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European Journal of Nuclear Medicine and Molecular Imaging

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01-02-2007 | Original article

Distribution of the 5-HT_1A receptor antagonist [¹⁸F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia

Authors: Joji Tokugawa, Laura Ravasi, Toshiyuki Nakayama, Lixin Lang, Kathleen C. Schmidt, Jurgen Seidel, Michael V. Green, Louis Sokoloff, William C. Eckelman

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2007

Abstract

Purpose

To determine whether brain and plasma equilibrium of a proposed PET tracer for 5-HT_1A, [¹⁸F]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.

Methods

Awake (n=4) and isoflurane-anesthetized (n=4) rats were administered a continuous 60 min intravenous infusion of [¹⁸F]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 [¹⁸F]FPWAY activity.

Results

DRs in the anesthetized animals were constant between 30 and 60 min, indicating that near equilibrium between brain and plasma had been achieved by ∼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.

Conclusion

[¹⁸F]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.

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Title: Distribution of the 5-HT1A receptor antagonist [18F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia
Authors: Joji Tokugawa
Laura Ravasi
Toshiyuki Nakayama
Lixin Lang
Kathleen C. Schmidt
Jurgen Seidel
Michael V. Green
Louis Sokoloff
William C. Eckelman
Publication date: 01-02-2007
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0228-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Distribution of the 5-HT_1A receptor antagonist [¹⁸F]FPWAY in blood and brain of the rat with and without isoflurane anesthesia

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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