6‐[<sup>18</sup>F]Fluoro‐A‐85380, a new PET tracer for the nicotinic acetylcholine receptor: Studies in the human brain and in vivo demonstration of specific binding in white matter

Ding, Yu; Fowler, Joanna S.; Logan, Jean; Wang, Gene Jack; Telang, Frank; Garza, Victor; Biegon, Anat; Pareto, Deborah; Rooney, William D.; Shea, Colleen; Alexoff, David; Volkow, Nora D.; Vocci, Frank

doi:10.1002/syn.20051

Cited by 91 publications

(63 citation statements)

References 35 publications

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“…Ligand-binding studies have revealed the presence of nicotinic receptors in the cortical white matter (Ding et al, 2004), though significant nicotinic binding has not been noted in the corpus callosum per se. Nevertheless, previous studies have revealed that nicotinic receptors are specifically involved in the regulation of oligodendrocyte development.…”

Section: Discussionmentioning

confidence: 99%

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

Paul

Grieve

Niaura

et al. 2008

Nicotine & Tobacco Res.

115

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Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure.

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Section: Discussionmentioning

confidence: 99%

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

Paul

Grieve

Niaura

et al. 2008

Nicotine & Tobacco Res.

115

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“…11 C-Nicotine is another example. There is no doubt that nicotine binds to nicotine receptors in the brain, as can be demonstrated by its pharmacologic activity and by observing the ability of unlabeled nicotine to displace a radiotracer with specificity for the nicotinic acetylcholine receptor (26). However, 11 C-nicotine cannot be blocked by unlabeled nicotine because it binds to many other nonspecific sites and the signal is lost in the noise.…”

Section: Discussionmentioning

confidence: 99%

PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and ( )-Cocaine

Fowler

Kroll

Ferrieri

et al. 2007

Journal of Nuclear Medicine

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The methamphetamine molecule has a chiral center and exists as 2 enantiomers, d-methamphetamine (the more active enantiomer) and l-methamphetamine (the less active enantiomer). d-Methamphetamine is associated with more intense stimulant effects and higher abuse liability. The objective of this study was to measure the pharmacokinetics of d-methamphetamine for comparison with both l-methamphetamine and (2)-cocaine in the baboon brain and peripheral organs and to assess the saturability and pharmacologic specificity of binding. Methods: d-and l-methamphetamine and (2)-cocaine were labeled with 11 C via alkylation of the norprecursors with 11 C-methyl iodide using literature methods. Six different baboons were studied in 11 PET sessions at which 2 radiotracer injections were administered 2-3 h apart to determine the distribution and kinetics of 11 C-d-methamphetamine in brain and peripheral organs. Saturability and pharmacologic specificity were assessed using pretreatment with d-methamphetamine, methylphenidate, and tetrabenazine. 11 C-d-Methamphetamine pharmacokinetics were compared with 11 C-l-methamphetamine and 11 C-(2)-cocaine in both brain and peripheral organs in the same animal. Results: 11 C-d-and l-methamphetamine both showed high uptake and widespread distribution in the brain. Pharmacokinetics did not differ between enantiomers, and the cerebellum peaked earlier and cleared more quickly than the striatum for both. 11 C-d-Methamphetamine distribution volume ratio was not substantially affected by pretreatment with methamphetamine, methylphenidate, or tetrabenazine. Both enantiomers showed rapid, high uptake and clearance in the heart and lungs and slower uptake and clearance in the liver and kidneys. A comparison of 11 C-d-methamphetamine and 11 C-(2)-cocaine showed that 11 C-d-methamphetamine peaked later in the brain than did 11 C-(2)-cocaine and cleared more slowly. The 2 drugs showed similar behavior in all peripheral organs examined except the kidneys and pancreas, which showed higher uptake for 11 C-d-methamphetamine. Conclusion: Brain pharmacokinetics did not differ between d-and l-methamphetamine and thus cannot account for the more intense stimulant effects of d-methamphetamine. Lack of pharmacologic blockade by methamphetamine indicates that the PET image represents nonspecific binding, though the fact that methamphetamine is both a transporter substrate and an inhibitor may also play a role. A comparison of 11 C-d-methamphetamine and 11 C-(2)-cocaine in the same animal showed that the slower clearance of methamphetamine is likely to contribute to its previously reported longer-lasting stimulant effects relative to those of (2)-cocaine. High kidney uptake of d-methamphetamine or its labeled metabolites may account for the reported renal toxicity of d-methamphetamine in humans.

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“…Consequently, the whole brain ratio results were the most conservative. Although white matter clearly accumulated the tracer, at least two studies suggest that the corpus callosum does not (Ding, et al, 2004, Staley, et al, 2005. While further work is required to confirm this, using callosum as a reference region would greatly simplify quantification of 5-IA uptake.…”

Section: Discussionmentioning

confidence: 99%

5-123I-A-85380 binding to the α4β2-nicotinic receptor in mild cognitive impairment

Terriere

Dempsey

Herrmann

et al. 2010

Neurobiology of Aging

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Treatments currently licensed for Alzheimer's dementia target cholinergic brain systems. In vivo nicotinic receptor binding may provide an early marker of illness and treatment suitability. In this pilot, we examined nine patients with amnestic mild cognitive impairment (MCI) and ten age and education matched healthy volunteers with high resolution SPECT and the nicotinic receptor ligand 123I-5-IA-85380. Uptake data were analysed using voxel-based techniques for group comparisons and regression analyses with cognitive impairment as covariates. MCI patients had discrete reductions in uptake in medial temporal cortex.Correlations with cognitive impairment were found in left temporo-parietal areas (Addenbrooke's Cognitive Examination) and bilateral temporo-limbic areas (Reye Auditory Verbal Learning Test), and right parahippocampal gyrus (Reye Complex Figure Test)

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6‐[¹⁸F]Fluoro‐A‐85380, a new PET tracer for the nicotinic acetylcholine receptor: Studies in the human brain and in vivo demonstration of specific binding in white matter

Cited by 91 publications

References 35 publications

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and ( )-Cocaine

5-123I-A-85380 binding to the α4β2-nicotinic receptor in mild cognitive impairment

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6‐[18F]Fluoro‐A‐85380, a new PET tracer for the nicotinic acetylcholine receptor: Studies in the human brain and in vivo demonstration of specific binding in white matter

Cited by 91 publications

References 35 publications

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: A diffusion tensor imaging study

PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and ( )-Cocaine

5-123I-A-85380 binding to the α4β2-nicotinic receptor in mild cognitive impairment

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6‐[¹⁸F]Fluoro‐A‐85380, a new PET tracer for the nicotinic acetylcholine receptor: Studies in the human brain and in vivo demonstration of specific binding in white matter