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 limited. Molecular radiotherapy with tumor-targeted radionuclides may 
overcome some of these challenges, but to date there exists no single 
cancer-selective agent capable of treating various pediatric malignancies 
independently of their histopathologic origin. We tested the therapeutic 
potential of the clinical-grade alkyl-phospholipid ether analog CLR1404, 
18-(p-iodophenyl)octadecyl phosphocholine, as a 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 PET/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 
with 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. Because 131I-CLR1404 has entered clinical trials in adults, our data 
warrant the development of pediatric clinical trials for this particularly 
vulnerable patient population.