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ABSTRACT: Unilateral destruction of the substantia nigra by local application of 6-hydroxydopamine (6-OHDA) serves as an animal model for Parkinson's disease. In this study, the changes in neostriatal dopamine D(2) receptor density were investigated with a small animal positron emission tomograph (PET) before and after 6-OHDA lesion. PET scans were performed in 14 rats after injection of the D(2) receptor radioligand [(18)F] N-methylbenperidol. After the first scan (day 0), nigrostriatal pathways were lesioned by unilateral injections of 6-OHDA. Further PET scans were performed on days 2 and 14 post-lesion. For both striata, B(max) values were determined from saturation binding curves with non-linear regression analysis. In the striatum ipsilateral to the lesion, B(max) initially amounted to 19.3+/-1. 9 fmol/mg (mean+/-SD) and increased to 19.7+/-2.2 and 29.9+/-5.7 fmol/mg on days 2 and 14 post-lesion, respectively. Contralateral B(max) values increased from 19.2+/-2 fmol/mg prior to the lesion to 21.2+/-2.9 and 28.6+/-5.7 fmol/mg on days 2 and 14, respectively. On day 14, the ipsilateral saturation binding curve differed from the ipsilateral pre-lesion curve (P=0.04; F test). When the contralateral pre-lesion saturation binding curve was compared with the contralateral post-lesion curve on day 14, a P value of 0.08 was obtained. This first serial in vivo imaging study of 6-OHDA-lesioned rats showed a time-dependent increase in striatal D(2) receptor density on both sides, the increase being more pronounced ipsilateral to the lesion. This result implies that compensatory mechanisms in the intact hemisphere contribute to regenerative processes following nigrostriatal dopaminergic denervation. Overall, our findings show the feasibility of repetitive in vivo studies of striatal receptor density with a small animal tomograph. Moreover, the applied in vivo saturation binding technique provides a versatile method for the quantification of time-dependent changes in the concentration of receptor binding sites.
European journal of nuclear medicine and molecular imaging 04/2003; 30(3):390-5. · 4.99 Impact Factor
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ABSTRACT: We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.
Cognitive Brain Research 03/2003; 15(3):241-9. · 3.77 Impact Factor
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Rolf Larisch,
Ansgar Klimke,
Kurt Hamacher,
Uwe Henning,
Sorour Estalji,
Thomas Hohlfeld,
Henning Vosberg,
Marco Tosch,
Wolfgang Gaebel,
Heinz H Coenen, Hans Wilhelm Müller-Gärtner
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ABSTRACT: The feasibility of in vivo serotonin 5HT(2) receptor binding measurement using [18F]altanserin as a radioligand has been well established. In this study, the postsynaptic receptor binding potential of this ligand was examined as a possible indicator of synaptic serotonin content after pharmacological challenge. Studies were performed in 11 subjects with a history of recurrent major depression. Six of them received serotonergic antidepressive treatment at the time of the experiment, the other five patients were untreated. Two PET measurements were carried out in each subject within 2 or 3 days. Before one of the measurements, 25 mg of the serotonin re-uptake inhibitor clomipramine were given intravenously, the other measurement was done without pharmacological challenge. The data were analyzed using non-linear least-square regression and Logan's graphical method. In the whole group of subjects, binding potential and distribution volume of altanserin decreased following clomipramine challenge. The decrease was between 14 (P=0.03) and 23% (P=0.004). This effect was mainly seen in subjects not on antidepressive medication. Clomipramine challenge probably increased the synaptic serotonin level, which competed with altanserin leading to the lowered binding potential. The paradigm might, thus, be useful to estimate serotonin release in vivo. Pretreatment with serotonergic antidepressants reduces the effect of clomipramine.
Behavioural Brain Research 03/2003; 139(1-2):21-9. · 3.42 Impact Factor
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ABSTRACT: Verbal working memory has been attributed to a left-dominant neuronal network, including parietal, temporal and prefrontal cortical areas. The current study was designed to evaluate the contribution of these brain regions to verbal working memory processes and to assess possible hemispheric asymmetry. The effect of repetitive transcranial stimulation (rTMS) on performance in a verbal working memory task both during, and after an rTMS train (110% of individual motor threshold, 4 Hz) over nine different scalp locations was studied [bilateral middle frontal gyrus (MFG), bilateral supramarginal gyrus (SMG), bilateral inferior parietal cortex (IP) and three different midline control sites]. Significant performance deterioration was observed during rTMS over the left and right MFG and left and right IP. There was no consistent interference effect across subjects over the left or right SMG and the three different midline control sites. The interference effect with the given stimulation parameters did not last beyond the rTMS train itself. The data provide evidence for a symmetrical, bilateral parieto-frontal verbal working memory network. The data are discussed with respect to the competing ideas of a parieto-frontal central executive network vs. a network that processes the inherent semantic and object features of the visually presented verbal stimuli in parallel.
European Journal of Neuroscience 11/2002; 16(8):1627-32. · 3.63 Impact Factor
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Journal of Hepatology 11/2002; 37(4):539. · 9.26 Impact Factor
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ABSTRACT: The aim of this retrospective study was to investigate the value of positron emission tomography (PET) with 2-18fluor-2-deoxy-glucose (FDG) in the follow-up of Hürthle cell thyroid cancer (HTC), a rare variant of thyroid malignancies. FDG-PET studies were performed in 17 patients with HTC. In subgroup A (n = 13) PET was initiated because of an elevated thyroglobulin (Tg) level whereas in subgroup B (n = 4) the study was performed to evaluate suspect findings of morphologic imaging while Tg remained undetectable. Pathologically increased FDG uptake was found in all patients of subgroup A. In 10 studies, PET results were proven as true-positive either by surgery or by morphologic imaging. One study was false-positive. Final evaluation was not possible in two cases. In subgroup B, PET was true-negative in three and false-positive in one patient. For the detection of recurrent HTC by means of FDG-PET a meta-analysis including data of a multicenter study revealed an overall sensitivity of 92%, a specificity of 80%, a positive predictive value of 92%, and a negative predictive value of 80% while the accuracy was 89%. This study supports the efficiency of FDG-PET in the follow-up of HTC.
Thyroid 03/2002; 12(2):155-61. · 4.79 Impact Factor
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ABSTRACT: [90Y]DOTA-dPhe1-Tyr3-octreotide ([90Y]-SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order
to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [86Y]DOTA-dPhe1-Tyr3-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [86Y]DOTA-dPhe1-Tyr3-octreotide was administered at two different peptide concentrations, namely 2 and 100µg peptide per m2 body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [86Y]DOTA-dPhe1-Tyr3-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in l-lysine in order to lower the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded to measure the
uptake kinetics for kidneys, liver, lung and bone. The individual absolute uptake kinetics were used to calculate the radiation
doses for [90Y]DOTA-dPhe1-Tyr3-octreotide according to the MIRD recommendations extrapolated to a 70-kg human. The highest radiation dose was received by
the kidneys, with 2.1–3.3mGy per MBq [90Y]DOTA-dPhe1-Tyr3-octreotide injected. For the 100µg/m2 SMT487 protocol with amino acid co-infusion this dose was about 20%–40% lower than for the other two treatment protocols.
The liver and the red bone marrow received doses ranging from 0.32 to 0.53mGy and 0.03 to 0.07mGy per MBq [90Y]DOTA-dPhe1-Tyr3-octreotide, respectively. The average effective dose equivalent amounted to 0.23–0.32mSv/MBq. The comparatively low estimated
radiation doses to normal organs support the initiation of clinical phase I trials with [90Y]DOTA-dPhe1-Tyr3-octreotide in patients with somatostatin receptor-expressing tumours.
European journal of nuclear medicine and molecular imaging 03/1999; 26(4):358-366. · 4.99 Impact Factor
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ABSTRACT: The final publication is available at www.springerlink.com [[sup 90]Y]DOTA-DPhe[sup 1]-Tyr[sup 3]-octreotide ([[sup 90]Y]SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [[sup 86]Y]DOTA-DPhe[sup 1]-Tyr[sup 3]-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [[sup 86]Y]DOTADPhe[sup 1]-Tyr[sup 3]-octreotide was administered at two different peptide concentrations, namely 2 and 100 micro g peptide per m2 body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [[sup 86]Y]DOTA-DPhe[sup 1]-Tyr[sup 3]-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in L-lysine in order to lower the renal uptake of radioyttrium...
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ABSTRACT: Copyright: Elsevier The publication is available at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0G-3WG32FX-8&_user=106421&_coverDate=05%2F21%2F1999&_rdoc=8&_fmt=high&_orig=browse&_srch=doc-info%28%23toc%234862%231999%23997329998%2396221%23FLA%23display%23Volume%29&_cdi=4862&_sort=d&_docanchor=&_ct=19&_acct=C000007358&_version=1&_urlVersion=0&_userid=106421&md5=814b97188a962b77ecf756d8eec50b49 The present study addresses the effect of motivation on cerebral activity using functional magnetic resonance imaging. Five healthy volunteers performed a dichotic listening task in two sets of three trials during which high or low levels of achievement motivation were introduced. They were told that the first set would be used for calculation of intellectual capacity (high achievement motivation) and the second set for scanner calibration (neutral motivation). In three volunteers, high compared with neutral motivation produced activation in the right prefrontal cortex and the dorsal cingulate. We conclude that motivational effects may lead to significant activations and should be controlled in future cognitive imaging studies. We present preliminary evidence that right prefrontal and dorsal cingulate regions might be involved in motivational processes.
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ABSTRACT: Competition between endogenous dopamine and a radioligand for postsynaptic dopamine D2 receptor binding was examined in two groups of eight subjects each who had to read or write off a text, respectively, and in a control group. Single photon emission computed tomography (SPECT) and the ligand [123I]iodobenzamide (IBZM) were used for in vivo imaging. Subjects commenced reading or writing immediately before IBZM injection and continued for 30 min thereafter. SPECT images were acquired 60 min later. Striatum-to-parietal-cortex IBZM uptake ratios were lower in subjects who wrote off the text than in controls indicating competition of IBZM and dopamine. There was no difference between subjects who read the text and controls. Thus, dopamine release occurs as a consequence of the motoric activity involved in writing rather than of cognitive functions necessary for reading the text.
Neuroscience Letters.
