Abstract
External beam radiotherapy plays a critical role in the treatment of most pediatric solid tumors. Particularly in children, achieving an optimal therapeutic index to avoid damage to normal tissue is extremely important. Consequently, in metastatic disease, the utility of external beam radiotherapy is very limited. Molecular radiotherapy with tumor-targeted radionuclides may overcome some of these challenges, but to date no single cancer selective agent exists, capable of treating various pediatric malignancies independent of their histopathological origin. We tested the therapeutic potential of the clinical-grade alkyl-phospholipid ether analog CLR1404 as scaffold for tumor-targeted radiotherapy of pediatric malignancies. Methods: Uptake of CLR1404 by pediatric solid tumor cells was tested in vitro, by flow cytometry, and in vivo, by positron emission tomography (PET)/computed tomography (CT) imaging and dosimetry. The therapeutic potential of 131I-CLR1404 was evaluated in xenograft models. Results: In vitro, fluorescent CLR1404-BODIPY showed significant selective uptake in a variety of pediatric cancer lines compared to normal controls. In vivo tumor-targeted uptake in mouse xenograft models using 124I-CLR1404 was confirmed by imaging. Single-dose intravenous injection of 131I-CLR1404 significantly delayed tumor growth in all rodent pediatric xenograft models and extended animal survival, while demonstrating a favorable side effect profile. Conclusion: 131I-CLR1404 has the potential to become a tumor-targeted radiotherapeutic drug with broad applicability in pediatric oncology. Since 131I-CLR1404 has entered clinical trials in adults, our data warrants the development of pediatric clinical trials for this particularly vulnerable patient population.
- Oncology: General
- Pediatrics
- Radionuclide Therapy
- microPET/CT imaging
- pediatric cancer
- radionuclide therapy
- targeted radiotherapy
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.