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Bolus infusion scheme for the adjustment of steady state [ 11 C]Flumazenil levels in the grey matter and in the blood plasma for neuroreceptor imaging.
- Source :
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NeuroImage [Neuroimage] 2020 Nov 01; Vol. 221, pp. 117160. Date of Electronic Publication: 2020 Jul 15. - Publication Year :
- 2020
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Abstract
- The use of hybrid PET/MR imaging facilitates the simultaneous investigation of challenge-related changes in ligand binding to neuroreceptors using PET, while concurrently measuring neuroactivation or blood flow with MRI. Having attained a steady state of the PET radiotracer using a bolus-infusion protocol, it is possible to observe alterations in ligand neuroreceptor binding through changes in distribution volumes. Here, we present an iterative procedure for establishing an administration scheme to obtain steady state [ <superscript>11</superscript> C]flumazenil concentrations in grey matter in the human brain. In order to achieve a steady state in the shortest possible time, the bolus infusion ratio from a previous examination was adapted to fit the subsequent examination. 17 male volunteers were included in the study. Boli and infusions with different weightings were given to the subjects and were characterised by kbol values from 74 min down to 42 min. Metabolite analysis was used to ascertain the value of unmetabolised flumazenil in the plasma, and PET imaging was used to assess its binding in the grey matter. The flumazenil time-activity curves (TACs) in the brain were decomposed into activity contributions from pure grey and white matter and analysed for 12 vol of interest (VOIs). The curves highlighted a large variability in metabolic rates between the subjects, with kbol = 54.3 min being a reliable value to provide flumazenil equilibrium conditions in the majority of the VOIs and cases. The distribution volume of flumazenil in all 12 VOIs was determined.<br />Competing Interests: Declaration of competing interest There are no known conflicts of interest.<br /> (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Humans
Male
Multimodal Imaging
Young Adult
Carbon Radioisotopes administration & dosage
Flumazenil administration & dosage
Flumazenil blood
Flumazenil pharmacokinetics
GABA Modulators administration & dosage
GABA Modulators blood
GABA Modulators pharmacokinetics
Gray Matter diagnostic imaging
Gray Matter drug effects
Gray Matter metabolism
Magnetic Resonance Imaging
Positron-Emission Tomography
Sensory Receptor Cells drug effects
Sensory Receptor Cells metabolism
White Matter diagnostic imaging
White Matter drug effects
White Matter metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9572
- Volume :
- 221
- Database :
- MEDLINE
- Journal :
- NeuroImage
- Publication Type :
- Academic Journal
- Accession number :
- 32679251
- Full Text :
- https://doi.org/10.1016/j.neuroimage.2020.117160