Influence of anesthesia on brain distribution of [11C]methamphetamine in monkeys in positron emission tomography (PET) study

Mizugaki, Michinao; Nakagawa, Naoto; Nakamura, Hitoshi; Hishinuma, Takanori; Tomioka, Y.; Ishiwata, Shunji; Ido, Tatsuo; Iwata, Ren; Funaki, Y.; Itoh, Masatoshi; Higuchi, M.; Okamura, Nobuyuki; Fujiwara, Takehiko; Sato, Motonobu; Shindo, Katsuhiro; Yoshida, Sumiko

doi:10.1016/s0006-8993(01)02669-5

Cited by 6 publications

(5 citation statements)

References 6 publications

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“…This finding can be examined in future studies on human methamphetamine abusers. We also note that prior studies on monkeys found an influence of different types of anesthesia on methamphetamine kinetics (12); thus, future studies on humans should assess methamphetamine kinetics in the awakened state.…”

Section: Discussionmentioning

confidence: 82%

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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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Section: Discussionmentioning

confidence: 82%

“…Mizugaki et al reported differences in 11 C-methamphetamine uptake with different anesthetics (12), and though the authors did not specify the enantiomeric form, earlier studies in this same group studied methamphetamine sensitization using the active enantiomer, 11 C-d-methamphetamine (13).…”

mentioning

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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“…For example, biochemical studies measuring norepinephrine, epinephrine, and corticosterone levels have indicated that it may be difficult to adapt rats to daily episodes of immobilization stress, even after 2 weeks of daily exposure [3,4]. Furthermore, the use of even low doses of an anesthetic or neurosedative agents for stress relief in animals inside the scanner may confound meaningful interpretation of the results [5][6][7][8][9]. Ideally, functional neuroimaging of mammalian behaviors could occur in freely moving subjects, while presenting minimal interference with the subject's natural behavior.…”

Section: Introductionmentioning

confidence: 99%

Mapping brain function in freely moving subjects

Holschneider

Maarek

2004

Neuroscience & Biobehavioral Reviews

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Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject's natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease.

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“…It has been demonstrated in numerous instances that anesthesia can affect the behavior of PET tracers. − Therefore, an 85 min PET study was performed on a high resolution research tomograph (HRRT) with [ 18 F] 9 in an awake rhesus monkey to determine whether there is a difference between the behavior of [ 18 F] 9 in awake and anesthetized states (Figures and ). As shown in Figure , the uptake of [ 18 F] 9 is nearly equal in the putamen and caudate in each hemisphere of the awake rhesus monkey brain.…”

Section: In Vivo Nonhuman Primate Pet Imagingmentioning

confidence: 99%

“…Furthermore, the uptake in 64 It has been demonstrated in numerous instances that anesthesia can affect the behavior of PET tracers. [93][94][95][96][97][98] Therefore, an 85 min PET study was performed on a high resolution research tomograph (HRRT) with [ 18 F]9 in an awake rhesus monkey to determine whether there is a difference between the behavior of [ 18 F]9 in awake and anesthetized states (Figures 7 and 8).…”

Section: In Vivo Nonhuman Primate Pet Imagingmentioning

confidence: 99%

Synthesis, Fluorine-18 Radiolabeling, and Biological Evaluation of N-((E)-4-Fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-(4′-halophenyl)nortropanes: Candidate Radioligands for In Vivo Imaging of the Brain Dopamine Transporter with Positron Emission Tomography

Stehouwer¹,

Daniel²,

Chen³

et al. 2010

J. Med. Chem.

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The N-(E)-fluorobutenyl-3β-(para-halo-phenyl)nortropanes 9-12 were synthesized as ligands of the dopamine transporter (DAT) for use as 18F-labeled positron emission tomography (PET) imaging agents. In vitro competition binding assays demonstrated that compounds 9-12 have a high affinity for the DAT and are selective for the DAT compared to the serotonin and norepinephrine transporters. MicroPET imaging with [18F]9-[18F]11 in anesthetized cynomolgus monkeys showed high uptake in the putamen with lesser uptake in the caudate, but significant washout of the radiotracer was only observed for [18F]9. PET imaging with [18F]9 in an awake rhesus monkey showed high and nearly equal uptake in both the putamen and caudate with peak uptake achieved after 20 min followed by a leveling-off for about 10 min and then a steady washout and attainment of a quasi-equilibrium. During the time period 40-80 min post-injection of [18F]9 the ratio of uptake in the putamen and caudate vs. cerebellum uptake was ≥ 4.

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Influence of anesthesia on brain distribution of [11C]methamphetamine in monkeys in positron emission tomography (PET) study

Cited by 6 publications

References 6 publications

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

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

Mapping brain function in freely moving subjects

Synthesis, Fluorine-18 Radiolabeling, and Biological Evaluation of N-((E)-4-Fluorobut-2-en-1-yl)-2β-carbomethoxy-3β-(4′-halophenyl)nortropanes: Candidate Radioligands for In Vivo Imaging of the Brain Dopamine Transporter with Positron Emission Tomography

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