Identification of safe and valid PET radioligands for metabotropic glutamate receptor, type 5 (mGluR5), is essential to measure changes in brain mGluR5 in neuropsychiatric disorders, to confirm central mGluR5 occupancy of drug candidates, and to guide dose selection for obtaining an optimum therapeutic window. Here we present the results of a first-inhuman study assessing the safety and effectiveness of a novel PET radiopharmaceutical, 18 F-3-fluoro-5-[(pyridin-3-yl)ethynyl] benzonitrile ( 18 F-FPEB), for quantifying regional brain concentrations of mGluR5. Methods: Quantification of whole-body biokinetics was conducted in 6 healthy adults (3 men and 3 women). The radiation safety profile was estimated with OLINDA/EXM software. Subsequently, pairs of dynamic brain scans were obtained for 11 healthy men to identify optimal methods for derivation of regional distribution volume and binding potential and to determine the repeatability of measurement. Results: The whole-body effective radiation dose was approximately 17 mSv/MBq (62 mrem/mCi), with the gallbladder receiving the highest dose of 190 mSv/MBq. In brain studies, time-activity curves showed high accumulation in the insula/caudate nucleus, moderate uptake in the thalamus, and the lowest concentration in the cerebellum/pons. The plasma reference graphical analysis method appeared optimal for 18 F-FPEB; it showed acceptable test-retest variability of nondisplaceable binding potential (,10%) and identified the highest nondisplaceable binding potential values (from ;0.5 in the globus pallidus to ;3.5 in the insula) for target regions. Safety assessments revealed no clinically meaningful changes in vital signs, electrocardiogram, or laboratory values. Conclusion: 18 F-FPEB is safe and well tolerated, and its regional cerebral distribution is consistent with previous reports in the literature for metabotropic glutamate receptors. The repeatability of measurement suggests that 18 F-FPEB is suitable for quantifying mGluR5 in humans.

Prevalence and intensity of FDG uptake in large arteries generally increases with aging. Increased FDG uptake likely represents the presence of active inflammatory process of atherosclerotic plaque. The magnitude of inflammation within the wall of the large arteries increases with aging.

No abstract

Our study demonstrates that FDG PET/CT has high sensitivity and accuracy and a substantial complementary value to BMB in the initial diagnosis of pediatric lymphoma, and should be employed as a first-line study.

BackgroundTrabecular bone score (TBS), which has been proposed to be used in complementary with bone mineral density (BMD) to improve the assessment of fracture risk, is negatively associated with body mass index (BMI). The effect of soft tissue, which is expected to be thicker in subjects with high BMI, on TBS was studied using three scan types: Hologic with fast array mode (Hfa), Hologic with high definition mode (Hhd), and GE-Lunar iDXA.MethodsA spine phantom provided by Hologic for routine quality control procedure was scanned using three scan types: Hfa, Hhd, and iDXA. The phantom was scanned with an overlying soft tissue equivalent material (bolus used in radiotherapy) of 0 (without), 1, 2.5, 3.5, 5 and 7.5 cm thick. For each setting, 30 acquisitions were performed in the same way as for the quality control procedure. TBS was calculated using TBS iNsight® software version 2.1 on the same regions of interest as those used for lumbar spine BMD.ResultsMean ± SD TBS of the phantom (without overlying soft tissue) were 1.379 ± 0.018, 1.430 ± 0.009, and 1.423 ± 0.005 using Hfa, Hhd, and iDXA, respectively. A one-way repeated measures ANOVA showed that there were statistically differences in TBS due to different thicknesses of soft tissue equivalent materials for all three scan types (p < 0.001). A Tukey post-hoc test revealed that the decrease in TBS was statistically significant (p < 0.001) when the soft tissue thickness was 1 cm (−0.0246 ± 0.0044, −0.0319 ± 0.0036, and −0.0552 ± 0.0015 for Hfa, Hhd, and iDXA, respectively). Although to a lesser degree, the effects were also statistically significant for BMD (p < 0.05): an increase for Hfa and Hhd but a decrease for iDXA. However, these changes did not exceed the least significant change (LSC) derived from patients.ConclusionsIncreased soft tissue thickness results in lower TBS value. Although BMD is also affected, it is unlikely to pose a clinical problem because the change is unlikely to exceed the patient-derived LSC.