# Alpha-Emitter Therapy of Osteosarcoma

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $681,116

## Abstract

ALPHA- EMITTER THERAPY OF OSTEOSARCOMA
PROJECT SUMMARY
Three-year overall survival for patients with recurrent osteosarcoma (OS) is 20%. Current therapy for metastatic
osteosarcoma (OS) is largely ineffective. Over the past four decades no new therapies have been identified for
OS. Our overall objective is to evaluate the potential efficacy and toxicity of targeted alpha-particle
radiopharmaceutical therapy (αRPT) against OS. Targeted alpha-emitter therapy is a promising treatment
modality that is not susceptible to the resistance mechanism observed for chemotherapy, traditional
radiotherapy, targeted (i.e., pathway inhibition) therapy and immunotherapy. This is because alpha-particles
cause massive and irreparable DNA double-strand break damage, irrespective of oxygenation, dose-rate, cell
signaling or mutational burden. Osteosarcoma expresses the ganglioside GD2 receptor that can be targeted by
the anti-GD2 antibody (Ab), Hu3F8. We propose to evaluate the safety and efficacy of 225Ac-Hu3F8 (A3F8) in a
naturally occurring, large animal model of osteosarcoma. Actinium-225 emits 4 alpha-particles per decay and
has a 10-day half-life. These experiments in client-owned dogs, which develop metastatic OS disease at a higher
rate than people, would be the first evaluation of radiopharmaceutical therapy (RPT) with an alpha-emitter-
conjugated Ab that targets both soft-tissue and calcified disseminated OS — a highly radioresistant disease.
A two-cycle treatment scheme will be used wherein a fixed administered activity (AA) of A3F8, will be directly
imaged by SPECT using a novel proprietary technique developed by Rapid, LLC (a Hopkins startup that has
licensed α-particle emitter dosimetry and imaging technology) to obtain pharmacokinetics (PK) for dosimetry and
treatment planning to identify the AA that balances potential toxicity with maximum anti-tumor efficacy. The
specific aims are: 1. Identify the maximum tolerated absorbed dose (MTAD) to the red marrow in client-owned
dogs with OS; utilizing SPECT imaging, collect PK to relate dose-limiting organ (DLO) absorbed dose (AD) to
measured toxicity. 2. Determine treatment efficacy at the MTAD. 3. Evaluate how different measured or
calculated quantities (e.g., tumor burden, tumor AD and DLO AD) are related to toxicity and efficacy. 4. Using
data collected in Aims 1-3, develop a pharmacokinetic/dosimetry model that will help guide optimization of αRPT
treatment in human OS patients. New treatments that are fundamentally different from those currently available
are urgently needed for osteosarcoma. Radiopharmaceutical therapy with the highly potent alpha-emitter, 225Ac,
is such a therapy. The proposed studies would yield required data to launch a clinical αRPT trial against OS in
humans.

## Key facts

- **NIH application ID:** 10978821
- **Project number:** 1R01CA285588-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DARA L KRAITCHMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $681,116
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978821

## Citation

> US National Institutes of Health, RePORTER application 10978821, Alpha-Emitter Therapy of Osteosarcoma (1R01CA285588-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10978821. Licensed CC0.

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