Meta-[¹²³I]iodobenzylguanidine ([¹²³I]MIBG) scintigraphy with SPECT/CT is the standard of care for diagnosing and monitoring neuroblastoma. Replacing [¹²³I]MIBG with the new PET tracer meta-[¹⁸F]fluorobenzylguanidine ([¹⁸F]MFBG) and further improving sensitivity and reducing noise in a new long-axial-field-of-view (LAFOV) PET/CT scanner enable increased image quality and a faster acquisition time, allowing examinations to be performed without sedation or general anesthesia (GA). Focusing on feasibility, we present our first experience with [¹⁸F]MFBG LAFOV PET/CT and compare it with [¹²³I]MIBG scintigraphy plus SPECT/CT for imaging in neuroblastoma in children. Methods: A pilot of our prospective, single-center study recruited children with neuroblastoma who were referred for [¹²³I]MIBG scintigraphy with SPECT/CT. Within 1 wk of [¹²³I]MIBG scintigraphy and SPECT/low-dose CT, [¹⁸F]MFBG LAFOV PET/ultra–low-dose CT was performed 1 h after injection (1.5–3 MBq/kg) without sedation or GA, in contrast to the 24-h postinjection interval needed for scanning with [¹²³I]MIBG, the 2- to 2.5-h acquisition time, and the GA often needed in children less than 6 y old. Based on the spirocyclic iodonium-ylide precursor, [¹⁸F]MFBG was produced in a fully automated good manufacturing practice–compliant procedure. We present the feasibility of the study. Results: In the first paired scans of the first 10 children included (5 at diagnosis, 2 during treatment, 2 during surveillance, and 1 at relapse), [¹⁸F]MFBG PET/CT scan showed a higher number of radiotracer-avid lesions in 80% of the cases and an equal number of lesions in 20% of the cases. The SIOPEN score was higher in 50% of the cases, and the Curie score was higher in 70% of the cases. In particular, intraspinal, retroperitoneal lymph node, and bone marrow involvement was diagnosed with much higher precision. None of the children (median age, 1.6 y; range, 0.1–7.9 y) had sedation or GA during the PET procedure, whereas 80% had GA during [¹²³I]MIBG scintigraphy with SPECT/CT. A PET acquisition time of only 2 min without motion artifacts was the data requirement of the 10-min acquisition time for reconstruction to provide a clinically useful image. Conclusion: This pilot study demonstrates the feasibility of performing [¹⁸F]MFBG LAFOV PET/CT for imaging of neuroblastoma. Further, an increased number of radiotracer-avid lesions, an increased SIOPEN score, and an increased Curie score were seen on [¹⁸F]MFBG LAFOV PET/CT compared with [¹²³I]MIBG scintigraphy with SPECT/CT, and GA and sedation was avoided in all patients. Thus, with a 1-d protocol, a significantly shorter scan time, a higher sensitivity, and the avoidance of GA and sedation, [¹⁸F]MFBG LAFOV PET/CT shows promise for future staging and response assessment and may also have a clinical impact on therapeutic decision-making for children with neuroblastoma. Visual Abstract

Purpose. The purpose of this paper is to evaluate a new PET tracer ⁶⁴Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H727) were administered ⁶⁴Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin , integrin , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM. Results. Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin , integrin and VEGF-A (all ). The whole body effective dose for humans was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. ⁶⁴Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use.

(64)Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of (64)Cu-DOTA-AE105. Five mice received iv tail injection of (64)Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22 h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22 h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another (64)Cu-DOTA peptide-based tracer, (64)Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using (64)Cu-DOTA-TATE. Human estimates of (64)Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918 mSv/MBq) followed by the liver (0.0815 mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04 mSv/MBq. The mean effective whole-body dose of (64)Cu-DOTA-AE105 was estimated to be 0.0317 mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for (64)Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252 mSv/Mbq, Observed value: 0.0315 mSv/MBq) thus validating our approach for human dosimetry estimation. Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of (64)Cu-DOTA-AE105.

Patients with acute respiratory failure are at risk of deterioration during prehospital transport. Ventilatory support with continuous positive airway pressure (CPAP) can be initiated in the prehospital setting. The objective of the study is to evaluate adherence to treatment and effectiveness of CPAP as an addition to standard care. In North Denmark Region, patients with acute respiratory failure, whom paramedics assessed as suffering from acute cardiopulmonary oedema, acute exacerbation of chronic obstructive pulmonary disease or asthma were treated with CPAP using 100 % O2 from 1 March 2014 to 3 May 2015. Adherence to treatment was evaluated by number of adverse events and discontinuation of treatment. Intensive care admissions and mortality were reported in this cohort. Effectiveness was evaluated by changes in peripheral oxygen saturation (SpO2) and respiratory rate during transport and compared to a historical control (non-CPAP) group treated with standard care only. Values were compared by hypothesis testing and linear modelling of SpO2 on arrival at scene and ΔSpO2 stratified according to treatment group. In fourteen months, 171 patients were treated with CPAP (mean treatment time 35 ± 18 min). Adverse events were reported in 15 patients (9 %), hereof six discontinued CPAP due to hypotension, nausea or worsening dyspnoea. One serious adverse event was reported, a suspected pneumothorax treated adequately by an anaesthesiologist called from a mobile emergency care unit. Among CPAP patients, 45 (27 %) were admitted to an intensive care unit and 24 (14 %) died before hospital discharge. The non-CPAP group consisted of 739 patients. From arrival at scene to arrival at hospital, CPAP patients had a larger increase in SpO2 than non-CPAP patients (87 to 96 % versus 92 to 96 %, p < 0.01) and a larger decrease in respiratory rate (32 to 25 versus 28 to 24 breaths/min, p < 0.01). In a linear model, CPAP was superior to non-CPAP in patients with initial SpO2 ≤90 % (p < 0.05). One CPAP patient (0.6 %) and eight non-CPAP patients (1.1 %) were intubated in the prehospital setting. The study design reflects the daily prehospital working environment including long transport timesand paramedics educated in treating symptoms of acute respiratory failure, rather than treating one specific diagnosis. The study population was included consecutively and few patients were lost to follow-up. However, the study was too small to allow assessment of any effect of prehospital CPAP on mortality, nor could the effectiveness in specific disease conditions be examined. In an emergency medical service including physician backup, adherence to CPAP treatment administered by paramedics was high and treatment was effective in patients with acute respiratory failure.

Herein, we present a one-step labeling procedure of N-succinimidyl-4-[¹⁸F]-fluorobenzoate ([¹⁸F]SFB) starting from spirocyclic iodonium ylide precursors. Precursor syntheses succeeded via a simple one-pot, two-step synthesis sequence, in yields of approximately 25%. Subsequent ¹⁸F-nucleophilic aromatic labeling was performed, and radiochemical incorporations (RCCs) from 5–35% were observed. Purification could be carried out using HPLC and subsequent solid phase extraction. Radiochemical purity (RCP) of >95% was determined. The total synthesis time, including purification and formulation, was no longer than 60 min. In comparison to the established 3-step synthesis route of [¹⁸F]SFB, this one-step approach avoids formation of volatile radioactive side-products and simplifies automatization.