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Positron emission tomography as a tool for studying alcohol abuse.

ABSTRACT: Positron emission tomography (PET) is an imaging technology that measures the concentration, distribution, and pharmacokinetics of radiotracers-molecules that are labeled with short-lived positron-emitting variants of chemical elements naturally found in the body. These radioisotopes can be attached to compounds involved in normal brain function and then injected into the blood stream. The signals emitted by these radiotracers then are measured using specific detectors. PET is a highly sensitive method; it measures radioisotope concentrations in the nanomolar to picomolar range (10-9 to 10-12 M) . Therefore, the technique can be used to label compounds that are of pharmacological and physiological relevance. These radiotracers then can be used to probe neurochemical and metabolic processes at the relevant physiological concentrations without perturbing the system that is measured. To exert their effects on the brain, alcohol and other drugs (AODs) act on signaling molecules (i.e., neurotransmitters) in the brain as well as on the molecules on the surface of neurons (i.e., receptors) with which the neurotransmitters interact. Specific compounds that selectively bind to such receptors, to the molecules that transport neurotransmitters back into cells, and to the enzymes that are involved in the synthesis or metabolism of neurotransmitters can be labeled for use as PET radiotracers. As a result, PET can be used to assess the metabolic and neurochemical actions of AODs and to evaluate the consequences of chronic AOD use. Since its inception, PET has been used extensively to study the effects of AODs in human and nonhuman primates; however, the recent development of microPET technology has expanded its applications to research in rodents. In addition, increasing numbers of studies are using PET methodology to assess the involvement of genetic variations in individual genes (i.e., polymorphisms) in brain function and neurochemistry. The studies discussed are divided into those that assess the effects of alcohol on brain function (i.e., brain metabolism and cerebral blood flow) and those that assess the effects of alcohol on brain function (i.e., brain metabolism and cerebral blood flow) and those that assess its effects on neurochemistry.

SUBMITTER: Thanos PK

PROVIDER: S-EPMC3860484 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Positron emission tomography as a tool for studying alcohol abuse.

Thanos Panayotis K PK Wang Gene-Jack GJ Volkow Nora D ND

Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism 20080101 3

Positron emission tomography (PET) is an imaging technology that measures the concentration, distribution, and pharmacokinetics of radiotracers-molecules that are labeled with short-lived positron-emitting variants of chemical elements naturally found in the body. These radioisotopes can be attached to compounds involved in normal brain function and then injected into the blood stream. The signals emitted by these radiotracers then are measured using specific detectors. PET is a highly sensitive ...[more]

PMID: 23584865

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Project description:ImportanceThe recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies of Alzheimer disease (AD): amyloid-β plaques and tau neurofibrillary tangles.ObjectiveTo determine whether cerebrospinal fluid (CSF) and plasma p-tau biomarkers preferentially reflect cerebral β-amyloidosis or neurofibrillary tangle aggregation measured with positron emission tomography (PET).Design, setting, and participantsThis was a cross-sectional study of 2 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) study, with data collected between October 2017 and August 2021, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), with data collected between September 2015 and November 2019. TRIAD was a single-center study, and ADNI was a multicenter study. Two independent subsamples were derived from TRIAD. The first TRIAD subsample comprised individuals assessed with CSF p-tau (p-tau181, p-tau217, p-tau231, p-tau235), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. The second TRIAD subsample included individuals assessed with plasma p-tau (p-tau181, p-tau217, p-tau231), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. An independent cohort from ADNI comprised individuals assessed with CSF p-tau181, [18F]florbetapir PET, and [18F]flortaucipir PET. Participants were included based on the availability of p-tau and PET biomarker assessments collected within 9 months of each other. Exclusion criteria were a history of head trauma or magnetic resonance imaging/PET safety contraindications. No participants who met eligibility criteria were excluded.ExposuresAmyloid PET, tau PET, and CSF and plasma assessments of p-tau measured with single molecule array (Simoa) assay or enzyme-linked immunosorbent assay.Main outcomes and measuresAssociations between p-tau biomarkers with amyloid PET and tau PET.ResultsA total of 609 participants (mean [SD] age, 66.9 [13.6] years; 347 female [57%]; 262 male [43%]) were included in the study. For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau181 difference, 13%; 95% CI, 3%-22%; P = .006; p-tau217 difference, 11%; 95% CI, 3%-20%; P = .003; p-tau231 difference, 15%; 95% CI, 5%-22%; P < .001; p-tau235 difference, 9%; 95% CI, 1%-19%; P = .02) . These results were replicated with plasma p-tau181 (difference, 11%; 95% CI, 1%-22%; P = .02), p-tau217 (difference, 9%; 95% CI, 1%-19%; P = .02), p-tau231 (difference, 13%; 95% CI, 3%-24%; P = .009), and CSF p-tau181 (difference, 9%; 95% CI, 1%-21%; P = .02) in independent cohorts.Conclusions and relevanceResults of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-β accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid/tau/neurodegeneration, or A/T/(N), framework.

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Positron emission tomography as a tool for studying alcohol abuse.

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Positron emission tomography as a tool for studying alcohol abuse.

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