Abstract Purpose The compound (E)-4-(2-(6-(2-(2-(2-18 F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)- N -methylbenzenamine ([18 F]AV-45) is a novel radiopharmaceutical capable of selectively binding to β-amyloid (Aβ) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [18 F]AV-45 in human subjects. Methods In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0±5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9±13.9 MBq of [18 F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7±13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. Results In vitro autoradiography revealed exquisitely high specific binding of [18 F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12±0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7±78.6 μGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [18 F]AV-45 were 33.8±3.4 μSv/MBq and 19.3±1.3 μSv/MBq, respectively. Conclusion [18 F]AV-45 binds specifically to Aβ in vitro, and is a safe PET tracer for studying Aβ distribution in human brain. The dosimetry is suitable for clinical and research application.
Abstract Background and purpose [18 F]HX4 is a promising hypoxia PET-tracer. Uptake, spatio-temporal stability and optimal acquisition parameters for [18 F]HX4 PET imaging were evaluated in non-small cell lung cancer (NSCLC) patients. Materials and methods [18 F]HX4 PET/CT images of 15 NSCLC patients were acquired 2 h and 4 h after injection (p.i.). Maximum standardized-uptake-value (SUVmax ), tumor-to-blood-ratio (TBRmax ), hypoxic fraction (HF) and contrast-to-noise-ratio (CNR) were determined for all lesions. To evaluate spatio-temporal stability, DICE-similarity and Pearson correlation coefficients were calculated. Optimal acquisition-duration was assessed by comparing 30, 20, 10 and 5 min acquisitions. Results Considerable uptake (TBR >1.4) was observed in 18/25 target lesions. TBRmax increased significantly from 2 h (1.6 ± 0.3) to 4 h p.i. (2.0 ± 0.6). Uptake patterns at 2 h and 4 h p.i. showed a strong correlation ( R = 0.77 ± 0.10) with a DICE similarity coefficient of 0.69 ± 0.08 for the 30% highest uptake volume. Reducing acquisition-time resulted in significant changes in SUVmax and CNR. TBRmax and HF were only affected for scan-times of 5 min. Conclusions The majority of NSCLC lesions showed considerable [18 F]HX4 uptake. The heterogeneous uptake pattern was stable between 2 h and 4 h p.i. [18 F]HX4 PET imaging at 4 h p.i. is superior to 2 h p.i. to reach highest contrast. Acquisition time may be reduced to 10 min without significant effects on TBRmax and HF.
Objective To characterize [11C]‐PBR28 brain uptake using positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). We have previously shown increased [11C]‐PBR28 uptake in the precentral gyrus in a small group of ALS patients. Herein, we confirm our initial finding, study the longitudinal changes, and characterize the gray versus white matter distribution of [11C]‐PBR28 uptake in a larger cohort of patients with ALS and PLS. Methods Eighty‐five participants including 53 with ALS, 11 with PLS, and 21 healthy controls underwent integrated [11C]‐PBR28 PET–magnetic resonance brain imaging. Patients were clinically assessed using the Upper Motor Neuron Burden (UMNB) and the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS‐R). [11C]‐PBR28 uptake was quantified as standardized uptake value ratio (SUVR) and compared between groups. Cortical thickness and fractional anisotropy were compared between groups and correlated with SUVR and the clinical data. [11C]‐PBR28 uptake and ALSFRS‐R were compared longitudinally over 6 months in 10 ALS individuals. Results Whole brain voxelwise, surface‐based, and region of interest analyses revealed increased [11C]‐PBR28 uptake in the precentral and paracentral gyri in ALS, and in the subcortical white matter for the same regions in PLS, compared to controls. The increase in [11C]‐PBR28 uptake colocalized and correlated with cortical thinning, reduced fractional anisotropy, and increased mean diffusivity, and correlated with higher UMNB score. No significant changes were detected in [11C]‐PBR28 uptake over 6 months despite clinical progression. Interpretation Glial activation measured by in vivo [11C]‐PBR28 PET is increased in pathologically relevant regions in people with ALS and correlates with clinical measures. Ann Neurol 2018;83:1186–1197
Technological advances in Magnetic Resonance Imaging (MRI) have provided substantial gains in the sensitivity and specificity of functional neuroimaging. Mounting evidence demonstrates that the hemodynamic changes utilized in functional MRI can be far more spatially and thus neuronally specific than previously believed. This has motivated a push toward novel, high-resolution MR imaging strategies that can match this biological resolution limit while recording from the entire human brain. Although sensitivity increases are a necessary component, new MR encoding technologies are required to convert improved sensitivity into higher resolution. These new sampling strategies improve image acquisition efficiency and enable increased image encoding in the time-frame needed to follow hemodynamic changes associated with brain activation.