CMG were employees of Invicro, LLC when the studies were performed. JMS is currently an employee of Biogen Inc. NJA, LK, and ROC are employees of the University of Southampton. MB is an employee of 3D Imaging, and AV was an employee of Biogen Inc. at the time that this work was performed.

Uptake in human brain from a single inhalation was sufficiently rapid that it is plausible that fast rate-of-rise contributes to nicotine dependence in smokers.

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Glucose transport rates are estimated noninvasively in physiological and pathological states by kinetic imaging using PET. The glucose analog most often used is (18)F-labeled 2FDG. Compared with glucose, 2FDG is poorly transported by intestine and kidney. We examined the possible use of 6FDG as a tracer of glucose transport. Lacking a hydroxyl at its 6th position, 6FDG cannot be phosphorylated as 2FDG is. Prior studies have shown that 6FDG competes with glucose for transport in yeast and is actively transported by intestine. Its uptake by muscle has been reported to be unresponsive to insulin, but that study is suspect. We found that insulin stimulated 6FDG uptake 1.6-fold in 3T3-L1 adipocytes and azide stimulated the uptake 3.7-fold in Clone 9 cells. Stimulations of the uptake of 3OMG, commonly used in transport assays, were similar, and the uptakes were inhibited by cyclochalasin B. Glucose transport is by GLUT1 and GLUT4 transporters in 3T3-L1 adipocyte and by the GLUT1 transporter in Clone 9 cells. Cytochalasin B inhibits those transporters. Rats were also imaged in vivo by PET using 6(18)FDG. There was no excretion of (18)F into the urinary bladder unless phlorizin, an inhibitor of active renal transport, was also injected. (18)F activity in brain, liver, and heart over the time of scanning reached a constant level, in keeping with the 6FDG being distributed in body water. In contrast, (18)F from 2(18)FDG was excreted in relatively large amounts into the bladder, and (18)F activity rose with time in heart and brain in accord with accumulation of 2(18)FDG-6-P in those organs. We conclude that 6FDG is actively transported by kidney as well as intestine and is insulin responsive. In trace quantity, it appears to be distributed in body water unchanged. These results provide support for its use as a valid tracer of glucose transport.

Background Animals exposed to sevoflurane during development sustain neuronal cell death in their developing brains. In vivo micro-positron emission tomography (PET)/computed tomography imaging has been utilized as a minimally invasive method to detect anesthetic-induced neuronal adverse effects in animal studies. Methods Neonatal rhesus monkeys (postnatal day 5 or 6, 3 to 6 per group) were exposed for 8 h to 2.5% sevoflurane with or without acetyl-l-carnitine (ALC). Control monkeys were exposed to room air with or without ALC. Physiologic status was monitored throughout exposures. Depth of anesthesia was monitored using quantitative electroencephalography. After the exposure, microPET/computed tomography scans using 18F-labeled fluoroethoxybenzyl-N-(4-phenoxypyridin-3-yl) acetamide (FEPPA) were performed repeatedly on day 1, 1 and 3 weeks, and 2 and 6 months after exposure. Results Critical physiologic metrics in neonatal monkeys remained within the normal range during anesthetic exposures. The uptake of [18F]-FEPPA in the frontal and temporal lobes was increased significantly 1 day or 1 week after exposure, respectively. Analyses of microPET images recorded 1 day after exposure showed that sevoflurane exposure increased [18F]-FEPPA uptake in the frontal lobe from 0.927 ± 0.04 to 1.146 ± 0.04, and in the temporal lobe from 0.859 ± 0.05 to 1.046 ± 0.04 (mean ± SE, P < 0.05). Coadministration of ALC effectively blocked the increase in FEPPA uptake. Sevoflurane-induced adverse effects were confirmed by histopathologic evidence as well. Conclusions Sevoflurane-induced general anesthesia during development increases glial activation, which may serve as a surrogate for neurotoxicity in the nonhuman primate brain. ALC is a potential protective agent against some of the adverse effects associated with such exposures.

The purpose of this study was to determine the clinical feasibility of diagnosing significant coronary artery disease by positron imaging of myocardial perfusion without a cyclotron, using generator-produced rubidium-82 (82Rb). Fifty patients underwent positron emission tomography of the entire heart using a multislice positron camera and intravenous 82Rb or nitrogen-13 ammonia (13NH3) before and after intravenous dipyridamole combined with handgrip stress. Images were read by two observers blinded as to clinical or arteriographic data. Automated quantitative coronary arteriography was obtained for the arteriographic determination of coronary flow reserve, previously demonstrated to be a single integrated measure of stenosis severity accounting for all its geometric dimensions of length, absolute diameter, percent narrowing and asymmetry by quantitative analysis of cine films. Significant coronary artery disease was defined as an arteriographically determined coronary flow reserve of less than 3.0 based on all stenosis dimensions. Any single geometric measure of stenosis severity alone was an inadequate reference standard for comparison with perfusion images. Sensitivity of identifying patients with coronary artery disease having an arteriographically determined coronary flow reserve of less than 3.0 was 95% by positron imaging with a specificity of 100%. The single case that was missed, studied with 13NH3, had a 43% diameter narrowing of a small ramus intermedius off the left coronary artery with no significant narrowing of the major coronary arteries. Positron emission tomography of myocardial perfusion before and after intravenous dipyridamole combined with handgrip stress utilizing generator-produced 82Rb provides sensitive and specific diagnosis of reduced coronary flow reserve due to coronary artery disease in humans.

Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

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