Test-retest reproducibility of cerebral adenosine A(2A) receptor quantification using [C-11]preladenant

Objective To evaluate the reproducibility of cerebral adenosine A(2A) receptor (A(2A)R) quantification using [C-11]preladenant ([C-11]PLN) and PET in a test-retest study. Methods Eight healthy male volunteers were enrolled. Dynamic 90 min PET scans were performed twice at the same time of the day to avoid the effect of diurnal variation. Subjects refrained from caffeine from 12 h prior to scanning, and serum caffeine was measured before radioligand injection. Arterial blood was sampled repeatedly during scanning and the fraction of the parent compound in plasma was determined. Total distribution volume (V-T) was estimated using 1- and 2-tissue compartment models (1-TCM and 2-TCM, respectively) and Logan graphical analysis (Logan plot) (t* = 30 min). Plasma-free fraction (f(P)) of [C-11]PLN was measured and used for correction of V-T values. Distribution volume ratio (DVR) was calculated from V-T of target and reference regions and obtained by noninvasive Logan graphical reference tissue model (LGAR) (t* = 30 min). Absolute test-retest variability (aTRV), and intra-class correlation coefficient (ICC) of V-T and DVR were calculated as indexes of repeatability. Correlation between DVR and serum concentration of caffeine (a nonselective A(2A)R blocker) was analyzed by Pearson's correlation analysis. Results Regional time-activity curves were well described by 2-TCM models. Estimation of V-T by 2-TCM produced some erroneous values; therefore, the more robust Logan plot was selected as the appropriate model. Global mean aTRV was 20% for V-T and 14% for V-T/f(P) (ICC, 0.72 for V-T and 0.87 for V-T/f(P)). Global mean aTRV of DVR was 13% for Logan plot and 10% for LGAR (ICC, 0.70 for Logan plot and 0.81 for LGAR). DVR estimates using LGAR and Logan plot were in good agreement (r(2) = 0.96). Coefficients of variation for V-T, V-T/f(P), DVR (Logan plot), and DVR (LGAR) were 47%, 47%, 27%, and 18%, respectively. Despite low serum caffeine levels, significant concentration-dependent effects on [C-11]PLN binding to target regions were observed (p < 0.01). Conclusions In this study, moderate test-retest reproducibility and large inter-subject differences were observed with [C-11]PLN PET, possibly attributable to competition by baseline amount of caffeine. Analysis of plasma caffeine concentration is recommended during [C-11]PLN PET studies

First clinical assessment of [ 18 F]MC225, a novel fluorine-18 labelled PET tracer for measuring functional P-glycoprotein at the blood-brain barrier

Objective: 5-(1-(2-[18F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen ([18F]MC225) is a selective substrate for P-glycoprotein (P-gp), possessing suitable properties for measuring overexpression of P-gp in the brain. This is the first-in-human study to examine safety, radiation dosimetry and P-gp function at the blood-brain barrier (BBB) of [18F]MC225 in healthy subjects. Methods: [18F]MC225 biodistribution and dosimetry were determined in 3 healthy male subjects, using serial 2 h and intermittent 4 and 6 h whole-body PET scans acquired after [18F]MC225 injection. Dynamic [18F]MC225 brain PET (90 min) was obtained in 5 healthy male subjects. Arterial blood was sampled at various time intervals during scanning and the fraction of unchanged [18F]MC225 in plasma was determined. T1-weighted MRI was performed for anatomical coregistration. Total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1-TCM and 2-TCM, respectively). VT was also estimated using the Logan graphical method (Logan plot) (t* = 20 min). Surrogate parameters without blood sampling (area-under the curve [AUC] of regional time-activity curves [TACs] and negative slope of calculated TACs) were compared with the VT values. Results: No serious adverse events occurred throughout the study period. Although biodistribution implied hepatobiliary excretion, secretion of radioactivity from liver to small intestine through the gallbladder was very slow. Total renal excreted radioactivity recovered during 6 h after injection was 0.9). AUCs of TACs were positively correlated with VT (2-TCM) values (r2: AUC0-60 min = 0.61, AUC0-30 min = 0.62, AUC30-60 min = 0.59, p < 0.0001). Negative slope of SUV TACs was negatively correlated with VT (2-TCM) values (r2 = 0.53, p < 0.0001). Conclusions: This initial evaluation indicated that [18F]MC225 is a suitable and safe PET tracer for measuring P-gp function at the BBB. Keywords: Blood–Brain barrier; Dosimetry; First-in-human; P-glycoprotein; Positron emission tomography

Age and gender effects of 11C-ITMM binding to metabotropic glutamate receptor type 1 in healthy human participants.

We examined possible age- and gender-related changes in bindingof the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) to metabotropicglutamate receptor type 1 (mGluR1) in healthy human brains.Dynamic 11C-ITMM positron emission tomography scans (90 min) with serialarterial blood sampling were performed in 15 young and 24 older healthyadult volunteers. The total distribution volume (VT) of several brainregions was estimated with two-tissue compartment model analysis.The VTs of the cerebellar cortex, parietal cortex, putamen, amygdala, andhippocampus in older adult participants were significantly higher than inyoung participants. The age-related VT increase was only observed in maleparticipants.Our data suggest that an age-dependent increase in mGluR1 availability inseveral brain regions may exist predominantly in males

Centiloid scale analysis for 18F-THK5351 PET imaging in Alzheimer\u27s disease

Purpose: A standardized method for quantification is required for analyzing PET data, but such standards have not been established for tau PET imaging. The Centiloid scale has recently been proposed as a standard method for quantifying amyloid deposition on PET imaging. Therefore, the present study aimed to apply the Centiloid scale to 18F-THK5351 PET imaging in Alzheimer’s disease (AD). Methods: We acquired 18F-THK5351 PET, 11C-PiB PET, and MR images from 47 cognitively normal (CN) individuals and 28 patients with AD with mild to moderate dementia. PET images were spatially normalized to Montreal Neurological Institute space. The PET signals were then normalized using the signal in the reference volume of interest (VOI). Target VOI for specific 18F-THK5351 retention in AD was extracted by voxel-wise comparison of PET images between the 47 CN individuals and 16 AD patients with moderate dementia. Scale anchor points were defined by the CN individuals as 0-anchor points and by that of the average of the typical AD patients as 100-anchor points.Results: Specific retention of 18F-THK5351 was predominant in the angular gyrus, inferior temporal cortex, and parieto-occipital regions in patients with AD. Standardized uptake value ratio (SUVR) of 1.227 and 1.797 were defined as 0- and 100-anchor points, respectively. 18F-THK5351 PET data could be expressed using the Centiloid scale, with the SUVR of the 18F-THK5351 PET images converted to Centiloid using our VOI, the standard Centiloid reference VOI, and the following equation: Centiloid = 169.0 × SUVR–204.6. Conclusion: Centiloid methods can be applied to tau PET imaging using 18F-THK5351

Evaluation of spatial dependence of point spread function-based PET reconstruction using a traceable point-like 22Na source

Abstract Background The point spread function (PSF) of positron emission tomography (PET) depends on the position across the field of view (FOV). Reconstruction based on PSF improves spatial resolution and quantitative accuracy. The present study aimed to quantify the effects of PSF correction as a function of the position of a traceable point-like 22Na source over the FOV on two PET scanners with a different detector design. Methods We used Discovery 600 and Discovery 710 (GE Healthcare) PET scanners and traceable point-like 22Na sources (<1 MBq) with a spherical absorber design that assures uniform angular distribution of the emitted annihilation photons. The source was moved in three directions at intervals of 1 cm from the center towards the peripheral FOV using a three-dimensional (3D)-positioning robot, and data were acquired over a period of 2 min per point. The PET data were reconstructed by filtered back projection (FBP), the ordered subset expectation maximization (OSEM), OSEM + PSF, and OSEM + PSF + time-of-flight (TOF). Full width at half maximum (FWHM) was determined according to the NEMA method, and total counts in regions of interest (ROI) for each reconstruction were quantified. Results The radial FWHM of FBP and OSEM increased towards the peripheral FOV, whereas PSF-based reconstruction recovered the FWHM at all points in the FOV of both scanners. The radial FWHM for PSF was 30–50 % lower than that of OSEM at the center of the FOV. The accuracy of PSF correction was independent of detector design. Quantitative values were stable across the FOV in all reconstruction methods. The effect of TOF on spatial resolution and quantitation accuracy was less noticeable. Conclusions The traceable 22Na point-like source allowed the evaluation of spatial resolution and quantitative accuracy across the FOV using different reconstruction methods and scanners. PSF-based reconstruction reduces dependence of the spatial resolution on the position. The quantitative accuracy over the entire FOV of the PET system is good, regardless of the reconstruction methods, although it depends slightly on the position

Validation of the application of gel beads-based single-cell genome sequencing platform to soil and seawater

Abstract Single-cell genomics is applied to environmental samples as a method to solve the problems of current metagenomics. However, in the fluorescence-activated cell sorting-based cell isolation and subsequent whole genome amplification, the sorting efficiency and the sequence quality are greatly affected by the type of target environment, limiting its adaptability. Here, we developed an improved single-cell genomics platform, named SAG-gel, which utilizes gel beads for single-cell isolation, lysis, and whole genome amplification. To validate the versatility of SAG-gel, single-cell genome sequencing was performed with model bacteria and microbial samples collected from eight environmental sites, including soil and seawater. Gel beads enabled multiple lysis treatments. The genome coverage with model bacteria was improved by 9.1–25%. A total of 734 single amplified genomes were collected from the diverse environmental samples, and almost full-length 16S rRNA genes were recovered from 57.8% of them. We also revealed two marine Rhodobacter strains harboring nearly identical 16S rRNA genes but having different genome contents. In addition, searching for viral sequences elucidated the virus-host linkage over the sampling sites, revealing the geographic distribution and diverse host range of viruses

Impact of γ factor in the penalty function of Bayesian penalized likelihood reconstruction (Q.Clear) to achieve high-resolution PET images

Abstract Background The Bayesian penalized likelihood PET reconstruction (BPL) algorithm, Q.Clear (GE Healthcare), has recently been clinically applied to clinical image reconstruction. The BPL includes a relative difference penalty (RDP) as a penalty function. The β value that controls the behavior of RDP determines the global strength of noise suppression, whereas the γ factor in RDP controls the degree of edge preservation. The present study aimed to assess the effects of various γ factors in RDP on the ability to detect sub-centimeter lesions. Methods All PET data were acquired for 10 min using a Discovery MI PET/CT system (GE Healthcare). We used a NEMA IEC body phantom containing spheres with inner diameters of 10, 13, 17, 22, 28 and 37 mm and 4.0, 5.0, 6.2, 7.9, 10 and 13 mm. The target-to-background ratio of the phantom was 4:1, and the background activity concentration was 5.3 kBq/mL. We also evaluated cold spheres containing only non-radioactive water with the same background activity concentration. All images were reconstructed using BPL + time of flight (TOF). The ranges of β values and γ factors in BPL were 50–600 and 2–20, respectively. We reconstructed PET images using the Duetto toolbox for MATLAB software. We calculated the % hot contrast recovery coefficient (CRChot) of each hot sphere, the cold CRC (CRCcold) of each cold sphere, the background variability (BV) and residual lung error (LE). We measured the full width at half maximum (FWHM) of the micro hollow hot spheres ≤ 13 mm to assess spatial resolution on the reconstructed PET images. Results The CRChot and CRCcold for different β values and γ factors depended on the size of the small spheres. The CRChot, CRCcold and BV increased along with the γ factor. A 6.2-mm hot sphere was obvious in BPL as lower β values and higher γ factors, whereas γ factors ≥ 10 resulted in images with increased background noise. The FWHM became smaller when the γ factor increased. Conclusion High and low γ factors, respectively, preserved the edges of reconstructed PET images and promoted image smoothing. The BPL with a γ factor above the default value in Q.Clear (γ factor = 2) generated high-resolution PET images, although image noise slightly diverged. Optimizing the β value and the γ factor in BPL enabled the detection of lesions ≤ 6.2 mm