# Antibody-based prertargeted alpha particle therapy for ovarian cancer

> **NIH NIH R42** · VIEWPOINT MOLECULAR TARGETING, INC. · 2024 · $391,553

## Abstract

Project Summary
High-grade serous ovarian carcinomas (HGSOC) account for 75% of ovarian cancer diagnoses, and about 80%
of patients have metastatic disease upon diagnosis. Metastatic HGSOC is typically treated by radical surgical
debulking and cytotoxic chemotherapy, but ~80% of patients’ disease will recur within 3 years, leading to a
median overall survival of only 40 months. Targeted therapies have demonstrated only marginal improvements
in outcomes for HGSOC, and new therapeutic approaches are urgently needed. Image-guided targeted alpha-
particle therapy (alpha-TRT) has emerged as an effective intervention for several cancers, and the
commercialization of an alpha-TRT for metastatic HGSOC is significant because success in our efforts will
improve outcomes for the thousands of patients that do not benefit from or relapse after frontline therapies.
The overall goal of this proposal is to commercialize a new alpha-TRT that can improve outcomes for the
thousands of metastatic HGSOC patients for whom all other therapies fall short. To achieve this goal we will
combine Perspective Therapeutics’ proprietary radionuclide chelation and 212Pb isotope production
technologies with an innovative cucurbit[7]uril-adamantane (CB7-Adma) “host:guest pretargeting” platform to
deliver an image-guided alpha-TRT therapeutic using elementally-matched radionuclides 203Pb (imaging) and
212Pb (therapy). This therapeutic approach will target tumor associated glycoprotein 72 (TAG72), a well-
established biomarker that is overexpressed in the majority of HGSOC tumors.
In Phase 1 of this Fast Track STTR project, we will demonstrate the feasibility of the pretargeting approach to
alpha-TRT using a humanized TAG72 monoclonal antibody (huCC49) in mouse models of HGSOC,
demonstrating that the dosimetry-derived therapeutic index meets recognized benchmarks for effective TRT.
Additionally, we will validate huCC49 for this indication by performing immunohistochemistry (IHC) on human
HGSOC samples. In Phase 2, we will optimize our pretargeted alpha-TRT in mice, determining the dose-
dependent tumor growth inhibition, survival, and potential toxicities of the approach. Simultaneously, we will
optimize 212Pb radioligand synthesis and formulation to establish the optimal formulation (and shelf life) for
distribution to clinical sites and CMC preparation. Furthermore, we will synthesize, purify, and characterize
sufficient material to perform GLP toxicology of the “cold” small molecule radioligand according to FDA guidance.
In sum, we will have optimized a protocol for producing and delivering image-guided dosimetry-based
pretargeted alpha-TRT in mice that forms a rigorous basis for human HGSOC therapy. Thus, with success in
our STTR project Aims, Perspective will be prepared for FDA filings (CMC/IND) to support a Phase I clinical trial
that will be financed using private capital as the company has done for previous programs.

## Key facts

- **NIH application ID:** 10821914
- **Project number:** 1R42CA287696-01
- **Recipient organization:** VIEWPOINT MOLECULAR TARGETING, INC.
- **Principal Investigator:** Jacob Houghton
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,553
- **Award type:** 1
- **Project period:** 2024-06-05 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821914

## Citation

> US National Institutes of Health, RePORTER application 10821914, Antibody-based prertargeted alpha particle therapy for ovarian cancer (1R42CA287696-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10821914. Licensed CC0.

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