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This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COVT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

The D(2) receptors exist in either the high‐ or low‐affinity state with respect to agonists, and while agonists bind preferentially to the high‐affinity state, antagonists do not distinguish between the two states. [(11)C]‐(+)‐PHNO is a PET D(2) agonist radioligand and therefore provides a preferential measure of the D(2) (high) receptors. In contrast, [(11)C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D(2) high‐ and low‐affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [(11)C]‐(+)‐PHNO and [(11)C]raclopride in volunteers using a within‐subject design. Both radioligands accumulated in brain areas rich in D(2)/D(3)‐receptors. However, [(11)C]‐(+)‐PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [(11)C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [(11)C]raclopride, equal in the ventral‐striatum (3.4 vs. 3.3), and higher in the globus pallidus for [(11)C]‐(+)‐PHNO (1.8 vs. 3.3). Moreover [(11)C]‐(+)‐PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [(11)C]‐(+)‐PHNO in the globus pallidus and ventral‐striatum could be the presence of a greater proportion of high‐ vs. low‐affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D(3)‐over‐D(2) with [(11)C]‐(+)‐PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.

The present study focuses on the application of a therapeutic strategy in patients with chronic severe lower limb ischaemia using a plasmid vector encoding the vascular endothelial growth factor (phVEGF165). It has been shown that VEGF promotes neo-vascularization and blood vessel network formation and thus might have the ability to improve blood-flow at the level of the affected limbs. However, little information is available regarding the necessary level of expression of VEGF and its possible related adverse effects. We have subcloned VEGF 165 isoform into pCMV-Script expression vector (Stratagene) under the control of the CMV promoter. Three patients with chronic ischaemia of the lower limb, considered as not suitable for surgical re-vascularization, received intramuscular injection with 0.5 ml saline solution containing 1011 copies of VEGF 165 plasmid. The clinical evolution has been monitored by angiography and estimated by walking time on the rolling carpet (Gardner protocol). Two months after therapy, all three patients showed complete relief of rest pain, improvement of ischaemic ulcer lesions and increased walking distance on the rolling carpet most probably due to appearance of newly formed collateral vessels.

Using both a difference frequency spectrometer and a Fourier transform spectrometer, we have measured transitions in the 12 (2)0--01 (1)0 band of carbon dioxide at room temperature and pressures up to 19 atm. The low-pressure spectra were analyzed using a variety of standard spectral profiles, all with an asymmetric component to account for weak line mixing. For this band, we have been able to retrieve experimental line strengths and the broadening and weak mixing parameters. In this paper we also compare the suitability of the energy-corrected sudden model to predict mixing in the two previously measured Q branches 20 (0)0--01 (1)0, the 11 (1)0--00 (0)0, and the present Q branch of pure CO(2), all at room temperature.

[(18)F]-FEPPA is a translocator protein (18 kDa, TSPO) positron emission tomography (PET) radiotracer. Radiation dosimetry was estimated from the whole body biodistribution, taking into consideration TSPO rs6971 (Ala147Thr) polymorphism.[(18)F]-FEPPA whole body PET scans were acquired for six healthy subjects. Time-activity curves were generated from regions of interest of nine organs, from which normalized accumulated activities were calculated and thus internal dose, using OLINDA/EXM 1.1. Genotyping of rs6971, associated with high- and low-affinity [(18)F]-FEPPA binding (high-affinity binder (HAB) and low-affinity binder (LAB)), was performed.Five subjects exhibited the C/C (HAB) allele, and the other carried the minor allele T/T (LAB). The LAB whole body biodistribution showed highest radioactivity accumulation in bladder, whereas in HABs, the spleen received the highest dose. The effective dose of the single LAB (16.3 μSv/MBq) was 23 % less than the mean of the HABs (21.0 ± 2.9 μSv/MBq). When including all subjects, the effective dose was 20.2 ± 3.0 μSv/MBq.[(18)F]-FEPPA radiation dose is consistent with other (18)F-labeled radioligands and the Ala147Thr genotype agreed with [(18)F]-FEPPA distribution.

TO THE EDITOR: 11C-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is a new PET ligand developed by our group. Binding assays show that (+)-PHNO displays high affinity and selectivity for the D2 receptor ( [1][1] ). Recently, it has been noted that 11C-(+)-PHNO has a preferential affinity and

Imaging the competition between D(2/3) radioligands and endogenous dopamine is so far the only way to measure dopamine release in the living human brain. The dopamine D(2) receptor exists in a high (D(2)(high)) and a low-affinity state for dopamine. Under physiological conditions, dopamine is expected to bind to D(2)(high) only. [(11)C]-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is the first D(2/3) agonist radioligand for positron emission tomography (PET) imaging in humans. Since [(11)C]-(+)-PHNO is expected to bind preferentially to D(2)(high), it should be particularly vulnerable to competition with endogenous dopamine. Nine healthy subjects participated in two PET scans, one after administration of d-amphetamine and one after placebo. [(11)C]-(+)-PHNO PET test re-test variability was determined in 11 healthy subjects. Binding potentials (BPs) were calculated for caudate, putamen, ventral striatum, and globus pallidus. d-Amphetamine led to a significant decrease of [(11)C]-(+)-PHNO BPs in caudate (-13.2%), putamen (-20.8%), and ventral striatum (-24.9%), but not in globus pallidus (-6.5%). d-Amphetamine-induced displacement correlated with serum d-amphetamine levels in all regions but caudate. This is the first report on competition between endogenous dopamine and a D(2/3) agonist radioligand in humans. [(11)C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D(2/3) antagonist radioligands.

We have built a high-resolution and high-signal-to-noise ratio spectrometer for line shape studies of greenhouse gases in the mid infrared. The infrared radiation is generated in a AgGaS2 nonlinear crystal by the well-known difference-frequency method. The choice of crystal is explained, and a brief literature review is presented. With two tunable dye lasers and a type I, 90 degrees phase-matching geometry, the infrared is continuously tunable from 7 to 9 microm when Rhodamine 6G and Sulforhodamine 640 dyes are used. The total infrared power exceeds 30 nW and is limited by both the damage threshold and thermal loading of the crystal. Phase-sensitive detection allows us to reach signal-to-noise ratios in excess of 3500:1 while maintaining an instrumental linewidth of 1.5 MHz. However, we show that the spectrometer may be used to measure the positions of spectral lines within +/-400 kHz.

We calculate the spectral line shape of an isolated line from first principles, assuming that the translational motion is not statistically correlated with the evolution of the optical coherence, i.e., with the broadening. We use the known, realistic potentials for the influence of collisions on the translational motion and on the internal motion. We show that the calculated profiles do not agree, particularly at low pressures, with very precise experimental profiles of the P(2) line of CO in a bath of Ar. We establish that the source of the disagreement lies in the assumption of uncorrelated effects of collisions on the translational motion and the optical coherence associated with the internal degrees of freedom.

High‐resolution measurements of the Π ← Π Q‐branch of pure N2O near 1160 cm−1 were made using a difference‐frequency spectrometer with resolution of 5 × 10−5 cm−1 and a signal‐to‐noise ratio of 2000:1. Lines Q18F through Q12E have been recorded in a single scan, at room temperature and at pressures ranging from 1 to 130 torr. The spectra are analyzed up to 23 torr on a line‐by‐line basis using a hard collision profile including Dicke narrowing and line mixing. Since the separation of the central lines of this double‐sided Q‐branch is of the same order of magnitude with the collisional broadening, line mixing is considered in the analysis even at 1 torr and its dependence with pressure is studied.

A practical matrix‐based formalism for solving the master equation for a spectral line is applied to the P(2) transition in the fundamental band of carbon monoxide perturbed by argon. The method assumes that the effect of intermolecular collisions on the internal relaxation of the molecules is uncorrelated with the effect of those collisions on the translational motion of the molecules. Comparison with high‐resolution line shape measurements reveals that at low pressures, the omission of statistical correlation leads to a miscalculation of the shape of the line.

One aspect of the complexity of mid- and high-harmonic generation in high-intensity laser-plasma interactions is that nonlinear hydrodynamics is virtually always folded together with the nonlinear optical conversion process. We have partly dissected this issue in picosecond and subpicosecond interactions with preformed plasma gradients, imaging and spectrally resolving low- and mid-order harmonics. We describe spatial breakup of the picosecond beam in preformed plasmas, concomitant broadening and breakup of the harmonic spectrum, presumably through self-phase modulation, together with data on the sensitivity of harmonics production efficiency to the gradient or extent of preformed plasma. Lastly, we show preliminary data of regular Stokes-like and anti-Stokes-like satellites to the harmonics, accompanied by modification of the forward-scattered beam.

New line shape calculations for CO buffered by Ar are compared to high‐resolution measurements from a difference‐frequency laser spectrometer, over a range of thermodynamic conditions relevant to the atmosphere. The calculations are based on solving the quantum kinetic (i.e. transport/relaxation) equation for the molecules within the impact approximation, and rely on the commonly used MOLSCAT and MOLCOL codes to determine the speed‐dependent collisional relaxation rate. Velocity‐changing effects are treated classically using a rigid sphere potential. The comparison initially reveals that the experimental profiles exhibit only 10% to 30% of the expected Dicke narrowing, which leads us to reevaluate our understanding of the narrowing process. A more subtle aspect of the disagreement between theory and experiment draws our attention to an assumption implicit in the calculation of the collisional relaxation rate: the assumption of a Maxwellian form for the velocity dependence of the off‐diagonal elements of the density matrix (i.e. the optical coherences). This assumption allows for an analytical simplification of the problem, but eliminates velocity‐changing effects (so that they must be added back in using a supplementary classical calculation, which is based here on a rigid sphere interaction). We find that the removal of the above‐mentioned assumption should allow for accurate and fully quantum mechanical (but numerical) line shape calculations for systems like CO‐Ar on existing computers.