Research article summary (published 15 Jul 2009):

Parametric mapping of 5HT1A receptor sites in the human brain with the Hypotime method: theory and normal values.

Full Abstract

The radioligand [carbonyl-(11)C]WAY-100635 ((11)C-WAY) is a PET tracer of the serotonin 5HT(1A) receptors in the human brain. It is metabolized so rapidly in the circulation that it behaves more as a chemical microsphere than as a tracer subject to continuous exchange between the circulation and brain tissue. Although reference tissue methods are useful as analyses of uptake of some radioligands with indeterminate arterial input functions, their use to analyze (11)C-WAY uptake and binding is challenged by the rapid plasma metabolism, which violates the assumption that regions of interest and reference regions continue to exchange radioligand with the circulation during the entire uptake period. Here, we proposed a method of calculation (Hypotime) that specifically uses the washout rather than the accumulation of (11)C-WAY to determine binding potentials (BP(ND)), without the use of regression analysis. METHODS: A total of 19 healthy volunteers (age range, 23-73 y) underwent PET to test the Hypotime application of the chemical microsphere properties of (11)C-WAY to identify regions of binding and nonbinding on the exclusive basis of the rate of washout of (11)C-WAY. RESULTS: The results of the Hypotime method were compared with the simplified but multilinearized reference tissue method (MLSRTM). The distribution of receptor BP(ND) obtained with Hypotime was consistent with previous autoradiography of postmortem brain tissue, with the highest values of BP(ND) recorded in the medial temporal lobe and decline of receptor availability with age. The values in the basal ganglia and cerebellum were negligible. The MLSRTM, in contrast, yielded lower BP(ND) in all regions and only weakly revealed the decline with age. CONCLUSION: The simple and computationally efficient Hypotime method gave reliable values of BP(ND) without the use of regression. The MLSRTM, on the other hand, appeared to be affected by the early disappearance of the radioligand from the circulation and the associated uncertain late presence of (11)C-WAY in the circulation.

Author information

Author/s: Møller, Mette (M); Rodell, Anders (A); Gjedde, Albert (A);

Affiliation: Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark. moller(-atsign-)pet.auh.dk

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med), published in United States. (Language: eng)

Reference: 2009-Aug; vol 50 (issue 8) : pp 1229-36

Dates: Created 2009/08/04; Completed 2009/09/28;

PMID: 19617338, status: MEDLINE (last retrieval date: 9/28/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Aged Algorithms Brain - metabolism; radionuclide imaging Female Humans Image Enhancement - methods Image Interpretation, Computer-Assisted - methods Male Metabolic Clearance Rate Middle Aged

Middle Aged Piperazines - diagnostic use; pharmacokinetics Positron-Emission Tomography - methods Pyridines - diagnostic use; pharmacokinetics Radiopharmaceuticals - diagnostic use; pharmacokinetics Receptor, Serotonin, 5-HT1A - metabolism Reference Values Reproducibility of Results Sensitivity and Specificity Tissue Distribution Young Adult

Associated Chemicals: Piperazines (0) ; Pyridines (0) ; Radiopharmaceuticals (0) ; desmethyl-WAY 100635 (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3)

Related articles

These are the highest related articles currently in the database:

• Correlation between serotonin synthesis and 5-HT1A receptor binding in the living human brain: a combined alpha-[11C]MT and [18F]MPPF positron emission tomography study. 15 May 2008
• Serotonin-1A receptor imaging in recurrent depression: replication and literature review. 29 Sep 2007
• Synthesis and initial evaluation of [11C](R)-RWAY in monkey-a new, simply labeled antagonist radioligand for imaging brain 5-HT1A receptors with PET. 18 Jun 2007
• Radiochemical synthesis and tissue distribution of p-[18F]DMPPF, a new 5-HT1A ligand for PET, in rats. 10 Jun 2006
• In vivo imaging of human cerebral nicotinic acetylcholine receptors with 2-18F-fluoro-A-85380 and PET. 30 Jan 2005
• Creation and application of a simulated database of dynamic [18f]MPPF PET acquisitions incorporating inter-individual anatomical and biological variability. 30 Oct 2006
• PET imaging of brain 5-HT1A receptors in rat in vivo with 18F-FCWAY and improvement by successful inhibition of radioligand defluorination with miconazole. 30 Jan 2006
• A novel technetium-99m radioligand for the 5-HT(1A) receptor derived from desmethyl-WAY-100635 (DWAY). 8 Nov 2001
• Synthesis and in vivo evaluation of a novel 5-HT1A receptor agonist radioligand [O-methyl- 11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione in nonhuman primates. 11 Jan 2007
• Quantification of human nicotinic acetylcholine receptors with 123I-5IA SPECT. 30 Aug 2004

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.