FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer

Singh, N.; Need, E.; Berndt, A.; Goff, M.; Wilson, L.; Mourtada, F.; Guo, F.; Mastren, T.; Al-Hilal, T.; Sood, A. K.; Maity, A.; Miller, S. C.; Minoshima, S.; Goel, S.; Shi, S.

doi:10.1101/2025.10.27.684721

bioRxiv · 10.1101/2025.10.27.684721

FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer

Singh, N.·Need, E.·Berndt, A.·Goff, M.·Wilson, L.·Mourtada, F.·Guo, F.·Mastren, T.·Al-Hilal, T.·Sood, A. K.·Maity, A.·Miller, S. C.·Minoshima, S.·Goel, S.·Shi, S.

View original source ↗Export metadata ↓

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 (225Ac), 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 225Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal PET imaging demonstrated high tumor-specific uptake of FOLR1 in SKOV3 xenografts. FOLR1-targeted 225Ac 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 225Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer.

Source connections

Published article ↗

Explore related subjects

bioengineering Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Singh, N., Need, E., Berndt, A., Goff, M., Wilson, L., Mourtada, F., Guo, F., Mastren, T., Al-Hilal, T., Sood, A. K., Maity, A., Miller, S. C., Minoshima, S., Goel, S., Shi, S.. 2025-10-27. FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer. https://doi.org/10.1101/2025.10.27.684721

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Single-Component Photo-Crosslinked Lipoic Acid Functionalized Mucin Hydrogels: Dynamic Mucus Mimetics for Antiviral Protection

Native mucus protects epithelial surfaces through viscoelastic networks of disulfide-linked mucins. However, commercially available mucins often fail to reconstitute comparable mechanical and barrier properties, while synthetic and hybrid mucus mimetics require polymeric crosslinkers that may alter mucus-like composition. Inspired by the native architecture, we directly functionalized porcine gastric and bovine submaxillary mucins with -lipoic acid to develop a single-component, photo-crosslinkable hydrogels. Upon UV irradiation (365 nm), the modified mucins rapidly form disulfide-crosslinked networks without added photo-initiator/ polymeric crosslinkers, two orders of magnitude faster as compared with PEG-SH approaches. The resulting mucin-lipoic acid (MUC-LA) hydrogels exhibit mucus-relevant properties, including tunable viscoelasticity, redox responsiveness, self-healing, and size-dependent restrictions on nanoparticle transport. In transwell-based infection models, MUC-LA hydrogels (2-3%) mimicking the healthy airway mucus (G' {approx} 10-20 Pa) suppress epithelial infection by SARS-CoV-2 and influenza A virus. Crosslinked MUC-LA provides greater protection against SARS-CoV-2 than the non-crosslinked, whereas both formulations suppress influenza A infection, suggesting distinct contributions from network formation and mucin-associated interactions. These findings establish a dynamic, mucus-mimetic platform integrating rapid photo-gelation, controllable mechanics, selective transport, and antiviral barrier functionality. MUC-LA hydrogels offer opportunities to investigate mucosal transport and host-pathogen interactions, with potential applications in drug delivery, and as biomaterials.

bioengineering↗

bioRxiv2026

A Fibrous Optofluidic Probe for Endovascular Sensing of Blood Oxygenation and Flow Velocity

Local hemodynamic information including blood oxygenation and flow velocity could guide vascular interventions, yet obtaining these parameters in deep, narrow vessels remains challenging. Here, we report a flexible, submillimeter-scale fibrous optofluidic probe for endovascular sensing of blood oxygenation and flow velocity. The probe integrates a polymer optical fiber for light transmission with a microfluidic tube for dye injection, enabling spectroscopic oximetry and fluorescence dilution-based velocimetry through a single device. Via vascular intervention, we demonstrate local hemodynamic sensing in rabbit arteries and angiography-guided deployment in canine carotid arteries. The probe captures local changes in blood oxygenation and flow velocity during vascular occlusion and reperfusion, revealing hemodynamic disturbances that are not reflected in peripheral monitors. These results illustrate the complementary information provided by local oximetry and velocimetry and establish a compact optofluidic platform for quantitative hemodynamic monitoring during vascular interventions.

bioengineering↗

bioRxiv2026

Broad-spectrum in situ genetic reprogramming of native microbiomes

Complex microbial communities are found throughout terrestrial, aquatic, and animal-associated ecosystems. Genetic modification of discrete microbial taxa within native communities represents a powerful tool to study and augment microbiome functions. Herein, we develop Synthetic Phage Assisted Reprogrammable and Targetable Addition (SPARTA) as a one-step strategy for packaging, delivering, and integrating large synthetic DNA into a broad range of native microbiomes. SPARTA leverages a broad-spectrum synthetic phage particle for in situ genome engineering within complex soil, freshwater, and mammalian fecal microbiomes, reprogramming 59 native species across 16 families. By modulating SPARTA components, we further demonstrated tunability of SPARTA towards targeted microbiome population. Additionally, we built a novel companion tool to quantitatively identify engineered taxa, named 16S crRNA-guided inference of bacterial engineering sequencing or ScRibe-seq. The SPARTA-ScRibe-seq pipeline delivered and validated functional synthetic gene clusters in diverse native microbiomes while preserving the original microbial community structure. Together, this novel genome engineering framework constitutes an end-to-end programmable platform for rational and customizable reprogramming of native microbiomes.

bioengineering↗