 demonstrated high tumor-specific uptake in SKOV3 xenografts.
    • FOLR1-targeted 225Ac therapy achieved significant tumor regression, 80% survival, and 40% complete response.
    • The therapy induced tumor-specific double-stranded DNA damage.
    • Preclinical studies showed no obvious toxicity in normal tissues, and human dosimetry indicated a high tumor absorbed dose with minimal absorbed dose to healthy tissues.

    Conclusions:

    • FOLR1-targeted 225Ac alpha-particle therapy is an efficacious and safe treatment for ovarian cancer.
    • The therapy demonstrates high feasibility for clinical translation.
    • This approach offers a promising new avenue for managing refractory ovarian cancers.