32 research outputs found
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
Determination of Ultra-Trace Scandium, Yttrium and Rare-Earth Elements in High-Purity Iron by High-Resolution Inductively Coupled Plasma-Mass Spectrometry
The determination of trace amounts of scandium, yttrium and Rare-Earth elements (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) in high-purity iron by high-resolution Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) was investigated. In using high-resolution ICP-MS, isotopes with overlapped mass numbers are distinguishable and all the rare-earth elements are simultaneously determined in one scanning. For the separation of iron, a liquid-liquid extraction method using 4-methyl-2-pentanone was investigated. Matrix iron could be transferred to the organic phase and analytes remained in the inorganic phase. Moreover, ng levels of these elements in high-purity iron could be determined. The proposed method could be applied to determination of ultra-trace of scandium, yttrium and Rare-Earth elements in high-purity iron, and ng.g–1 (ppb) or under ppb level detection limits were obtained
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