Biology subjects

Need, E.

Publications and source records attributed to Need, E..

3 recordsLinked to original sources

bioRxiv2025

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

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.

bioengineering↗

bioRxiv2024

Imaging-Guided Metabolic Radiosensitization of Pediatric Rhabdoid Tumors

Tumor hypoxia leads to radioresistance and markedly worse clinical outcomes for pediatric malignant rhabdoid tumors (MRT). Our transcriptomics and bioenergetic profiling data reveal that mitochondrial oxidative phosphorylation (OXPHOS) is a metabolic vulnerability of MRT and can be exploited to overcome consumptive hypoxia by repurposing an FDA-approved anti-malarial drug, Atovaquone (AVO). We then establish the utility of Oxygen-Enhanced-Multispectral Optoacoustic Tomography (OE-MSOT), a label-free, ionizing radiation-free imaging modality, to visualize and quantify spatiotemporal changes in tumor hypoxia in response to AVO. We show a potent but transient increase in tumor oxygenation upon AVO treatment which results in complete elimination of tumors in all tested mice when combined with 10 Gy radiotherapy, a dose several times lower than the current clinic standard. Finally, we use translational mathematical modeling for systematic evaluation of dosing regimens, administration timing, and therapeutic synergy in a virtual clinical patient population. Together, our work establishes a framework for safe and pediatric patient-friendly image-guided metabolic radiosensitization of rhabdoid tumors.

bioengineering↗

bioRxiv2024

Temporal interference electrical neurostimulation yields fMRI BOLD activation in humans

Temporal interference electrical neurostimulation (TI) is a relatively new method of non-invasive neurostimulation that may be able to stimulate deep brain regions without stimulating the overlying superficial regions. Despite studies in rodents, almost no studies have investigated its effects on human brain activity along with safety and tolerability profiles. We performed simultaneous TI stimulation and fMRI to investigate the effects of TI on human BOLD signals. Here we show that TI can induce increased BOLD activation in humans, with good safety and tolerability profiles. We also show the limits of spatial precision and explore the nature and causes of additional off target effects. TI may be a promising approach for addressing questions about the causal role of deep brain structures in human cognition and may also afford new clinical treatments.

neuroscience↗