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Updated: Jul 8, 2025
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of
Ioanna Liatsou1, Yingli Fu2, Zhi Li2
1Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ioanna.liatsou@gmail.com.
Purpose:
Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS.
Methods:
The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines.
Results:
Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively.
Conclusion:
This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.
Insights
Targeted alpha-particle therapy using actinium-225 labeled hu3F8 antibody shows promise for osteosarcoma (OS). This novel treatment demonstrated significant antitumor activity and improved survival in preclinical models, offering a new therapeutic avenue for OS patients.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Immunotherapy
Background:
- Osteosarcoma (OS) presents a poor prognosis, especially with metastasis and recurrence, necessitating novel therapeutic strategies.
- Targeted alpha-particle therapy offers a precise method to deliver cytotoxic radiation to tumor cells using tumor-specific antibodies.
- The hu3F8 antibody, an FDA-approved humanized anti-GD2 antibody, has shown potential for OS imaging and is being advanced for therapy.
Purpose of the Study:
- To evaluate the safety and therapeutic efficacy of the radiolabeled antibody [225Ac]Ac-DOTA-hu3F8 for osteosarcoma treatment.
- To advance the hu3F8 antibody system for targeted alpha-particle therapy in OS.
Main Methods:
- Radiolabeling of the hu3F8 antibody with actinium-225.
- Evaluation of [225Ac]Ac-DOTA-hu3F8 in orthotopic murine xenografts of OS.
- Assessment of therapeutic efficacy in spontaneously occurring OS in canines.
Main Results:
- Significant antitumor activity and delayed tumor growth (16-18 days) observed in murine models via bioluminescence and MRI.
- Delayed metastatic progression and extended survival in canine patients (211 and 437 days).
- Identified transient, radiation-induced renal toxicity with evidence of renal function recovery.
Conclusions:
- hu3F8-based alpha-particle therapy demonstrates significant potential as a promising treatment strategy for osteosarcoma.
- The findings support further clinical investigation of this targeted radiotherapeutic approach for OS.
