Biomedical subjects

Bengt Långström

Publications and source records attributed to Bengt Långström.

At least 19 recordsLinked to original sources

PubMed2006

Hypothalamic blood flow correlates positively with stress-induced cortisol levels in subjects with social anxiety disorder.

OBJECTIVE: The adrenal excretion of cortisol in animals is dependent on the production of corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus. The a priori hypothesis of this study was that hypothalamic regional cerebral blood flow (rCBF) would correlate positively with salivary cortisol levels in patients with social anxiety disorder (SAD) during anxiety provocation. Another objective was to evaluate whether salivary cortisol levels correlated with rCBF in other brain areas. METHOD: Regional CBF was measured with oxygen-15-labeled water and positron emission tomography during a public speaking task before and after placebo treatment in 12 subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined SAD. Cortisol concentrations in saliva were measured 15 minutes after the task. The a priori hypothesis of a salivary cortisol-dependent activation of the hypothalamus was studied with region-of-interest analysis. In addition, the covariation between rCBF and salivary cortisol was studied in the whole brain using the general linear model. RESULTS: The region-of-interest analysis revealed a positive correlation between salivary cortisol and hypothalamic rCBF. In the whole brain analysis, a positive covariation between rCBF and salivary cortisol levels was found in a midbrain cluster encompassing the hypothalamus with its statistical maximum in the mamillary bodies. Negative covariations were observed in the medial prefrontal cortex as well as in the motor and premotor cortices. CONCLUSION: Like in animals, stress-induced cortisol excretion in humans may be inhibited by activity in the medial prefrontal cortex and enhanced by activity in the hypothalamus.

Adult↗

PubMed2006

Symptom provocation in specific phobia affects the substance P neurokinin-1 receptor system.

BACKGROUND: Animal studies demonstrate that stress and negative affect enhance the release of the neuropeptide substance P (SP), which binds to the neurokinin 1 (NK1) receptor. This positron emission tomography (PET) study evaluated how the activity in the SP-NK1 receptor system in the amygdala was affected by fear provocation in subjects with specific phobia. METHODS: Sixteen adult women with DSM-IV-defined specific phobia for either snakes or spiders but not both viewed pictures of feared and non-feared animals while being PET-scanned for 60 min with the highly specific NK1 receptor antagonist [(11)C]GR205171 as the labeled PET tracer. RESULTS: The uptake of the labeled NK1 receptor antagonist was significantly reduced in the right amygdala during phobic stimulation. In the left amygdala no significant differences were found between phobic and non-phobic conditions. There was a negative correlation in the right, but not left, amygdala between subjective anxiety ratings and NK1 tracer binding. CONCLUSIONS: Fear provocation affects the SP-NK1 receptor system in the right amygdala. This reflects reduced NK1 receptor availability during fear and could mirror an increased release of endogenous substance P.

Adult↗

PubMed2006

A new application of pre-normalized principal component analysis for improvement of image quality and clinical diagnosis in human brain PET studies--clinical brain studies using [11C]-GR205171, [11C]-L-deuterium-deprenyl, [11C]-5-Hydroxy-L-Tryptophan, [11C]-L-DOPA and Pittsburgh Compound-B.

Principal component analysis (PCA) is one of the most applied multivariate image analysis tool on dynamic Positron Emission Tomography (PET). Independent of used reconstruction methodologies, PET images contain correlation in-between pixels, correlations in-between frame and errors caused by the reconstruction algorithm including different corrections, which can affect the performance of the PCA. In this study, we have investigated a new approach of application of PCA on pre-normalized, dynamic human PET images. A range of different tracers have been used for this purpose to explore the performance of the new method as a way to improve detection and visualization of significant changes in tracer kinetics and to enhance the discrimination between pathological and healthy regions in the brain. We compare the new results with the results obtained using other methods. Images generated using the new approach contain more detailed anatomical information with higher quality, precision and visualization, compared with images generated using other methods.

Antiemetics↗

PubMed2006

5-Hydroxy-L-[beta-11C]tryptophan versus alpha-[11C]methyl-L-tryptophan for positron emission tomography imaging of serotonin synthesis capacity in the rhesus monkey brain.

The purpose of this study was to compare two positron emission tomography (PET) tracers that were developed to follow serotonin (5HT) synthesis by performing sequential PET scanning of the same rhesus monkey (n=4) on the same day. alpha-[11C]Methyl-L-tryptophan ([11C]AMT) and 5-Hydroxy-L-[beta-11C]tryptophan ([11C]HTP) are substrates in the first and second enzymatic steps, respectively, in the biosynthesis of 5HT. Regional net accumulation rate constants were derived from kinetic (two-tissue compartment model with irreversible tracer trapping) and graphic (Patlak) analyses, using the arterial plasma concentrations as input. The kinetic data analysis showed that the rate constant for the transfer of [11C]HTP into the brain (K1) was higher than that for [11C]AMT in the striatum and thalamus but was similar in other brain regions. The rate constant for tracer trapping (k3) was also higher for [11C]HTP than for [11C]AMT in the striatum (0.046+/-0.024 versus 0.019+/-0.006 min(-1)) and thalamus (0.039+/-0.013 versus 0.016+/-0.007 min(-1)). In agreement with previously reported regional HTP accumulation rates, the net accumulation rate constant (K(acc)) for [11C]HTP was also higher in these regions than in other brain regions; this is in contrast to the uniform distribution of [11C]AMT K(acc) values. This suggests that the regional net accumulation rates obtained with these two PET tracers will be of different magnitude, which might be related to the activity of each targeted enzyme.

5-Hydroxytryptophan↗

PubMed2006

Predicting brain concentrations of drug using positron emission tomography and venous input: modeling of arterial-venous concentration differences.

OBJECTIVE: In a positron emission tomography (PET) study, the concentrations of the labeled drug (radiotracer) are often different in arterial and venous plasma, especially immediately following administration. In a PET study, the transfer of the drug from plasma to brain is usually described using arterial plasma concentrations, whereas venous sampling is standard in clinical pharmacokinetic studies of new drug candidates. The purpose of the study was to demonstrate the modeling of brain drug kinetics based on PET data in combination with venous blood sampling and an arterio-venous transform (T(av)). METHODS: Brain kinetics (C(br)) was described as the convolution of arterial plasma kinetics (C(ar)) with an arterial-to-brain impulse response function (T(br)). The arterial plasma kinetics was obtained as venous plasma kinetics (C(ve)) convolved with the inverse of the arterio-venous transform (T(av) (-1)). The brain kinetics was then given by C(br)=C(ve)*T(av) (-1)*T(br). This concept was applied on data from a clinical PET study in which both arterial and venous plasma sampling was done in parallel to PET measurement of brain drug kinetics. The predictions of the brain kinetics based on an arterial input were compared with predictions using a venous input with and without an arterio-venous transform. RESULTS: The venous based models for brain distribution, including a biexponential arterio-venous transform, performed comparably to models based on arterial data and better than venous based models without the transform. It was also shown that three different brain regions with different shaped concentration curves could be modeled with a common arterio-venous transform together with an individual brain distribution model. CONCLUSION: We demonstrated the feasibility of modeling brain drug kinetics based on PET data in combination with venous blood sampling and an arterio-venous transform. Such a model can in turn be used for the calculation of brain kinetics resulting from an arbitrary administration mode by applying this model on venous plasma pharmacokinetics. This would be an important advantage in the development of drugs acting in the brain, and in other circumstances when the effect is likely to be closer related to the brain than the plasma concentration.

Adult↗

PubMed2006

Duration and degree of cyclosporin induced P-glycoprotein inhibition in the rat blood-brain barrier can be studied with PET.

Active efflux transporters in the blood-brain barrier lower the brain concentrations of many drug molecules and endogenous substances and thus affect their central action. The objective of this investigation was to study the dynamics of the entire inhibition process of the efflux transporter P-glycoprotein (P-gp), using positron emission tomography (PET). The P-gp marker [(11)C]verapamil was administered to anesthetized rats as an i.v. bolus dose followed by graded infusions via a computerized pump system to obtain a steady-state concentration of [(11)C]verapamil in brain. The P-gp modulator cyclosporin A (CsA) (3, 10 and 25 mg/kg) was administered as a short bolus injection 30 min after the start of the [(11)C]verapamil infusion. The CsA pharmacokinetics was studied in whole blood in a parallel group of rats. The CsA blood concentrations were used as input to model P-gp inhibition. The inhibition of P-gp was observed as a rapid increase in brain concentrations of [(11)C]verapamil, with a maximum after 5, 7.5 and 17.5 min for the respective doses. The respective increases in maximal [(11)C]verapamil concentrations were 1.5, 2.5 and 4 times the baseline concentration. A model in which CsA inhibited P-gp by decreasing the transport of [(11)C]verapamil out from the brain resulted in the best fit. Our data suggest that it is not the CsA concentration in blood, but rather the CsA concentration in an effect compartment, probably the endothelial cells of the blood-brain barrier that is responsible for the inhibition of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Two-year follow-up of amyloid deposition in patients with Alzheimer's disease.

Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.

Aged↗

PubMed2006

PET imaging of cortical 11C-nicotine binding correlates with the cognitive function of attention in Alzheimer's disease.

RATIONALE: Patients suffering from Alzheimer's disease (AD) experience a marked reduction in cortical nicotinic acetylcholine receptors (nAChRs). In particular, selective loss of the alpha4beta2 nAChR subtype was observed in postmortem AD brain tissue. The alpha4 and alpha7 nAChR subunits were suggested to play an important role in cognitive function. Positron emission tomography (PET) has so far been used to visualize neuronal nAChRs in vivo by 11C-nicotine binding. OBJECTIVES: To investigate the relationship between measures of cognitive function and in vivo 11C-nicotine binding in mild AD brain as assessed by PET. MATERIALS AND METHODS: Twenty-seven patients with mild AD were recruited in this study. A dual tracer model with administration of 15O-water for regional cerebral blood flow and (S)(-)11C-nicotine was used to assess nicotine binding sites in the brain by PET. Cognitive function was assessed using neuropsychological tests of global cognition, episodic memory, attention, and visuospatial ability. RESULTS: Mean cortical 11C-nicotine binding significantly correlated with the results of attention tests [Digit Symbol test (r = -0.44 and p = 0.02) and Trail Making Test A (TMT-A) (r = 0.42 and p = 0.03)]. No significant correlation was observed between 11C-nicotine binding and the results of tests of episodic memory or visuospatial ability. Regional analysis showed that 11C-nicotine binding in the frontal and parietal cortex, which are the main areas for attention, correlated significantly with the Digit Symbol test and TMT-A results. CONCLUSION: Cortical nicotinic receptors in vivo in mild AD patients are robustly associated with the cognitive function of attention.

Aged↗

PubMed2006

Validation studies on the 5-hydroxy-L-[beta-11C]-tryptophan/PET method for probing the decarboxylase step in serotonin synthesis.

The two-tissue compartment model, including irreversible trapping in the second compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[beta-(11)C]-tryptophan ([(11)C]HTP), a radioligand used in positron emission tomography (PET) for probing the second enzymatic step in the biosynthesis of serotonin. In this study, we examined the capacity of the model to track pharmacological changes in this biological process. We also investigated the potential loss of [(11)C]HTP-derived radioactivity during a PET study, since loss should be negligible not to alter quantification. Six rhesus monkeys were investigated using bolus [(11)C]HTP/PET methodology before and after pharmacological intervention. The second enzymatic step in serotonin synthesis was inhibited using the aromatic L-amino acid decarboxylase inhibitor NSD1015 (10 mg/kg). The extent of [(11)C]-derived radioactivity loss from the brain was studied by inhibition of the enzyme responsible for formation of the tissue metabolite, monoamine oxidase A, using clorgyline (2 mg/kg). After NSD1015, the uptake of [(11)C]HTP-derived radioactivity was increased in all the investigated brain regions, while the parameter used to reflect decarboxylase activity, the net accumulation rate constant (K(acc)), was decreased by 37% in the striatum, compared with baseline. Pretreatment with clorgyline did not change the brain uptake of [(11)C]HTP-derived radioactivity or K(acc). This study demonstrates that the 2TCM for [(11)C]HTP/PET is able to detect changes occurring during alteration of the biological process (i.e., the conversion of HTP to serotonin). Elimination of the radiotracer metabolite [(11)C]HIAA from the brain may be considered negligible if the PET study is limited to 60 min.

5-Hydroxytryptophan↗

PubMed2006

Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole.

Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [(11)C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K(d) of [(11)C]vorozole binding to aromatase in MA was determined to be 0.60+/-0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [(11)C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

Animals↗

PubMed2006

Multicellular tumour spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring.

BACKGROUND: In order to explore a pre-clinical method to evaluate if [18F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS) without and with treatment with five routinely used chemotherapy agents in breast cancer. METHODS: The response to each anticancer treatment was evaluated by measurement of the [18F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment. RESULTS: The effect of Paclitaxel and Docetaxel on [18F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease) than in MCF-7 (up to 25% decrease). Doxorubicin reduced the [18F]FDG uptake per viable volume more noticeable in MCF-7 (25%) than in BT474 MTSs. Tamoxifen reduced the [18F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 microM. No effect of Imatinib was observed. CONCLUSION: MTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur.The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response. In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs.

Journal Article↗

PubMed2006

Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria.

The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.

5-Hydroxytryptophan↗

PubMed2006

[11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings.

CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.

Adrenal Cortex Neoplasms↗

PubMed2006

Blood-brain barrier penetration of zolmitriptan--modelling of positron emission tomography data.

Positron emission tomography (PET) with the drug radiolabelled allows a direct measurement of brain or other organ kinetics, information which can be essential in drug development. Usually, however, a PET-tracer is administered intravenously (i.v.), whereas the therapeutic drug is mostly given orally or by a different route to the PET-tracer. In such cases, a recalculation is needed to make the PET data representative for the alternative administration route. To investigate the blood-brain barrier penetration of a drug (zolmitriptan) using dynamic PET and by PK modelling quantify the brain concentration of the drug after the nasal administration of a therapeutic dose. [11C]Zolmitriptan at tracer dose was administered as a short i.v. infusion and the brain tissue and venous blood kinetics of [11C]zolmitriptan was measured by PET in 7 healthy volunteers. One PET study was performed before and one 30 min after the administration of 5 mg zolmitriptan as nasal spray. At each of the instances, the brain radioactivity concentration after subtraction of the vascular component was determined up to 90 min after administration and compared to venous plasma radioactivity concentration after correction for radiolabelled metabolites. Convolution methods were used to describe the relationship between arterial and venous tracer concentrations, respectively between brain and arterial tracer concentration. Finally, the impulse response functions derived from the PET studies were applied on plasma PK data to estimate the brain zolmitriptan concentration after a nasal administration of a therapeutic dose. The studies shows that the PET data on brain kinetics could well be described as the convolution of venous tracer kinetics with an impulse response including terms for arterial-to-venous plasma and arterial-to-brain impulse responses. Application of the PET derived impulse responses on the plasma PK from nasal administration demonstrated that brain PK of zolmitriptan increased with time, achieving about 0.5 mg/ml at 30 min and close to a maximum of 1.5 mg/ml after 2 hr. A significant brain concentration was observed already after 5 min. The data support the notation of a rapid brain availability of zolmitriptan after nasal administration.

Blood-Brain Barrier↗

PubMed2006

Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults.

Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti-obesity drug target. We tested the hypothesis that blockade of the NPY5R will lead to weight loss in humans using MK-0557, a potent, highly selective, orally active NPY5R antagonist. The initial series of experiments reported herein, including a multiple-dose positron-emission tomography study and a 12 week proof-of concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The hypothesis was then tested in a 52 week, multicenter, randomized, double-blind, placebo-controlled trial involving 1661 overweight and obese patients. Although statistically significant at 52 weeks, the magnitude of induced weight loss was not clinically meaningful. These observations provide the first clinical insight into the human NPY-energy homeostatic pathway and suggest that solely targeting the NPY5R in future drug development programs is unlikely to produce therapeutic efficacy.

Administration, Oral↗

PubMed2006

The central circulation in congestive heart failure non-invasively evaluated with dynamic positron emission tomography.

BACKGROUND: Positron emission tomography (PET) with [15O]-H2O-PET (WAT-PET) or [11C]-acetate (AC-PET) quantifies myocardial perfusion and oxidative metabolism, but routine clinical use is hampered by the need for additional investigations to assess cardiac performance. OBJECTIVE: To apply classical tracer kinetics to dynamic PET could provide important haemodynamic parameters. METHODS: First-pass PET data were used with indicator dilution techniques to measure stroke volume index (SVI). Early pulmonary retention of [11C]-acetate was converted to standard uptake values (SUV) (Lung(AC-SUV)). Regional lung water (rLW) content was computed from the WAT-PET scan at equilibrium. PET was compared with radionuclide angiography and echocardiography in patients with ischaemic cardiomyopathy with New York Heart Association class II (n = 10) or III (n = 18) congestive heart failure. Elderly male volunteers without heart disease (n = 11) underwent AC-PET as controls. RESULTS: SVI with both tracers correlated in patients (r = 0.91, P<0.001, estimated standard error = 4 ml m(-2)) and with left ventricular ejection fraction (both tracers r>0.6, P<0.001). SVI was significantly different between all groups (ANOVA: P<0.001). Lung(AC-SUV) correlated with rLW (r = 0.78, P<0.001) and both were elevated in severe heart failure (P<0.05 for both). Elevated Lung(AC-SUV) was associated with a restrictive left ventricular (LV) filling pattern by Doppler echocardiography. CONCLUSION: Dynamic PET with first-pass analysis and tracers of myocardial perfusion enables quantification of the haemodynamic consequences of LV systolic and diastolic dysfunctions in ischaemic cardiomyopathy and could be useful in the evaluation of the central circulation in heart failure.

Acetates↗

PubMed2005

A new, fast and semi-automated size determination method (SASDM) for studying multicellular tumor spheroids.

BACKGROUND: Considering the width and importance of using Multicellular Tumor Spheroids (MTS) in oncology research, size determination of MTSs by an accurate and fast method is essential. In the present study an effective, fast and semi-automated method, SASDM, was developed to determinate the size of MTSs. The method was applied and tested in MTSs of three different cell-lines. Frozen section autoradiography and Hemotoxylin Eosin (H&E) staining was used for further confirmation. RESULTS: SASDM was shown to be effective, user-friendly, and time efficient, and to be more precise than the traditional methods and it was applicable for MTSs of different cell-lines. Furthermore, the results of image analysis showed high correspondence to the results of autoradiography and staining. CONCLUSION: The combination of assessment of metabolic condition and image analysis in MTSs provides a good model to evaluate the effect of various anti-cancer treatments.

Journal Article↗

PubMed2005

Photoinitiated free radical carbonylation enhanced by photosensitizers.

[reaction: see text] The enhancing effect of several photosensitizers in photoinitiated radical carbonylation is demonstrated and applied to accelerate the synthesis of compounds labeled with short-lived 11C. With the sensitizers, the synthesis of [carbonyl-11C]esters and acids from alkyl iodides, [11C]carbon monoxide, alcohols, and water provided up to 75-85% decay-corrected radiochemical yields in 6-min reactions under mild conditions. Acetone was used as a sensitizer in preparing 13C-substituted 1,10-decanedicarboxylic acid from (13C)carbon monoxide.

Journal Article↗