# A Scoping Review of the Challenges and Future Perspectives in the Use of Alpha-Emitters for Metastatic Ovarian Cancer

## TL;DR

This review explores the potential and challenges of using alpha-particle therapy to treat advanced ovarian cancer, focusing on its ability to target small tumor clusters and improve survival.

## Contribution

The paper provides a comprehensive scoping review of pre-clinical and clinical studies on alpha-emitters for metastatic ovarian cancer, highlighting key challenges and future directions.

## Key findings

- Alpha-particle therapy shows promise in targeting microscopic residual tumors in the peritoneal cavity.
- Challenges include heterogeneous antigen expression, off-target toxicity, and radionuclide availability.
- Early treatment outcomes indicate efficacy but highlight the need for improved clinical trial design and dosimetry.

## Abstract

Ovarian cancer (OC) is frequently diagnosed at an advanced stage and characterized by high rates of recurrence despite aggressive cytoreductive surgery and chemotherapy. Relapse is driven by microscopic residual tumors that are disseminated most often throughout the peritoneal cavity, posing significant challenges with conventional systemic therapy. Targeted alpha-particle therapy (TAT) combines molecular targeting with alpha-emitting radionuclides to deliver highly potent and localized cellular damage, uniquely suited for the eradication of small OC tumor clusters within the peritoneal cavity. We conducted an extensive literature search for clinical trials (clinicaltrials.gov) and pre-clinical studies (PubMed, Scopus, Google Scholar) between September 2025 and November 2025. Peer-reviewed articles published in English over the past 20 years that used OC mouse models with reported treatment data were included. Review articles without original data and clinical trials that have been terminated or withdrawn were excluded. In this review, we (1) summarize the biological and physical rationale supporting the use of TAT in OC, (2) discuss the relevant molecular and immunological anti-tumor mechanisms, and (3) critically evaluate early treatment outcomes of 19 pre-clinical and four clinical studies with respect to efficacy, safety, and feasibility. Despite the progress and promising survival outcomes, several challenges remain, including heterogeneous antigen expression, delivery and retention within the peritoneal cavity, off-target toxicity, radiation resistance, radionuclide availability, dosimetry uncertainties, and limitations in clinical trial design. We highlight future directions to overcome these barriers and the continued multidisciplinary efforts essential to translate TAT into effective clinical strategies to treat advanced stages of OC and other solid tumors resistant to conventional treatment. This work was supported with funding available to Kurt R. Zinn as the Hickman Family Endowed Chair in Oncology at Michigan State University.