Biomedical subjects

Pál Mikecz

Publications and source records attributed to Pál Mikecz.

8 recordsLinked to original sources

PubMed2006

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

OBJECTIVE: Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory "oddball" paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. METHOD: Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [15O]-butanol activity changes in the PET camera was recorded. RESULTS AND DISCUSSION: Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area - BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. CONCLUSIONS: The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area - and consequently a larger variety of neuronal networks--is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.

Acoustic Stimulation↗

PubMed2003

In vivo and in vitro multitracer analyses of P-glycoprotein expression-related multidrug resistance.

P-glycoprotein (Pgp) is an ABC (ATP binding cassette) transporter that is often overexpressed in tumours, contributing significantly to their multidrug resistance. In this study, we explored whether the radiotracers used in tumour diagnostics can be used for in vivo visualisation of Pgp-related multidrug resistance. We also examined the effects of different Pgp modulators on the accumulation of these radioligands in tumours with or without Pgp expression. In a SCID BC-17 mouse model, cells of the drug-sensitive KB-3-1 (MDR(-)) and the KB-V1 Pgp-expressing (MDR(+)) human epidermoid carcinoma cell lines were inoculated to yield tumours in opposite flanks. For in vivo scintigraphic (biodistribution) and positron emission tomography (PET) examinations, the mice were injected with technetium-99m hexakis-2-methoxybutylisonitrile ((99m)Tc-MIBI), carbon-11 labelled methionine and fluorine-18 fluoro-2-deoxy- d-glucose ((18)FDG). For validation, in vitro cell studies with (99m)Tc-MIBI,( 99m)Tc-tetrofosmin, [(11)C]methionine and (18)FDG were carried out using a gamma counter. The expression and function of the MDR product were proved by immunohistochemistry and spectrofluorimetry. (99m)Tc-MIBI uptake was significantly lower in KB-V1 cells as compared with KB-3-1-derived tumours in vivo (Pgp(+)/Pgp(-) =0.61+/-0.13; P<0.01) and cells in vitro (Pgp(+)/Pgp(-) =0.08+/-0.01; P<0.001).()Cyclosporin A reversed (99m)Tc-MIBI uptake in the Pgp+ cells, while verapamil failed to modify it. (18)FDG uptake was significantly higher in KB-V1 tumours (Pgp(+)/Pgp(-) =1.36+/-0.05; P<0.01) and cells (Pgp(+)/Pgp(- )=1.52+/-0.12; P<0.001). Whereas cyclosporin A eliminated the difference between FDG uptake in MDR(+) and MDR(-) cell lines, verapamil significantly increased it. When the animals were treated with verapamil, the ratio of (99m)Tc-MIBI uptake in the MDR(+) tumours to that in the MDR(-) tumours decreased to 0.38+/-0.05 ( P<0.01), while the ratio of (18)FDG uptake increased to 2.1+/-0.3 ( P<0.001). There were no significant differences in the [(11)C]methionine uptake in the MDR(+) and MDR(-) tumours and cell lines, nor was [(11)C]methionine accumulation modified by cyclosporin A. Parallel administration of (18)FDG and (99m)Tc-MIBI combined with verapamil treatment seems to be a good candidate as a non-invasive marker for the diagnosis of MDR-related Pgp expression in tumours.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

[Synthesis of radiopharmaceuticals for PET investigations].

The PET radiopharmaceuticals are prepared on the spot in most cases due to the short lifetime of the isotopes used. The first step of this process is the isotope production by small cyclotrons. The synthons made from the isotopes react with the precursor of the given radiopharmaceutical. The target compound selected from the reaction mixture is ready for injection after purification, formulation and sterile filtration. In addition to [18F]-FDG, [11C]-methionine and [15O]-butanol routinely used for diagnostic purposes in the PET Centre of the University of Debrecen, a number of other radiopharmaceuticals are synthesized for use in research from time to time.

Hungary↗

PubMed2002

[Comparative analysis of quantitative evaluation methods for FDG-PET scans].

The comparative analysis of two kinetic methods most frequently applied for the quantization of the results of FDG-PET brain scans was performed applying PET investigations and computer simulations. The analysis of the measured data and computer simulation demonstrated that the applicability of the results of SUV-methods to estimate glucose metabolic rates (GMR) as calculated by the Phelps-method (the most advanced method ) depended on the selected cerebral region. The distorted estimation was explained by the fact that the simpler models neglect dephosphorylation of the FDG-6P, and they also disregard the contribution of the intravascular activity to the tissue radioactivity. The simulations revealed the lack of a general and close positive correlation between SUV and GMR data; under special circumstances they might even change in an inverse manner.

Computer Simulation↗

PubMed2002

[Detection of recurrent head and neck cancer with positron emission tomography].

Differentiation between recurrence and post-therapeutic lesions in patients with previously treated head and neck cancer can be a real diagnostic problem. The authors discuss the role of positron emission tomography in restaging of this disease by a retrospective analysis based on 20 scans of 17 patients. PET findings were correct in identifying tumors in 85% of patients (11/13) in the group of positive PET results. All negative PET findings (4/4) were also correct during the follow-up. PET results were validated in 88% (15/17) of the patients. In one case silent distant metastases were also detected. PET is a reliable method in restaging previously treated head and neck cancer patients as it can differentiate post-therapeutic changes from tumor relapse.

Adult↗

PubMed2002

[The role of PET scan in the investigation of epileptic functional disorders].

Systematic research is needed to evaluate the exact role of pathological factors in the determination of the extension of the hypometabolic area in partial epileptic patients. Together with structural damage, previous seizures, deafferentation and inhibitory mechanisms may contribute to the functional disorders. Benzodiazepine receptor studies showed that the density and binding ability of these receptors decreased in the area of epileptic functional disorder. Circumscribed hypermetabolism may appear during epileptic seizures or even more electrical discharges. The authors' PET studies aimed at presurgical evaluation showed that bilateral temporal hypometabolism occurred more frequently with right-sided seizure start. FDG-PET supported the localization of the pacemaker area both in temporal lobe epilepsies and in extratemporal epilepsies. This method proved instrumental in delineating the extension of the background pathology, too. The authors also demonstrated the strength of PET brain activation in mapping the hemispheric distribution of speech functions required in the planning of surgical interventions. The role of hippocampal sclerosis in temporal lobe hypometabolism was investigated and a short account is given of the observations relating to the relationship of hypermetabolism due to subclinical epileptic discharges and cognitive deficit symptoms.

Brain↗

PubMed2002

[The [18F]-FNECA serves as a suitable radioligand for PET investigation of purinergic receptor expression].

The well known and widely used P1 adenosine agonist, 5'-N-ethyl-carboxamidoadenosine (NECA), was labelled with 18F isotope for the in vivo PET investigation of A1, A2 and A3 adenosine receptor expression. The precursor 2-[18F]fluoroethylamine was reacted with 2',3'-O-isopropylideneadenosine-5'-uronic acid. Specific activity of the [18F]-FNECA was (2.3 +/- 1.1) TBq/mmol (60 Ci/mmol). Dynamic PET measurements were carried out in rabbits to study the in vivo kinetics of the receptor saturation with the labelled ligand. The time dependent accumulation was followed up in the heart, lungs, liver, brain and testis. The radiotracer uptake was rapid and reached its maximum in less than two minutes in the heart and testes after v. injection of the radiopharmaceutical, while it took about 6 minutes in the brain, lungs and liver. High [18F]-FNECA accumulation was detected in the intestines, too. The specific binding of the [18F]-FNECA was tested in competition experiments in brain and heart sections using autoradiographic technique. The outlined synthesis provided sufficient amounts of [18F]-FNECA to map adenosine receptor expression under physiological conditions.

Adenosine-5'-(N-ethylcarboxamide)↗

PubMed2002

[Effect of flumazenil on the regional cerebral blood flow measured by [15O]-butanol PET scan and transcranial Doppler ultrasonography].

The authors investigated the role of the cBZD/GABA-A receptor-complex in the regulation of rCBF by simultaneously applying [15O]-butanol-PET and TCD in therapy-resistant TLE patients. It is known that the density of the cBZD/GABA-A-receptors is reduced in the epileptogenic area of the temporal lobe, but there are no data available about the impact of this phenomenon on rCBF. FMZ is a well-known BZD-receptor antagonist which can be used to inhibit the effect mediated by cBZD/GABA-A-receptors, offering a way to study the contribution of these receptors in the determination of rCBF. The authors examined the possible correlation between the rCBF values obtained by PET and the blood flow speed readings measured by TCD in MCAs. The results show that FMZ does not cause any change in rCBF on the side of the epileptogenic focus but it significantly raises rCBF (p < 0.001) in the intact brain tissue on the other side. The TCD measurements showed no significant differences between the blood flow in the MCAs supplying the affected and the contralateral lobe.

Adult↗