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-(-iodophenyl)octadecyl phosphocholine, as a scaffold for tumor-targeted radiotherapy of pediatric malignancies. 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 ofI-CLR1404 was evaluated in xenograft models. 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 usingI-CLR1404 was confirmed by imaging. Single-dose intravenous injection of I-CLR1404 significantly delayed tumor growth in all rodent pediatric xenograft models and extended animal survival while demonstrating a favorable side effect profile.I-CLR1404 has the potential to become a tumor-targeted radiotherapeutic drug with broad applicability in pediatric oncology. Because I-CLR1404 has entered clinical trials in adults, our data warrant the development of pediatric clinical trials for this particularly vulnerable patient population.

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Objective Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon where symptom severity is worsened 24hr or longer following physical stress, but the pain-related component of PEM is not well characterized. Design Systematic review and meta-analysis Methods Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges’ d effect sizes were aggregated using random effects models and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects using three-level modeling. Results Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small-to-moderate effect indicating higher post-exercise pain in patients than controls (Hedges’ d=0.42; 95% CI: 0.16, 0.67). The mean effect was significantly moderated by pain measurement timepoint (b = -0.19, z = -2.57, P = 0.01) such that studies measuring pain 8-72hr post-exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than those measuring pain 0-2hr post-exercise (d = 0.32, 95% CI = 0.10-0.53). Conclusions People with ME/CFS and FM experience small-to-moderate increases in pain severity following exercise which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.