Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers

A PET study with 2-18F-FA-85380

Alexey G. Mukhin, Alane S. Kimes, Svetlana I. Chefer, John A. Matochik, Carlo S. Contoreggi, Andrew Horti, D. Bruce Vaupel, Olga Pavlova, Elliot A. Stein

Research output: Contribution to journalArticle

Abstract

Assays of human postmortem brain tissue have revealed that smokers have greater densities of high-affinity nicotinic acetylcholine receptors (nAChRs) in several brain regions than do nonsmokers or exsmokers. Quantitative PET imaging of nAChRs in humans has recently been reported using the α4β2* subtype-specific radioligand 2-18F-FA-85380 (2FA). Methods: We used PET and 2FA to measure total volumes of distribution corrected for the free fraction of 2FA in plasma (VT/fP) in 10 nonsmokers and 6 heavy smokers (>14 cigarettes/d; abstinent for >36 h). Dynamic PET scans were performed over 8 h, commencing immediately after a bolus injection of 2FA. Anatomic sampling was performed on PET images that were coregistered to MR images acquired from each volunteer. Data were analyzed by Logan plots and by 1- and 2-tissue-compartment models using unbound, unmetabolized arterial 2FA concentration as the input function. Results: All modeling methods yielded similar results. VT/fP was significantly higher in smokers than in nonsmokers in all brain regions tested, except the thalamus. We used measures of VT/fP and estimates of nondisplaceable volume of distribution and found 25%-200% higher values in smokers than in nonsmokers for the volume of distribution for the specific binding compartment in the frontal cortex, midbrain, putamen, pons, cerebellum, and corpus callosum. These findings were consistent with voxel-based analysis using statistical parametric mapping. Conclusion: Our findings suggest that PET with 2FA can be used to study the role of nicotine-induced upregulation of nAChRs in active smokers and during smoking cessation.

Original languageEnglish (US)
Pages (from-to)1628-1635
Number of pages8
JournalJournal of Nuclear Medicine
Volume49
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Nicotinic Receptors
Brain
Pons
Corpus Callosum
Putamen
Frontal Lobe
Smoking Cessation
Mesencephalon
Thalamus
Nicotine
Tobacco Products
Positron-Emission Tomography
Cerebellum
Volunteers
Up-Regulation
Injections

Keywords

  • Molecular imaging
  • Neuroimaging
  • Nicotinic acetylcholine receptors
  • PET
  • Radiotracer tissue kinetics
  • Smoking

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Mukhin, A. G., Kimes, A. S., Chefer, S. I., Matochik, J. A., Contoreggi, C. S., Horti, A., ... Stein, E. A. (2008). Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers: A PET study with 2-18F-FA-85380. Journal of Nuclear Medicine, 49(10), 1628-1635. https://doi.org/10.2967/jnumed.108.050716

Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers : A PET study with 2-18F-FA-85380. / Mukhin, Alexey G.; Kimes, Alane S.; Chefer, Svetlana I.; Matochik, John A.; Contoreggi, Carlo S.; Horti, Andrew; Vaupel, D. Bruce; Pavlova, Olga; Stein, Elliot A.

In: Journal of Nuclear Medicine, Vol. 49, No. 10, 01.10.2008, p. 1628-1635.

Research output: Contribution to journalArticle

Mukhin, AG, Kimes, AS, Chefer, SI, Matochik, JA, Contoreggi, CS, Horti, A, Vaupel, DB, Pavlova, O & Stein, EA 2008, 'Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers: A PET study with 2-18F-FA-85380', Journal of Nuclear Medicine, vol. 49, no. 10, pp. 1628-1635. https://doi.org/10.2967/jnumed.108.050716
Mukhin, Alexey G. ; Kimes, Alane S. ; Chefer, Svetlana I. ; Matochik, John A. ; Contoreggi, Carlo S. ; Horti, Andrew ; Vaupel, D. Bruce ; Pavlova, Olga ; Stein, Elliot A. / Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers : A PET study with 2-18F-FA-85380. In: Journal of Nuclear Medicine. 2008 ; Vol. 49, No. 10. pp. 1628-1635.
@article{fc73cfe3d4bb4fa7b40fce832e152cce,
title = "Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers: A PET study with 2-18F-FA-85380",
abstract = "Assays of human postmortem brain tissue have revealed that smokers have greater densities of high-affinity nicotinic acetylcholine receptors (nAChRs) in several brain regions than do nonsmokers or exsmokers. Quantitative PET imaging of nAChRs in humans has recently been reported using the α4β2* subtype-specific radioligand 2-18F-FA-85380 (2FA). Methods: We used PET and 2FA to measure total volumes of distribution corrected for the free fraction of 2FA in plasma (VT/fP) in 10 nonsmokers and 6 heavy smokers (>14 cigarettes/d; abstinent for >36 h). Dynamic PET scans were performed over 8 h, commencing immediately after a bolus injection of 2FA. Anatomic sampling was performed on PET images that were coregistered to MR images acquired from each volunteer. Data were analyzed by Logan plots and by 1- and 2-tissue-compartment models using unbound, unmetabolized arterial 2FA concentration as the input function. Results: All modeling methods yielded similar results. VT/fP was significantly higher in smokers than in nonsmokers in all brain regions tested, except the thalamus. We used measures of VT/fP and estimates of nondisplaceable volume of distribution and found 25{\%}-200{\%} higher values in smokers than in nonsmokers for the volume of distribution for the specific binding compartment in the frontal cortex, midbrain, putamen, pons, cerebellum, and corpus callosum. These findings were consistent with voxel-based analysis using statistical parametric mapping. Conclusion: Our findings suggest that PET with 2FA can be used to study the role of nicotine-induced upregulation of nAChRs in active smokers and during smoking cessation.",
keywords = "Molecular imaging, Neuroimaging, Nicotinic acetylcholine receptors, PET, Radiotracer tissue kinetics, Smoking",
author = "Mukhin, {Alexey G.} and Kimes, {Alane S.} and Chefer, {Svetlana I.} and Matochik, {John A.} and Contoreggi, {Carlo S.} and Andrew Horti and Vaupel, {D. Bruce} and Olga Pavlova and Stein, {Elliot A.}",
year = "2008",
month = "10",
day = "1",
doi = "10.2967/jnumed.108.050716",
language = "English (US)",
volume = "49",
pages = "1628--1635",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "10",

}

TY - JOUR

T1 - Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers

T2 - A PET study with 2-18F-FA-85380

AU - Mukhin, Alexey G.

AU - Kimes, Alane S.

AU - Chefer, Svetlana I.

AU - Matochik, John A.

AU - Contoreggi, Carlo S.

AU - Horti, Andrew

AU - Vaupel, D. Bruce

AU - Pavlova, Olga

AU - Stein, Elliot A.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Assays of human postmortem brain tissue have revealed that smokers have greater densities of high-affinity nicotinic acetylcholine receptors (nAChRs) in several brain regions than do nonsmokers or exsmokers. Quantitative PET imaging of nAChRs in humans has recently been reported using the α4β2* subtype-specific radioligand 2-18F-FA-85380 (2FA). Methods: We used PET and 2FA to measure total volumes of distribution corrected for the free fraction of 2FA in plasma (VT/fP) in 10 nonsmokers and 6 heavy smokers (>14 cigarettes/d; abstinent for >36 h). Dynamic PET scans were performed over 8 h, commencing immediately after a bolus injection of 2FA. Anatomic sampling was performed on PET images that were coregistered to MR images acquired from each volunteer. Data were analyzed by Logan plots and by 1- and 2-tissue-compartment models using unbound, unmetabolized arterial 2FA concentration as the input function. Results: All modeling methods yielded similar results. VT/fP was significantly higher in smokers than in nonsmokers in all brain regions tested, except the thalamus. We used measures of VT/fP and estimates of nondisplaceable volume of distribution and found 25%-200% higher values in smokers than in nonsmokers for the volume of distribution for the specific binding compartment in the frontal cortex, midbrain, putamen, pons, cerebellum, and corpus callosum. These findings were consistent with voxel-based analysis using statistical parametric mapping. Conclusion: Our findings suggest that PET with 2FA can be used to study the role of nicotine-induced upregulation of nAChRs in active smokers and during smoking cessation.

AB - Assays of human postmortem brain tissue have revealed that smokers have greater densities of high-affinity nicotinic acetylcholine receptors (nAChRs) in several brain regions than do nonsmokers or exsmokers. Quantitative PET imaging of nAChRs in humans has recently been reported using the α4β2* subtype-specific radioligand 2-18F-FA-85380 (2FA). Methods: We used PET and 2FA to measure total volumes of distribution corrected for the free fraction of 2FA in plasma (VT/fP) in 10 nonsmokers and 6 heavy smokers (>14 cigarettes/d; abstinent for >36 h). Dynamic PET scans were performed over 8 h, commencing immediately after a bolus injection of 2FA. Anatomic sampling was performed on PET images that were coregistered to MR images acquired from each volunteer. Data were analyzed by Logan plots and by 1- and 2-tissue-compartment models using unbound, unmetabolized arterial 2FA concentration as the input function. Results: All modeling methods yielded similar results. VT/fP was significantly higher in smokers than in nonsmokers in all brain regions tested, except the thalamus. We used measures of VT/fP and estimates of nondisplaceable volume of distribution and found 25%-200% higher values in smokers than in nonsmokers for the volume of distribution for the specific binding compartment in the frontal cortex, midbrain, putamen, pons, cerebellum, and corpus callosum. These findings were consistent with voxel-based analysis using statistical parametric mapping. Conclusion: Our findings suggest that PET with 2FA can be used to study the role of nicotine-induced upregulation of nAChRs in active smokers and during smoking cessation.

KW - Molecular imaging

KW - Neuroimaging

KW - Nicotinic acetylcholine receptors

KW - PET

KW - Radiotracer tissue kinetics

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=53749101043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53749101043&partnerID=8YFLogxK

U2 - 10.2967/jnumed.108.050716

DO - 10.2967/jnumed.108.050716

M3 - Article

VL - 49

SP - 1628

EP - 1635

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 10

ER -