Development of a tracer kinetic plasma input model for (R)-[ 11C]PK11195 brain studies

Marc A. Kropholler, Ronald Boellaard, Alie Schuitemaker, Bart N M Van Berckel, Gert Luurtsema, Albert D. Windhorst, Adriaan A. Lammertsma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

(R)-[11C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/k2 ratio, k4, or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[ 11C]PK11195 PET brain studies. Simulations showed that fixing the K1/k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies.

Original languageEnglish
Pages (from-to)842-851
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume25
Issue number7
DOIs
Publication statusPublished - 12 Jul 2005

Cite this

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title = "Development of a tracer kinetic plasma input model for (R)-[ 11C]PK11195 brain studies",
abstract = "(R)-[11C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/k2 ratio, k4, or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[ 11C]PK11195 PET brain studies. Simulations showed that fixing the K1/k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies.",
keywords = "Compartmental models, Microglia, Peripheral benzodiazepine receptor, PET, PK11195",
author = "Kropholler, {Marc A.} and Ronald Boellaard and Alie Schuitemaker and {Van Berckel}, {Bart N M} and Gert Luurtsema and Windhorst, {Albert D.} and Lammertsma, {Adriaan A.}",
year = "2005",
month = "7",
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doi = "10.1038/sj.jcbfm.9600092",
language = "English",
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pages = "842--851",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
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Development of a tracer kinetic plasma input model for (R)-[ 11C]PK11195 brain studies. / Kropholler, Marc A.; Boellaard, Ronald; Schuitemaker, Alie; Van Berckel, Bart N M; Luurtsema, Gert; Windhorst, Albert D.; Lammertsma, Adriaan A.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 25, No. 7, 12.07.2005, p. 842-851.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Development of a tracer kinetic plasma input model for (R)-[ 11C]PK11195 brain studies

AU - Kropholler, Marc A.

AU - Boellaard, Ronald

AU - Schuitemaker, Alie

AU - Van Berckel, Bart N M

AU - Luurtsema, Gert

AU - Windhorst, Albert D.

AU - Lammertsma, Adriaan A.

PY - 2005/7/12

Y1 - 2005/7/12

N2 - (R)-[11C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/k2 ratio, k4, or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[ 11C]PK11195 PET brain studies. Simulations showed that fixing the K1/k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies.

AB - (R)-[11C]PK11195 ([1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/k2 ratio, k4, or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[ 11C]PK11195 PET brain studies. Simulations showed that fixing the K1/k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies.

KW - Compartmental models

KW - Microglia

KW - Peripheral benzodiazepine receptor

KW - PET

KW - PK11195

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U2 - 10.1038/sj.jcbfm.9600092

DO - 10.1038/sj.jcbfm.9600092

M3 - Article

VL - 25

SP - 842

EP - 851

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 7

ER -