ORCID Profile
0000-0002-0945-0724
Current Organisation
University Medical Center Hamburg-Eppendorf
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Publisher: Wiley
Date: 14-07-2015
DOI: 10.1002/SYN.21838
Abstract: Aim of this study was to quantify the binding of [(123) I]FP-CIT in striatum of healthy tree shrews. [(123) I]FP-CIT is widely used in clinical SPECT imaging to reveal nigrostriatal degeneration in aid of the diagnosis of clinically uncertain parkinsonian syndromes. Despite its wide clinical use, the saturation binding parameters of [(123) I]FP-CIT for the dopamine transporter (DAT) have not yet been determined in any mammalian brain. Tree shrews are genetically and neuroanatomically more similar to humans than are rodents and might therefore be a valuable animal model for research of neurological disorders involving brain dopamine. Quantitative in vitro autoradiography with [(123) I]FP-CIT was performed with brains of healthy tree shrews and, for comparison, brains of healthy rats. Dopamine D2/3 receptor autoradiography with [(3) H]raclopride was also performed. Saturation analysis revealed high specificity of [(123) I]FP-CIT for DAT in the striatum with considerably higher affinity in tree shrews than in rats (KD = 10.3 versus 36.4 nM). The density of DAT binding sites also was higher in tree shrews than in rats (Bmax = 2499 versus 1495 pmol/g wet weight (ww)). [(3) H]raclopride revealed D2/3 receptors in the tree shrew striatum with about the same density as in rats (Bmax = 78.4 versus 84.1 pmol/g ww), but with slightly lower affinity in tree shrews (KD = 1.27 versus 0.59 nM). The higher affinity in combination with the higher abundance of DAT binding sites compared to rat striatum predicts substantially higher binding of [(123) I]FP-CIT in SPECT studies of living tree shrews.
Publisher: Georg Thieme Verlag KG
Date: 05-2014
DOI: 10.3413/NUKMED-0588-13-05
Abstract: Quantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. Aim: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. Patients, methods: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21 Siemens Biograph 16 PET/CT: n = 16 Philips Gemini-TF PET/CT: n = 19). Urine s les were collected immediately after scan. Activity concentration in the s les was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine s le) activity concentration ratio was determined. Results: Activity concentration in the bladder (PET) was systematically lower than in the urine s les (well The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. Conclusions: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine s les with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.
Publisher: Springer Science and Business Media LLC
Date: 19-06-2012
DOI: 10.1007/S00259-012-2162-4
Abstract: Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown. In a group of 16 healthy participants aged 22-61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K (in) (app) millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ. Cognitive speed was associated with the magnitude of K (in) (app) in the prefrontal cortex (p < 0.0005). Both cognitive speed (p = 0.003) and FDOPA K (in) (app) (p < 0.0005) declined with age, both in a standard voxel-wise analysis and in a volume-of-interest analysis with partial volume correction, and the correlation between cognitive speed and K (in) (app) remained significant beyond the effects of age (p = 0.047). MR-based segmentation revealed that these age-related declines were not attributable to age-related alterations in grey matter density. Our findings indicate that age-related changes in the capacity of the prefrontal cortex to synthesize catecholamines, irrespective of cortical atrophy, may underlie age-related decline in cognitive speed.
Publisher: Wiley
Date: 26-12-2014
DOI: 10.1111/EJN.12802
Publisher: Wiley
Date: 17-02-2012
DOI: 10.1002/HBM.22000
Abstract: Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a s le of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subs le of 17 subjects also with positron emission tomography using 6‐[ 18 F]fluoro‐ L ‐DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA K ). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that in idual differences in the capacity for flexible problem solving relate to ventral striatal activation during reward‐related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
No related grants have been discovered for Ralph Buchert.