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Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis.

Janina Baranowska-Kortylewicz¹, John G Sharp², Timothy R McGuire³

¹Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.

Cancer Biotherapy & Radiopharmaceuticals

|February 20, 2020

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This summary is machine-generated.

New targeted therapies using Thorium-227 (²²⁷Th) show promise for treating multifocal osteosarcoma (OST). These molecular probes can detect and treat resistant cancer cells with minimal side effects, offering a new theranostic approach.

Area of Science:

Oncology
Nuclear Medicine
Radiopharmaceutical Therapy

Background:

Osteosarcoma (OST) is a common bone cancer in children and adolescents, with poor prognosis for metastatic or relapsed cases.
Multifocal OST presents challenges due to chemotherapy-resistant tumor-initiating cells and the risks of aggressive treatments.
Current treatment limitations necessitate novel approaches for effectively managing multifocal and resistant osteosarcoma.

Purpose of the Study:

To evaluate the potential of ²²⁷Th-labeled molecular probes for detecting and treating multifocal osteosarcoma (OST).
To explore the theranostic application of ²²⁷Th in individualized OST treatment.
To assess the efficacy and safety profile of ²²⁷Th-based radiopharmaceutical therapy for OST.

Main Methods:

Keywords:

Thorium-227 multifocal osteosarcoma α-particle therapy

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Development of ²²⁷Th-labeled molecular probes targeting OST-associated receptors like IGF-1R, HER2, and PSMA.

Investigating the properties of ²²⁷Th, including its limited myelotoxicity and stable chelation.

Analyzing the decay properties of ²²⁷Th and its daughter ²²³Ra for targeted alpha therapy and imaging.

Main Results:

²²⁷Th probes are expected to detect and treat both osseous and non-osseous sites of multifocal OST.
²²⁷Th and its daughter ²²³Ra incorporate into bone lesions, delivering targeted alpha radiation.
Alpha particles from ²²⁷Th and ²²³Ra exhibit high relative biological effectiveness, effective against resistant and quiescent OST cells.
Quantitative SPECT imaging of ²²⁷Th and ²²³Ra is feasible, supporting theranostic applications.

Conclusions:

²²⁷Th-based molecular probes offer a promising theranostic strategy for multifocal osteosarcoma (OST).
Targeted alpha therapy with ²²⁷Th demonstrates potential for overcoming chemotherapy resistance in OST.
The combination of imaging and therapy with ²²⁷Th supports individualized treatment of OST patients.