Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study.

OBJECTIVE: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs. DESIGN: Prospective animal study. SETTING: Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia. SUBJECTS: Four weaned Border-Leicester/Suffolk lambs at 5 months of age. INTERVENTIONS: Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure. MEASUREMENTS AND MAIN RESULTS: Both the HYDRA and AeroNeb Go® produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 µm, range = 0.54-5.41µm) and the AeroNeb Go® (3.07 ± 1.56 µm, range = 0.86-10 µm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung. CONCLUSIONS: Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.

Normal brain metabolism on FDG PET/MRI during childhood and adolescence.

OBJECTIVE: The aim was to investigate normal patterns of brain metabolism determined by F-fluorodeoxyglucose positron emission tomography (FDG PET)/MRI during childhood and adolescence. PATIENTS AND METHODS: A retrospective analysis was carried out on all paediatric patients who underwent FDG PET/MRI at our institution between March 2016 and August 2017. Exclusion criteria were neurological disease, central nervous system metastases, previous chemotherapy/radiotherapy, general anaesthesia/sedation and medications suspected to affect cerebral metabolism. Standardized uptake value (SUV)mean and SUVmax were calculated for 12 brain grey matter regions. Subgroup analysis of childhood (≤10 years old) and adolescence (≥11 years old) was also carried out. RESULTS: From 492 PET/MRI scans, 28 patients (11 children, 17 adolescents) were deemed representative of normal brain metabolism. SUVmean and SUVmax increased with age in all regions. The highest rates of increasing SUVmean were in the thalamus, basal ganglia, frontal lobes, insula and occipital lobes. Higher SUVmean was found in the right frontal, right lateral temporal, right temporal pole, right cingulate/paracingulate, right thalamus, left occipital, left basal ganglia, left insula and left cerebellum compared with the contralateral side. This SUVmean asymmetry was present in both childhood and adolescence in the majority of regions. The highest rates of increasing SUVmax with age were in the occipital lobes, frontal lobes, thalamus and central region. There was no asymmetry in SUVmax in the majority of regions. CONCLUSION: This FDG PET/MRI study shows that normal brain metabolism measured by SUVmean and SUVmax increases with age in all regions, proceeding at different rates between distinct anatomical sites. Our results suggest that there is mild asymmetry in SUVmean, but mostly symmetric SUVmax during normal development.

How common is colonic elongation in children with slow-transit constipation or anorectal retention?

PURPOSE: Colonic elongation is reported as a possible cause for slow colonic transit, as it is observed in patients with slow-transit constipation (STC). This study aimed to determine the frequency of colonic elongation in children with STC or anorectal retention using radioimaging. We hypothesized that transverse colon elongation may occur in patients with STC, whereas sigmoid colon elongates in patients with anorectal retention. METHODS: Nuclear transit scintigraphy performed for chronic constipation (1999-2011) was analyzed qualitatively for elongated transverse colon or sigmoid colon. Three major colonic transit patterns were identified: slow transit in the proximal colon (STC), normal proximal colonic transit with anorectal retention (NT-AR), and rapid proximal transit ± anorectal retention (RT). χ(2) Test was used for statistical analysis (P < .05 significant). RESULTS: From 1999 to 2011, 626 children had nuclear transit scintigraphy. Transverse colon elongation occurred more frequently in STC (73/322, or 23%) compared with NT-AR (9/127, or 7%) and RT (5/177, or 3%; P < .0001). Sigmoid colon elongation was equally common in NT-AR (8/127, or 6%) compared with RT (10/177, or 6%) and STC (14/322, or 4%; P < .9). CONCLUSION: Transverse colon elongation is more common in STC (23%), whereas sigmoid colon elongation is not more common in anorectal retention. Colonic elongation may be the cause or the result of the underlying slow colonic transit.