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Purpose: [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. Procedures: [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 [F]-FEPPA binding (high-affinity binder (HAB) and low-affinity binder (LAB)), was performed. Results: 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. Conclusions: [F]-FEPPA radiation dose is consistent with other F-labeled radioligands and the Ala147Thr genotype agreed with [F]-FEPPA distribution. [ABSTRACT FROM AUTHOR]

Purpose: We measured the whole-body distribution of IV-injected [C]GSK215083, a new 5-HT antagonist PET tracer, as a function of time in adult subjects, in order to determine the radiation exposure. Procedures: After injection with a single bolus of [C]GSK215083 (range 330-367 MBq; mean 346 MBq), PET emission data were acquired for approximately 120 min in six subjects (three males and three females). Five organs were identified as exhibiting uptake above background. For these, regions of interest were delineated on emission images, and time-activity curves (TAC) generated. Residence times were calculated as the area under the curve of the TAC, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using the computer program OLINDA/EXM 1.0. Results: The mean effective dose averaged over both males and females (±standard deviation) was estimated to be 7.7 ± 1.0 μSv/MBq (male 7.0 ± 0.4; female 8.5 ± 0.6). For the effective dose equivalent, the corresponding values are 7.8 ± 1.2 μSv/MBq (male 6.8 ± 0.5; female 8.9 ± 0.1). The organ receiving the highest dose was the lung, with an average equivalent dose of 25.6 ± 6.9 μSv/MBq (male 20.8 ± 5.6; female 30.4 ± 4.4). Conclusion: The estimated radiation dose for [C]GSK215083 is consistent with those for other neuroreceptor ligands labeled with carbon-11. The somewhat higher dose estimate for females compared to males may reflect the difference in observed residence times and representative differences in the male and female phantoms used for dosimetry calculations. Based on conventionally accepted dose limits, [C]GSK215083 may be used for multiple PET scans in the same subject. [ABSTRACT FROM AUTHOR]

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 COV<10%, across high-uptake ROIs. The excellent identifiability of VT 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. [ABSTRACT FROM AUTHOR]

As a new Russian-Turkish war broke out in 1877, the Romanian political objective of winning the state independence, following a realistic evaluation of the general European conditions, was to be redirected towards a close cooperation with Russia. The Romanian disposition to follow this road, in spite of old anti- Russian feelings, was a significant and a radical political option. Embarking such a relation with Russia, the Romanian politicians experienced both the success of achieving independence and the bitter disappointment of losing a part of the Romania's national territory, but, on the whole, the result of the war was a major success, given circumstances which could not be mastered in their unpredictable change. [ABSTRACT FROM AUTHOR]

The D2 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. [11C]-(+)-PHNO is a PET D2 agonist radioligand and therefore provides a preferential measure of the D2high receptors. In contrast, [11C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D2 high- and low-affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [11C]-(+)-PHNO and [11C]raclopride in volunteers using a within-subject design. Both radioligands accumulated in brain areas rich in D2/D3-receptors. However, [11C]-(+)-PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [11C]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 [11C]raclopride, equal in the ventral-striatum (3.4 vs. 3.3), and higher in the globus pallidus for [11C]-(+)-PHNO (1.8 vs. 3.3). Moreover [11C]-(+)-PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [11C]-(+)-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 D3-over-D2 with [11C]-(+)-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. [ABSTRACT FROM AUTHOR]

Imaging the competition between D2/3 radioligands and endogenous dopamine is so far the only way to measure dopamine release in the living human brain. The dopamine D2 receptor exists in a high (D2high) and a low-affinity state for dopamine. Under physiological conditions, dopamine is expected to bind to D2high only. [11C]-(+)-4-propyl-9-hydroxynaphthoxazine ((+)-PHNO) is the first D2/3 agonist radioligand for positron emission tomography (PET) imaging in humans. Since [11C]-(+)-PHNO is expected to bind preferentially to D2high, 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. [11C]-(+)-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 [11C]-(+)-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 D2/3 agonist radioligand in humans. [11C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D2/3 antagonist radioligands.Neuropsychopharmacology (2008) 33, 279–289; doi:10.1038/sj.npp.1301400; published online 4 April 2007 [ABSTRACT FROM AUTHOR]

Blockade of dopamine D2 receptors remains a common feature of all antipsychotics. It has been hypothesized that the extrastriatal (cortical, thalamic) dopamine D2 receptors may be more critical to antipsychotic response than the striatal dopamine D2 receptors. This is the first double-blind controlled study to examine the relationship between striatal and extrastriatal D2 occupancy and clinical effects. Fourteen patients with recent onset psychosis were assigned to low or high doses of risperidone (1 mg vs 4 mg/day) or olanzapine (2.5 mg vs 15 mg/day) in order to achieve a broad range of D2 occupancy levels across subjects. Clinical response, side effects, striatal ([11C]-raclopride-positron emission tomography (PET)), and extrastriatal ([11C]-FLB 457-PET) D2 receptors were evaluated after treatment. The measured D2 occupancies ranged from 50 to 92% in striatal and 4 to 95% in the different extrastriatal (frontal, temporal, thalamic) regions. Striatal and extrastriatal occupancies were correlated with dose, drug plasma levels, and with each other. Striatal D2 occupancy predicted response in positive psychotic symptoms (r=0.62, p=0.01), but not for negative symptoms (r=0.2, p=0.5). Extrastriatal D2 occupancy did not predict response in positive or negative symptoms. The two subjects who experienced motor side effects had the highest striatal occupancies in the cohort. Striatal D2 blockade predicted antipsychotic response better than frontal, temporal, and thalamic occupancy. These results, when combined with the preclinical data implicating the mesolimbic striatum in antipsychotic response, suggest that dopamine D2 blockade within specific regions of the striatum may be most critical for ameliorating psychosis in schizophrenia.Neuropsychopharmacology (2007) 32, 1209–1215. doi:10.1038/sj.npp.1301242; published online 1 November 2006 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The 0310 ← 0110 parallel Q branch of N2O has been studied at 297 K and over the pressure range 1–130 torr. Absorption spectra were recorded using a high resolution (1.5 MHz or 5 × 10-5 cm-1) and high signal-to-noise (>3500:1) mid-infrared spectrometer based on difference-frequency infrared generation in AgGaS2. In the low-pressure range (1–11 torr) we obtained accurate values for the line strengths, the broadening coefficients, the weak mixing coefficients, and the overall shifting of the branch. The medium pressure results, ranging from 23 to 130 torr, were analyzed by treating the band as a whole, using a relaxation matrix formalism, based on an energy gap scaling law. We find, effectively, that only 36% of the rotationally inelastic collisions are associated with Q branch mixing, the rest presumably being associated with Q–P and Q–R mixing in the same vibrational band. The pressure shifting coefficient of the 0310 ← 0110 Q branch as a whole was also determined and found to be 5.8 × 10-3 cm-1/atm towards lower frequencies. [Copyright &y& Elsevier]

The article looks at the use of genetic technologies in the diagnosis of lymphoid malignancies. It acknowledges genetic technologies for offering valuable diagnosis and prognostic information and a better understanding of disease biology and underlying pathogenetic mechanisms. The application of algorithms and methodologies originating from mathematics and computer science in the use of genetic technologies is discussed.

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., ((c) 2004 American Institute of Physics.)