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Updated: Jan 10, 2026
Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer
Abstract:
Despite the advancement in therapies, ovarian cancer treatment is challenging due to poor prognosis and high relapse associated with acquired resistance. Targeting overexpression of FOLR1 in ovarian cancers has proven to be an attractive strategy. The recent FDA approval of FOLR1 targeted antibody drug conjugate has shown promising results albeit resistance with repeated use appears inevitable. Emerging targeted alpha-particle therapies, particularly Actinium-225 ( 225 Ac), for treating refractory cancers have opened avenues for improved therapeutic options. The success of alpha-particle therapy relies on tumor specific delivery of the alpha emitters. Herein we describe the first example of FOLR1-targeted 225 Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal PET imaging demonstrated high tumor-specific uptake of αFOLR1 in SKOV3 xenografts. FOLR1-targeted 225 Ac demonstrated high therapeutic efficacy achieving marked tumor regression, 80% survival and 40% complete response. The therapy resulted in tumor specific 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 225 Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer.
Insights
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.
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.
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