The resolution and quantitative accuracy of PET are highly influenced by the reconstruction method. Penalized-likelihood estimation algorithms allow for fully convergent iterative reconstruction, generating a higher image contrast than ordered-subsets expectation maximization (OSEM) while limiting noise. In this study, a type of penalized reconstruction known as block-sequential regularized expectation maximization (BSREM) was compared with time-of-flight OSEM (TOF OSEM). Various strengths of noise penalization factor β were tested along with various acquisition durations and transaxial fields of view (FOVs) with the aim of evaluating the performance and clinical use of BSREM for F-FDG PET/CT, both quantitatively and in a qualitative visual evaluation. Eleven clinical whole-body F-FDG PET/CT examinations acquired on a digital TOF PET/CT scanner were included. The data were reconstructed using BSREM with point-spread function recovery and β-factors of 133, 267, 400, and 533-and using TOF OSEM with point-spread function-for various acquisition times per bed position and various FOVs. Noise level, signal-to-noise ratio (SNR), signal-to-background ratio (SBR), and SUV were analyzed. A masked evaluation of visual image quality, rating several aspects, was performed by 2 nuclear medicine physicians to complement the analysis. The lowest levels of noise were reached with the highest β-factor, resulting in the highest SNR, which in turn resulted in the lowest SBR. A β-factor of 400 gave noise equivalent to TOF OSEM but produced a significant increase in SUV (11%), SNR (22%), and SBR (12%). BSREM with a β-factor of 533 at a decreased acquisition duration (2 min/bed position) was comparable to TOF OSEM at a full acquisition duration (3 min/bed position). Reconstructed FOV had an impact on BSREM outcome measures; SNR increased and SBR decreased when FOV was shifted from 70 to 50 cm. The evaluation of visual image quality resulted in similar scores for reconstructions, although a β-factor of 400 obtained the highest mean whereas a β-factor of 267 was ranked best in overall image quality, contrast, sharpness, and tumor detectability. In comparison with TOF OSEM, penalized BSREM reconstruction resulted in an increased tumor SUV and an improved SNR and SBR at a matched level of noise. BSREM allowed for a shorter acquisition than TOF OSEM, with equal image quality.

AimA close correlation exists between positron emission tomography (PET)-determined histamine H1-receptor occupancy (H1RO) and the incidence of sedation. Antihistamines with H1RO <20% are classified as non-sedating. The objective was to compare the H1RO of bilastine, a second generation antihistamine, with that of hydroxyzine.MethodsThis randomized, double-blind, crossover study used PET imaging with [11C]-doxepin to evaluate H1RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated.ResultsThe mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P < 0.01; mean difference and 95% CI −0.130 [−0.155, 0.105]). There was no significant difference between bilastine and placebo. Overall H1RO by bilastine was significantly lower than that by hydroxyzine (mean value −3.92% vs. 53.95%, P < 0.01; mean difference and 95% CI 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine.ConclusionsA single oral dose of bilastine 20 mg had minimal H1RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine.

HED PET is useful in the detection of pheochromocytomas, providing a high level of accuracy.

No abstract

No abstract

No abstract

Two mitogen-activated protein kinase kinase (MAPK2, also known as MEK) inhibitors were assessed with 18 F-FDG PET in separate phase I clinical studies, clearly illustrating the potential of metabolic imaging for dose, dosing regimen, and compound selection in early-phase trials and utility for predicting nonresponding patients. Methods: 18 F-FDG PET data were collected during 2 independent, phase I, dose-escalation trials of 2 novel MEK inhibitors (RO5126766 and RO4987655). PET acquisition procedures were standardized between the 2 trials, and PET images were analyzed centrally. Imaging was performed at baseline; at cycle 1, day 15; and at cycle 3, day 1. A 10-mmdiameter region of interest was defined for up to 5 lesions, and peak standardized uptake values were determined for each lesion. The relationship between PET response and pharmacokinetic factors (dose and exposure), inhibition of extracellularsignal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells, and anatomic tumor response as measured by Response Evaluation Criteria in Solid Tumors was investigated for both compounds. Results: Seventy-six patients underwent PET, and 205 individual PET scans were analyzed. Strong evidence of biologic activity was seen as early as cycle 1, day 15, for both compounds. 18 F-FDG PET revealed striking differences between the 2 MEK inhibitors at their recommended dose for phase II investigation. The mean amplitude of the decrease in 18 F-FDG from baseline to cycle 1, day 15, was greater for patients receiving RO4987655 than for those receiving RO5126766 (47% vs. 16%, respectively; P 5 0.052). Furthermore, a more pronounced relationship was seen between the change in 18 F-FDG uptake and dose or exposure and phosphorylated ERK inhibition in peripheral blood mononuclear cells in patients receiving RO4987655. For both investigational drugs, PET responses tended to be greatest in patients with melanoma tumors. 18 F-FDG was able to identify early nonresponding patients with a 97% negative predictive value. Conclusion: These data exemplify the role of 18 F-FDG PET for guiding the selection of novel investigational drugs, choosing dose in early-phase clinical development, and predicting nonresponding patients early in treatment.

A 59-year-old man who presented with weight loss and fatigue showed no pathological findings on the contrastenhanced thorax/abdominal CT scan, but a single frontal nodular lesion on the contrast-enhanced cranial CT scan (a) that was considered to represent a single cerebral metastases from an unknown primary.The 18 F-FDG PET scan was performed for staging to exclude a primary tumour, and also a cerebral-MR scan to complete the diagnostic imaging work-up. The PET/CT scan showed intense FDG uptake (b) by the cerebral lesion, but no evidence of any primary tumour. On the basis of the MR imaging findings, a frontal glioblastoma multiforme, well seen on the T1-weighted image (c), was diagnosed. MR imaging also showed additional multiple small meningeal foci surrounding the cisternal areas. PET/CT also showed heterogeneous FDG uptake at the cervical and dorsal spinal cord on the sagittal view (d), which was more easily detectable by increasing the contrast on the same PET scan sagittal view as multiple foci of FDG uptake distributed along the spinal leptomeningeal area (e, arrows) and also on the PET/CT sagittal fusion image (f, arrows). A spinal MRI study confirmed the leptomeningeal infiltration.Although the frontal lesion was surgically treated, the extensive disease led to the patient's death within 30 days.Leptomeningeal metastases from previously untreated cerebral glioblastoma spreading through the cerebrospinal fluid is an uncommon diagnostic finding (more commonly detected on necropsy studies) [1]. Although, to date no report of leptomeningeal metastases from glioblastoma detected by 18 F-FDG PET is available in the literature, there are some cases reports of the ability of FDG PET to detect leptomeningeal metastases [2,3].