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.

外部束放射疗法在大多数儿童实体瘤的治疗中起着至关重要的作用。特别是对于儿童，获得最佳治疗指标以避免对正常组织的损害极为重要。因此，在转移性疾病中，束外放射疗法的应用受到限制。靶向肿瘤的放射性核素的分子放射疗法可以克服这些挑战中的一些挑战，但是迄今为止，还没有一种能够独立于其组织病理学来源而治疗各种儿科恶性肿瘤的癌症选择剂。我们测试了临床级烷基磷脂醚类似物CLR1404、18-（对碘苯基）十八烷基磷酸胆碱作为小儿恶性肿瘤靶向放疗支架的治疗潜力。方法：小儿实体瘤细胞对CLR1404的吸收在体外通过流式细胞术进行了测试，在体内通过PET / CT成像和剂量法进行了测试。在异种移植模型中评估了¹³¹ I-CLR1404的治疗潜力。结果：与正常对照组相比，荧光CLR1404-BODIPY在各种儿科癌症细胞系中均表现出显着的选择性摄取。通过成像证实了使用¹²⁴ I-CLR1404在小鼠异种移植模型中体内靶向肿瘤的摄取。在所有啮齿类小儿异种移植模型中，单剂量静脉内注射¹³¹ I-CLR1404均显着延迟了肿瘤的生长，延长了动物的生存期，同时证明了良好的副作用。结论： ¹³¹I-CLR1404有潜力成为一种靶向肿瘤的放射治疗药物，在儿科肿瘤学中具有广泛的适用性。由于¹³¹ I-CLR1404已进入成人临床试验，因此我们的数据保证了针对这一特别脆弱的患者人群的儿科临床试验的发展。