[11C]Mirtazapine for PET neuroimaging

Radiosynthesis and initial evaluation in the living porcine brain

Katalin Marthi, Dirk Bender, Albert Gjedde, Donald F. Smith

Research output: Contribution to journalArticle

Abstract

We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for positron emission tomography (PET) and evaluated its regional kinetics in the living porcine brain. We produced [N-methyl-11C]mirtazapine with a radiochemical-purity >98% in a 21% decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with [11C]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-11C]mirtazapine entered the brain readily and, under baseline conditions, it had an apparent volume of distribution (Ve′) of 9-13 in the basal ganglia, thalamus, and frontal cortex. Reference region and graphical analyses based on a one-compartment model showed that the binding of [N-methyl-11C]mirtazapine was reversible, with an apparent binding potential of more than two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly displaced [N-methyl-11C]mirtazapine from binding sites in the basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum and olfactory tubercle). Thus, [N-methyl-11C]mirtazapine showed rapid passage into the living brain, slow metabolism in blood, and reversible, competitive binding, which may make it useful for PET neuroimaging of neuroreceptors involved in antidepressant actions.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalEuropean Neuropsychopharmacology
Volume12
Issue number5
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Neuroimaging
Positron-Emission Tomography
Swine
Brain
Frontal Lobe
Thalamus
Basal Ganglia
Antidepressive Agents
Second-Generation Antidepressive Agents
Competitive Binding
mirtazapine
Alkylation
Sensory Receptor Cells
Cerebellum
Binding Sites
High Pressure Liquid Chromatography

Keywords

  • [C]Mirtazapine
  • Antidepressant
  • PET neuroimaging
  • Porcine brain
  • Tetracyclic drug

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)

Cite this

[11C]Mirtazapine for PET neuroimaging : Radiosynthesis and initial evaluation in the living porcine brain. / Marthi, Katalin; Bender, Dirk; Gjedde, Albert; Smith, Donald F.

In: European Neuropsychopharmacology, Vol. 12, No. 5, 10.2002, p. 427-432.

Research output: Contribution to journalArticle

Marthi, Katalin ; Bender, Dirk ; Gjedde, Albert ; Smith, Donald F. / [11C]Mirtazapine for PET neuroimaging : Radiosynthesis and initial evaluation in the living porcine brain. In: European Neuropsychopharmacology. 2002 ; Vol. 12, No. 5. pp. 427-432.
@article{2234ff5584fd47f1a90107dcdf72bee5,
title = "[11C]Mirtazapine for PET neuroimaging: Radiosynthesis and initial evaluation in the living porcine brain",
abstract = "We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for positron emission tomography (PET) and evaluated its regional kinetics in the living porcine brain. We produced [N-methyl-11C]mirtazapine with a radiochemical-purity >98{\%} in a 21{\%} decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with [11C]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-11C]mirtazapine entered the brain readily and, under baseline conditions, it had an apparent volume of distribution (Ve′) of 9-13 in the basal ganglia, thalamus, and frontal cortex. Reference region and graphical analyses based on a one-compartment model showed that the binding of [N-methyl-11C]mirtazapine was reversible, with an apparent binding potential of more than two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly displaced [N-methyl-11C]mirtazapine from binding sites in the basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum and olfactory tubercle). Thus, [N-methyl-11C]mirtazapine showed rapid passage into the living brain, slow metabolism in blood, and reversible, competitive binding, which may make it useful for PET neuroimaging of neuroreceptors involved in antidepressant actions.",
keywords = "[C]Mirtazapine, Antidepressant, PET neuroimaging, Porcine brain, Tetracyclic drug",
author = "Katalin Marthi and Dirk Bender and Albert Gjedde and Smith, {Donald F.}",
year = "2002",
month = "10",
doi = "10.1016/S0924-977X(02)00049-4",
language = "English (US)",
volume = "12",
pages = "427--432",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - [11C]Mirtazapine for PET neuroimaging

T2 - Radiosynthesis and initial evaluation in the living porcine brain

AU - Marthi, Katalin

AU - Bender, Dirk

AU - Gjedde, Albert

AU - Smith, Donald F.

PY - 2002/10

Y1 - 2002/10

N2 - We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for positron emission tomography (PET) and evaluated its regional kinetics in the living porcine brain. We produced [N-methyl-11C]mirtazapine with a radiochemical-purity >98% in a 21% decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with [11C]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-11C]mirtazapine entered the brain readily and, under baseline conditions, it had an apparent volume of distribution (Ve′) of 9-13 in the basal ganglia, thalamus, and frontal cortex. Reference region and graphical analyses based on a one-compartment model showed that the binding of [N-methyl-11C]mirtazapine was reversible, with an apparent binding potential of more than two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly displaced [N-methyl-11C]mirtazapine from binding sites in the basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum and olfactory tubercle). Thus, [N-methyl-11C]mirtazapine showed rapid passage into the living brain, slow metabolism in blood, and reversible, competitive binding, which may make it useful for PET neuroimaging of neuroreceptors involved in antidepressant actions.

AB - We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for positron emission tomography (PET) and evaluated its regional kinetics in the living porcine brain. We produced [N-methyl-11C]mirtazapine with a radiochemical-purity >98% in a 21% decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with [11C]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-11C]mirtazapine entered the brain readily and, under baseline conditions, it had an apparent volume of distribution (Ve′) of 9-13 in the basal ganglia, thalamus, and frontal cortex. Reference region and graphical analyses based on a one-compartment model showed that the binding of [N-methyl-11C]mirtazapine was reversible, with an apparent binding potential of more than two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly displaced [N-methyl-11C]mirtazapine from binding sites in the basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum and olfactory tubercle). Thus, [N-methyl-11C]mirtazapine showed rapid passage into the living brain, slow metabolism in blood, and reversible, competitive binding, which may make it useful for PET neuroimaging of neuroreceptors involved in antidepressant actions.

KW - [C]Mirtazapine

KW - Antidepressant

KW - PET neuroimaging

KW - Porcine brain

KW - Tetracyclic drug

UR - http://www.scopus.com/inward/record.url?scp=0036771734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036771734&partnerID=8YFLogxK

U2 - 10.1016/S0924-977X(02)00049-4

DO - 10.1016/S0924-977X(02)00049-4

M3 - Article

VL - 12

SP - 427

EP - 432

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

IS - 5

ER -