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

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.