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Objective: To document symptoms and risk factors of obstructive sleep apnea (OSA) in children who have a parent diagnosed with OSA and compare them to an age and sex matched sample where parents are low risk for OSA., Methods: We recruited 25 children with a parent diagnosed with OSA (P-OSA) and 29 age and gender matched children from the community whose parents scored low risk for OSA (P-NOSA). Comparisons were made using the OSA-18 questionnaire, anthropometric measurements, and mallampati score. Statistical analysis included t-tests for OSA-18 score and BMI measures and non parametric analysis for mallampati score. OSA-18 domain scores were analysed using T-test and Bonferroni correction for multiple comparisons., Results: Fifty-six percent of the P-OSA group had a mallampati score of III/IV compared to 11% in the P-NOSA sample (p = 0.005). There was a significant difference in BMI between the P-OSA sample (mean ± SD 19.5 ± 5.7 kg/m 2 ) and the P-NOSA sample (16.95 ± 2.08 kg/m 2 , p = 0.002). Forty-four percent of P-OSA children were found to be either overweight or obese (BMI z-score). None of the P-NOSA children fell into this category. No significant difference was found between the P-OSA and P-NOSA samples on the OSA-18 score (P-OSA 36.5 ± 8.1, P-NOSA 29.2 ± 9.1, p = 0.07). Five children in the P-OSA sample scored >60 but no P-NOSA children scored >60., Conclusions: This study suggests that children with a parent diagnosed with OSA are more likely to have risk factors of pediatric OSA compared to age and sex matched children of parents without OSA but do not have more symptoms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Preclinical single-photon emission computed tomography (SPECT)/CT imaging studies are hampered by low throughput, hence are found typically within small volume feasibility studies. Here, imaging and image analysis procedures are presented that allow profiling of a large volume of radiolabelled compounds within a reasonably short total study time. Particular emphasis was put on quality control (QC) and on fast and unbiased image analysis., Methods: 2-3 His-tagged proteins were simultaneously radiolabelled by 99m Tc-tricarbonyl methodology and injected intravenously (20 nmol/kg; 100 MBq; n = 3) into patient-derived xenograft (PDX) mouse models. Whole-body SPECT/CT images of 3 mice simultaneously were acquired 1, 4, and 24 h post-injection, extended to 48 h and/or by 0-2 h dynamic SPECT for pre-selected compounds. Organ uptake was quantified by automated multi-atlas and manual segmentations. Data were plotted automatically, quality controlled and stored on a collaborative image management platform. Ex vivo uptake data were collected semi-automatically and analysis performed as for imaging data., Results: >500 single animal SPECT images were acquired for 25 proteins over 5 weeks, eventually generating >3500 ROI and >1000 items of tissue data. SPECT/CT images clearly visualized uptake in tumour and other tissues even at 48 h post-injection. Intersubject uptake variability was typically 13% (coefficient of variation, COV). Imaging results correlated well with ex vivo data., Conclusions: The large data set of tumour, background and systemic uptake/clearance data from 75 mice for 25 compounds allows identification of compounds of interest. The number of animals required was reduced considerably by longitudinal imaging compared to dissection experiments. All experimental work and analyses were accomplished within 3 months expected to be compatible with drug development programmes. QC along all workflow steps, blinding of the imaging contract research organization to compound properties and automation provide confidence in the data set. Additional ex vivo data were useful as a control but could be omitted from future studies in the same centre. For even larger compound libraries, radiolabelling could be expedited and the number of imaging time points adapted to increase weekly throughput. Multi-atlas segmentation could be expanded via SPECT/MRI; however, this would require an MRI-compatible mouse hotel. Finally, analysis of nuclear images of radiopharmaceuticals in clinical trials may benefit from the automated analysis procedures developed.

We evaluated and compared a new bombesin analog [Tyr-Gly5, Nle(14)]-BBN(6-14) conjugated to DOTA or DTPA and radiolabeled with In-111 in low and high GRPR expressing tumor models. Both peptides were radiolabeled with high radiochemical purity and specific activity. In vitro assays on T-47D, LNCaP and PC-3 cells showed that the affinity of peptides is similar and a higher binding and internalization of DOTA-peptide to PC-3 cells was observed. Both peptides could target PC-3 and LNCaP tumors in vivo and both tumor types could be visualized by microSPECT/CT., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: We explored the imaging of bombesin receptors and evaluated the clinical use of [(99m)Tc]Demobesin 4 ([(99m)Tc]DB4) in prostate cancer patients., Procedures: [(99m)Tc]DB4 was prepared according to Good Manufacturing Practice. Patients with prostate cancer underwent serial planar and SPECT imaging up to 3 h after administration. Blood and urine samples were taken to assess pharmacokinetics., Results: [(99m)Tc]DB4 is safe and clears rapidly from the bloodstream via the kidneys resulting in low background activity. The tracer binds strongly to the gastrin-releasing peptide receptor (GRPR) in vivo as indicated by the high uptake in the pancreas seen in all patients. In patients who had undergone hormone therapy, [(99m)Tc]DB4 did not efficiently image metastatic prostate cancer. In contrast, in newly diagnosed patients local disease was visualised., Conclusions: The GRPR is an unsuitable target for imaging refractory prostate cancer but may be useful in untreated disease. [(99m)Tc]DB4 is a promising radiopharmaceutical which merits further exploration in this specific group of patients.

Cholecystokinin-2 (CCK-2) receptors, overexpressed in cancer types such as small cell lung cancers (SCLC) and medullary thyroid carcinomas (MTC), may serve as targets for peptide receptor radionuclide imaging. A variety of CCK and gastrin analogues has been developed, but a major drawback is metabolic instability or high kidney uptake. The minigastrin analogue PP-F11 has previously been shown to be a promising peptide for imaging of CCK-2 receptor positive tumors and was therefore further evaluated. The peptide was conjugated with one of the macrocyclic chelators DOTA, NOTA, or NODAGA. The peptide conjugates were then radiolabeled with either (68)Ga, (64)Cu, or (111)In. All (radio)labeled compounds were evaluated in vitro (IC50) and in vivo (biodistribution and PET/CT and SPECT/CT imaging). IC50 values were in the low nanomolar range for all compounds (0.79-1.51 nM). In the biodistribution studies, (68)Ga- and (111)In-labeled peptides showed higher tumor-to-background ratios than the (64)Cu-labeled compounds. All tested radiolabeled compounds clearly visualized the CCK2 receptor positive tumor in PET or SPECT imaging. The chelator did not seem to affect in vivo behavior of the peptide for (111)In- and (68)Ga-labeled peptides. In contrast, the biodistribution of the (64)Cu-labeled peptides showed high uptake in the liver and in other organs, most likely caused by high blood levels, probably due to dissociation of (64)Cu from the chelator and subsequent transchelation to proteins. Based on the present study, (68)Ga-DOTA-PP-F11 might be a promising radiopharmaceutical for PET/CT imaging of CCK2 receptor expressing tumors such as MTC and SCLC. Clinical studies are warranted to investigate the potential of this tracer.

Carbon nanotubes (CNTs) exhibit unique properties which have led to their applications in the biomedical field as novel delivery systems for diagnosis and therapy purposes. We have previously reported that the degree of functionalization of CNTs is a key factor determining their biological behaviour. The present study broadens the spectrum by investigating the impact of the diameter of CNTs using two series of multi-walled CNTs (MWNTs) with distinct differences in their diameters. Both MWNTs were doubly functionalized by 1,3-dipolar cycloaddition and amidation reactions, allowing the appended functional groups to be further conjugated with radionuclide chelating moieties and antibodies or antibody fragments. All constructs possessed comparable degree of functionalization and were characterized by thermogravimetric analysis, transmission electron microscopy, gel electrophoresis and surface plasmon resonance. The MWNT conjugates were radio-labelled with indium-111, which thereby enabled in vivo single photon emission computed tomography/computed tomography (SPECT/CT) imaging and organ biodistribution study using γ-scintigraphy. The narrow MWNTs (average diameter: 9.2 nm) demonstrated enhanced tissue affinity including non-reticular endothelial tissues compared to the wider MWNTs (average diameter: 39.5 nm). The results indicate that the higher aspect ratio of narrow MWNTs may be beneficial for their future biological applications due to higher tissue accumulation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)