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Distribution of the 5-HT{sub 1A} receptor antagonist [{sup 18}F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia

Abstract

To determine whether brain and plasma equilibrium of a proposed PET tracer for 5-HT{sub 1A}, [{sup 18}F]FPWAY, can be achieved in a sufficiently short time for practical use of the brain to plasma equilibrium distribution ratio (DR) to monitor receptor availability with and without isoflurane anesthesia. Awake (n=4) and isoflurane-anesthetized (n=4) rats were administered a continuous 60 min intravenous infusion of [{sup 18}F]FPWAY with timed arterial blood sampling. Brains of the isoflurane-anesthetized rats were scanned with the ATLAS small animal PET scanner; awake rats were not. All rats were killed at 60 min and scanned postmortem for 15 min, followed by brain slicing for autoradiography. Several regions of interest (ROIs) were defined in the PET images as well as in the autoradiographic images. Regional DRs were calculated as total activity in the brain ROI divided by plasma [{sup 18}F]FPWAY activity. DRs in the anesthetized animals were constant between 30 and 60 min, indicating that near equilibrium between brain and plasma had been achieved by {proportional_to}30 min. DRs determined from postmortem PET data were higher in the isoflurane-anesthetized rats by 24% (not significant) and 33% (p=0.065) in whole brain and hippocampus, respectively. DRs determined from autoradiographic data were greater in isoflurane-anesthetized  More>>
Authors:
Tokugawa, Joji; Lang, Lixin; [1]  Ravasi, Laura; [1]  University of Milan, Institute of Radiology Sciences, Milan (Italy)]; Nakayama, Toshiyuki; Schmidt, Kathleen C; Sokoloff, Louis; [2]  Seidel, Jurgen; Green, Michael V; [3]  Eckelman, William C; [1]  Molecular Tracer LLC, Bethesda, MD (United States)]
  1. Warren Grant Magnuson Clinical Center, National Institutes of Health, Positron Emission Tomography Department, Bethesda, MD (United States)
  2. National Institute of Mental Health, National Institutes of Health, Laboratory of Cerebral Metabolism, Bethesda, MD (United States)
  3. Warren Grant Magnuson Clinical Center, National Institutes of Health, Department of Nuclear Medicine, Bethesda, MD (United States)
Publication Date:
Feb 15, 2007
Product Type:
Journal Article
Resource Relation:
Journal Name: European Journal of Nuclear Medicine and Molecular Imaging; Journal Volume: 34; Journal Issue: 2
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BLOOD; BRAIN; DRUGS; FLUORINE 18; LABELLED COMPOUNDS; RATS
OSTI ID:
20873905
Country of Origin:
Germany
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 1619-7070; TRN: DE07F5700
Availability:
Available from: http://dx.doi.org/10.1007/s00259-006-0228-x
Submitting Site:
DEN
Size:
page(s) 259-266
Announcement Date:
Jun 04, 2007

Citation Formats

Tokugawa, Joji, Lang, Lixin, Ravasi, Laura, University of Milan, Institute of Radiology Sciences, Milan (Italy)], Nakayama, Toshiyuki, Schmidt, Kathleen C, Sokoloff, Louis, Seidel, Jurgen, Green, Michael V, Eckelman, William C, and Molecular Tracer LLC, Bethesda, MD (United States)]. Distribution of the 5-HT{sub 1A} receptor antagonist [{sup 18}F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia. Germany: N. p., 2007. Web. doi:10.1007/S00259-006-0228-X.
Tokugawa, Joji, Lang, Lixin, Ravasi, Laura, University of Milan, Institute of Radiology Sciences, Milan (Italy)], Nakayama, Toshiyuki, Schmidt, Kathleen C, Sokoloff, Louis, Seidel, Jurgen, Green, Michael V, Eckelman, William C, & Molecular Tracer LLC, Bethesda, MD (United States)]. Distribution of the 5-HT{sub 1A} receptor antagonist [{sup 18}F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia. Germany. https://doi.org/10.1007/S00259-006-0228-X
Tokugawa, Joji, Lang, Lixin, Ravasi, Laura, University of Milan, Institute of Radiology Sciences, Milan (Italy)], Nakayama, Toshiyuki, Schmidt, Kathleen C, Sokoloff, Louis, Seidel, Jurgen, Green, Michael V, Eckelman, William C, and Molecular Tracer LLC, Bethesda, MD (United States)]. 2007. "Distribution of the 5-HT{sub 1A} receptor antagonist [{sup 18}F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia." Germany. https://doi.org/10.1007/S00259-006-0228-X.
@misc{etde_20873905,
title = {Distribution of the 5-HT{sub 1A} receptor antagonist [{sup 18}F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia}
author = {Tokugawa, Joji, Lang, Lixin, Ravasi, Laura, University of Milan, Institute of Radiology Sciences, Milan (Italy)], Nakayama, Toshiyuki, Schmidt, Kathleen C, Sokoloff, Louis, Seidel, Jurgen, Green, Michael V, Eckelman, William C, and Molecular Tracer LLC, Bethesda, MD (United States)]}
abstractNote = {To determine whether brain and plasma equilibrium of a proposed PET tracer for 5-HT{sub 1A}, [{sup 18}F]FPWAY, can be achieved in a sufficiently short time for practical use of the brain to plasma equilibrium distribution ratio (DR) to monitor receptor availability with and without isoflurane anesthesia. Awake (n=4) and isoflurane-anesthetized (n=4) rats were administered a continuous 60 min intravenous infusion of [{sup 18}F]FPWAY with timed arterial blood sampling. Brains of the isoflurane-anesthetized rats were scanned with the ATLAS small animal PET scanner; awake rats were not. All rats were killed at 60 min and scanned postmortem for 15 min, followed by brain slicing for autoradiography. Several regions of interest (ROIs) were defined in the PET images as well as in the autoradiographic images. Regional DRs were calculated as total activity in the brain ROI divided by plasma [{sup 18}F]FPWAY activity. DRs in the anesthetized animals were constant between 30 and 60 min, indicating that near equilibrium between brain and plasma had been achieved by {proportional_to}30 min. DRs determined from postmortem PET data were higher in the isoflurane-anesthetized rats by 24% (not significant) and 33% (p=0.065) in whole brain and hippocampus, respectively. DRs determined from autoradiographic data were greater in isoflurane-anesthetized rats in medial hippocampus, lateral hippocampus, and cerebellum by 33% (p=0.054), 63% (p<0.01), and 32% (p<0.05), respectively. [{sup 18}F]FPWAY could be an appropriate ligand for monitoring changes in receptor availability in the serotonergic system using a bolus/infusion paradigm. One possible explanation for higher DRs in anesthetized rats may be a reduction in endogenous 5-HT secretion under isoflurane anesthesia. (orig.)}
doi = {10.1007/S00259-006-0228-X}
journal = []
issue = {2}
volume = {34}
place = {Germany}
year = {2007}
month = {Feb}
}