Biodistribution and radiation dosimetry of the carbonic anhydrase IX imaging agent [(18) F]VM4-037 determined from PET/CT scans in healthy volunteers.

Purpose: [(18) F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [(18) F]VM4-037 using whole-body PET/CT scans in healthy human volunteers.

Procedures: Successive whole-body PET/CT scans were performed after intravenous injection of [(18) F]VM4-037 in four healthy humans.

Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy.

Objectives: The PAREPET (Prediction of ARrhythmic Events with Positron Emission Tomography) study sought to test the hypothesis that quantifying inhomogeneity in myocardial sympathetic innervation could identify patients at highest risk for sudden cardiac arrest (SCA).

Background: Left ventricular ejection fraction (LVEF) is the only parameter identifying patients at risk of SCA who benefit from an implantable cardiac defibrillator (ICD).

Methods: We prospectively enrolled 204 subjects with ischemic cardiomyopathy (LVEF ≤35%) eligible for primary prevention ICDs.

Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.

Unlabelled: 2-((2S,5R,8S,11S)-5-benzyl-8-(4-((2S,3R,4R,5R,6S)-6-((2-(4-(3-(18)F-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)butyl)-11-(3-guanidinopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid ((18)F-RGD-K5) has been developed as an α(v)β(3) integrin marker for PET. The purpose of this study was to determine the biodistribution and estimate the radiation dose from (18)F-RGD-K5 using whole-body PET/CT scans in monkeys and humans.

Methods: Successive whole-body PET/CT scans were obtained after intravenous injection of (18)F-RGD-K5 in 3 rhesus monkeys (167 ± 19 MBq) and 4 healthy humans (583 ± 78 MBq).

Should I stay or should I go? Motivational profiles of Danish seafaring officers and non-officers.

Background: Other studies have shed light on specific types of seafarers' job stressors and job satisfaction. However, so far there have not been any systematic attempts to capture the motivational profile of seafarers when it comes to both work demands and work resources. The purpose of this study is to explore the motivational profiles of seafarers in the Danish merchant fleet by identifying factors which motivate or demotivate seafarers to stay in their specific profession.

Performance effects and subjective disturbance of speech in acoustically different office types--a laboratory experiment.

Unlabelled: This study examined how the intelligibility of irrelevant speech, determined with the Speech Transmission Index (STI), affects demanding cognitive task performance. Experiment was carried out in a laboratory that resembled an open-plan office. Three speech conditions were tested corresponding to a private office (STI = 0.

Prediction of arrhythmic events with positron emission tomography: PAREPET study design and methods.

Background: In medically-treated patients with ischemic cardiomyopathy, myocardial viability is associated with a worse prognosis than scar. The risk is especially great with hibernating myocardium (chronic regional dysfunction with reduced resting flow), and the excess mortality appears to be due to sudden cardiac death (SCD). Hibernating myocardium also results in sympathetic nerve dysfunction, which has been independently associated with risk of SCD.

Regional 11C-hydroxyephedrine retention in hibernating myocardium: chronic inhomogeneity of sympathetic innervation in the absence of infarction.

Unlabelled: We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium.

Brain blood flow in the nitroglycerin (GTN) model of migraine: measurement using positron emission tomography and transcranial Doppler.

Nitroglycerin has been widely used as a model of experimental migraine. Studies combining measurement of flow velocity using transcranial Doppler (TCD) concurrently with measures of cerebral blood flow (CBF) are uncommon. We report the results of a study combining TCD and positron emission tomography (PET).

The effect of age and density of the breast on the sensitivity of breast cancer diagnostic by mammography and ultasonography.

Purpose: We studied which, age of the patient or density of the breast accounts for the sensitivity of mammography and ultrasonography (US). Furthermore we studied whether the overall impression on the density of the breast or the density in tumour area accounts for the sensitivity of mammography and ultrasonography.

Materials And Methods: The material consisted of 572 consecutive histologically and 5 cytologically verified breast cancer cases.

PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma.

Pheochromocytomas are potentially curable causes of hypertension. These tumors are currently located by functional imaging with meta-iodobenzylguanidine (MIBG), usually labeled with 131I, or anatomic imaging (computed tomography, magnetic resonance). Hydroxyephedrine (HED) is a newly developed radiotracer that concentrates in adrenergic nerve terminals.

Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

Positron emission tomography in combination with the newly introduced catecholamine analogue [11C]hydroxyephedrine ([11C]HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [11C]HED retention was compared to regional blood flow as assessed by rubidium-82.

Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging.

Carbon-11-meta-hydroxyephedrine is a new radiotracer developed for mapping the sympathetic nerves of the heart. Carbon-11-meta-hydroxyephedrine is synthesized by direct N-methylation of metaraminol with [11C]methyl iodide in dimethyl formamide/dimethyl sulfoxide and purified by semi-preparative reversed-phase HPLC. Total synthesis time is 45 min from end-of-bombardment.

Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography.

The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine.

Imaging the dopamine uptake site with ex vivo [18F]GBR 13119 binding autoradiography in rat brain.

We studied the binding of [18F]GBR 13119 (1-[[(4-[18F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum greater than nucleus accumbens = olfactory tubercle greater than substantia nigra = ventral tegmental area greater than other areas. Binding was blocked by prior injection of dopamine uptake blockers but not by injection of dopamine receptor antagonists or drugs that bind to the dialkylpiperazine site.

Mouse brain distribution of a carbon-11 labeled vesamicol derivative: presynaptic marker of cholinergic neurons.

The regional mouse brain distribution of a new carbon-11 labeled derivative of vesamicol, [11C]-5-(N-methylamino)benzovesamicol [( 11C]MABV) is reported. Radiotracer concentrations in vivo are in the rank order of striatum greater than cortex greater than hippocampus greater than hypothalamus greater than cerebellum, consistent with reported distributions of other presynaptic cholinergic neuronal markers. In time course studies, striatum/cerebellum and cortex/cerebellum ratios for (-)-[11C]MABV continue to increase to values of 13 and 5, respectively, 75 min after i.

Regional brain distribution of [18F]GBR 13119, a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice.

We have examined the regional brain distribution of [18F]GBR 13119 (18F: beta +, T1/2 = 110 min), a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice. High levels of binding are observed in the striatum of both species, with striatum/cerebellum ratios of 3-4 at 60 min after injection of the radiotracer. Striatum radioactivity and striatum/cerebellum ratios are more than 50% reduced in C57BL/6 mice treated chronically with the neurotoxin MPTP.

Biodistribution, dosimetry, metabolism and monkey PET studies of [18F]GBR 13119. Imaging the dopamine uptake system in vivo.

The in vivo characteristics of a new radiotracer, [18F]GBR 13119, have been examined. Full body biodistribution in rats has been determined and the expected human dosimetry calculated. Pharmacological specificity of in vivo regional brain distribution in rats was examined.

Synthesis and regional mouse brain distribution of [11C]nisoxetine, a norepinephrine uptake inhibitor.

Nisoxetine, a selective and high affinity (IC50 = 1 nM) inhibitor of NE reuptake, has been radiolabeled in high specific activity (greater than 600 Ci/mmol) by the alkylation of the nor-methyl precursor with [11C]CH3I. Synthetic yields are good (40-60% from [11C]methyl iodide, corrected for decay, 20 min synthesis), with the product purified by HPLC. In vivo studies of regional brain distribution in CD-1 mice show uptake and retention of tracer in the cortex, striatum, hypothalamus and thalamus, with the highest levels in the hypothalamus and cortex.

Synthesis of [18F]GBR13119, a presynaptic dopamine uptake antagonist.

[18F]GBR13119 (1-[(4-[18F]fluorophenyl)-(phenyl)methoxy]ethyl-4-(3-phenylpropyl) piperazine) has been prepared in no carrier added form by a four-step synthesis from [18F]fluoride. Isolated yields are 7-10% (uncorrected) in a synthesis time of 120 min. The product is obtained in high specific activity (greater than 1000 Ci/mmol) and high radiochemical purity (greater than 99%) without chromatographic purification.