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Purpose: [C]DASB is currently the most frequently used highly selective radiotracer for visualization and quantification of central SERT. Its use, however, is hampered by the short half-life of C, the moderate cortical test-retest reliability, and the lack of quantifying endogenous serotonin. Labelling with F allows in principle longer acquisition times for kinetic analysis in brain tissue and may provide higher sensitivity. The aim of our study was to firstly use the new highly SERT-selective F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[F]FMe-McN5652) in humans and to evaluate its potential for SERT quantification. Methods: The PET data from five healthy volunteers (three men, two women, age 39 ± 10 years) coregistered with individual MRI scans were semiquantitatively assessed by volume-of-interest analysis using the software package PMOD. Rate constants and total distribution volumes ( V) were calculated using a two-tissue compartment model and arterial input function measurements were corrected for metabolite/plasma data. Standardized uptake region-to-cerebellum ratios as a measure of specific radiotracer accumulation were compared with those of a [C]DASB PET dataset from 21 healthy subjects (10 men, 11 women, age 38 ± 8 years). Results: The two-tissue compartment model provided adequate fits to the data. Estimates of total distribution volume ( V) demonstrated good identifiability based on the coefficients of variation (COV) for the volumes of interest in SERT-rich and cortical areas (COV V <10%). Compared with [C]DASB PET, there was a tendency to lower mean uptake values in (+)-[F]FMe-McN5652 PET; however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[F]FMe-McN5652 uptake corresponded well with the known SERT distribution in humans. Conclusion: The results showed that (+)-[F]FMe-McN5652 is also suitable for in vivo quantification of SERT with PET. Because of the long half-life of F, the widespread use within a satellite concept seems feasible. [ABSTRACT FROM AUTHOR]

Functional changes of nicotinic acetylcholine receptors (nAChR) are important during age-related neuronal degeneration. Recent studies demonstrate the applicability of the nAChR ligand 2-[18F]F-A-85380 for neuroimaging of patients with dementias. However, its binding kinetics demands a 7-h acquisition time limiting its practicality for clinical PET studies. Thus, the authors developed [18F]norchloro-fluoro-homoepibatidine ([18F]NCFHEB) for nAChR imaging. The kinetics of the two enantiomers of [18F]NCFHEB were compared with 2-[18F]F-A85380 in porcine brain to evaluate their potential for human neuroimaging. Twenty-four juvenile female pigs were studied with PET using [18F]NCFHEB. Nine animals received an additional i.v. injection (1 mg/kg) of the nAChR agonist A81418 before radiotracer administration followed by infusion (2 mg/kg/7h) thereafter. Several compartment models were applied for quantification. (−)- and (+)-[18F]NCFHEB showed a twofold to threefold higher brain uptake than 2-[18F]F-A-85380. All three radiotracers displayed spatially hetereogenous binding kinetics in regions with high, moderate, or low specific binding. The equilibrium of specific binding of (−)-[18F]NCFHEB was reached earlier than that of (+)-[18F]NCFHEB or 2-[18F]F-A85380. Continuous administration of the nAChR agonist A81418 inhibited the specific binding of (−)- and (+)-[18F]NCFHEB but not of 2-[18F]F-A85380. The peripheral metabolism of (+)-[18F]NCFHEB proceeded somewhat slower than that of the other radiotracers. Both enantiomers of [18F]NCFHEB are appropriate radiotracers for neuroimaging of nAChR in pigs. Their binding profile in vivo appears to be more selective than that of 2-[18F]F-A85380. (−)-[18F]NCFHEB offers a faster equilibrium of specific binding than 2-[18F]F-A85380. Synapse 62:205-218, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Wilson's disease (WD) is a copper deposition disorder which can result in a number of extrapyramidal motoric symptoms such as parkinsonism. Therefore, this study was carried out to investigate, for the first time, nigrostriatal dopaminergic function in WD in relation to different courses and severity of the disease. Using high-resolution single-photon emission tomography (SPET) after administration of 2ß-carbomethoxy-3ß-(4[[sup 123] I]iodophenyl)tropane ([[sup 123] I]ß-CIT), striatal dopamine transporters (DAT) were imaged in 43 WD patients and a control group of ten subjects. From the SPET images, specific [[sup 123] I]ß-CIT binding ratios were obtained for the caudate heads, putamina and entire corpus striatum. In addition, to evaluate a putative dissociation between the caudate and putaminal [[sup 123] I]ß-CIT binding ratios, the ratio between these binding ratios was calculated (CA/PU ratio). The SPET data were compared with clinical data on the course of the disease (CD), the severity of neurological symptoms and the degree of hepatic alteration. Whereas the specific regional [[sup 123] I]ß-CIT binding ratios in patients with asymptomatic/hepatic CD did not differ from those in the control group (e.g. striatal ratios: 13.4±3.0 vs 11.7±2.8), in patients with neurological CD the ratios were significantly reduced for all striatal substructures (P=0.003 after one-factor ANOVA). For the different subgroups a tendency was detected towards a stepwise decrease in the specific [[sup 123] I]ß-CIT binding ratios from pseudo-sclerosis CD (9.4±2.3), through pseudo-parkinsonian CD (9.1±2.1) to arrhythmic-hyperkinetic CD (8.5±1.6). However, these group differences reached significance only for the comparison with asymptomatic/hepatic CD (P=0.02). The CA/PU ratio was significantly higher in WD than in the control group (1.30±0.19 vs 1.11±0.08; P=0.003). Severity of neurological symptoms was signifi... [ABSTRACT FROM AUTHOR]

Context: Cognitive or depressive disorders are frequently noted in patients with Parkinson disease (PD) and may be related to altered signaling through alpha4beta2*-nicotinic acetylcholine receptors (alpha4beta2*-nAChRs)., Objective: To assess the availability of alpha4beta2*-nAChRs and their relationship to mild cognitive and mild depressive symptoms in vivo in patients with PD., Design: Crossover comparison between patients with PD and healthy volunteers (control group) using the alpha4beta2*-nAChR-specific radioligand 2-[(18)F]fluoro-3-(2[S]-2-azetidinylmethoxy)-pyridine (2-[(18)F]FA-85380) and positron emission tomography., Setting: Departments of Neurology and Nuclear Medicine, University of Leipzig, Leipzig, Germany., Participants: Twenty-two nonsmoking patients with PD and 9 nonsmoking healthy volunteers., Main Outcome Measures: Level of 2-[(18)F]FA-85380 binding potential (2-FA BP), a measure of alpha4beta2*-nAChR availability. The relationship between severity of cognitive symptoms as rated using the Mini-Mental State Examination and DemTect scale and the level of depressive symptoms as indicated using the Beck Depression Inventory, and 2-FA BP were assessed., Results: In patients with PD compared with healthy volunteers, there was widespread reduced 2-FA BP, especially in the midbrain, pons, anterior cingulate cortex, frontoparietal cortex, and cerebellum. In subgroups of patients with PD with possible depression, reduced 2-FA BP was most pronounced in the cingulate cortex and frontoparieto-occipital cortex, whereas in patients with PD with mild cognitive impairment, 2-FA BP was reduced in the midbrain, pons, and cerebellum. In patients with PD, the strongest associations between depressive symptoms and reduced 2-FA BP were noted in the anterior cingulate cortex, putamen, midbrain, and occipital cortex. In contrast, cognitive symptoms correlated only weakly with reduced 2-FA BP in the thalamus, midbrain, temporal cortex, hippocampus, and cerebellum., Conclusions: There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced alpha4beta2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.