Imaging of δ opioid receptors in human brain by N1'- ([11C]methyl)naltrindole and PET

Igal Madar, John R. Lever, Chris M. Kinter, Ursula Scheffel, Hayden T. Ravert, John L. Musachio, William B Mathews, Robert F Dannals, J. James Frost

Research output: Contribution to journalArticle

Abstract

Recently, we have developed the positron emitting radiotracer N1'- ([11C]methyl)naltrindole ([11C]MeNTI) and demonstrated its high selectivity for δ opioid receptors in the mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In the present study, we examined the selectivity of [11C]MeNTI for the δ opioid receptor in the human brain, using positron emission tomography (PET). The regional kinetics and distribution as well as the pharmacology confirmed the selectivity of [11C]MeNTI for δ opioid receptor in the human brain. First, the regional kinetics of [11C]MeNTI are in accordance with the density of the δ opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [11C]MeNTI correlated well (r = 0.91) with the in vitro distribution of opioid sites but not with μ or κ site densities (r ≤ 0.008 or r ≤ 0.014, respectively). [11C]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen. Binding was intermediate in the amygdala and lowest in the cerebellum and thalamus. Third, studies using the competitive antagonist naltrexone demonstrated the inhibition of [11C]MeNTI binding. Naltrexone inhibition of [11C]MeNTI binding was most effective in δ receptor-rich regions, and its inhibitory potency correlated well (r = 0.88) with the regional distribution of opioid sites. [11C]MeNTI is the first radioligand which selectively labels δ opioid receptors in vive in the human brain following systemic administration. The availability of [11C]MeNTI will enable a receptor specific analysis of the role of [11C]MeNTI receptors in normal and abnormal human brain.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalSynapse
Volume24
Issue number1
DOIs
StatePublished - Sep 1996

Fingerprint

naltrindole
Opioid Receptors
Positron-Emission Tomography
Brain
Naltrexone
Opioid Analgesics
Caudate Nucleus
Putamen
Neocortex
Amygdala
Thalamus
Cerebellum
Pharmacology
Electrons

Keywords

  • Delta opioid receptors
  • Human brain
  • Methylnaltrindole
  • Positron emission tomography

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Imaging of δ opioid receptors in human brain by N1'- ([11C]methyl)naltrindole and PET. / Madar, Igal; Lever, John R.; Kinter, Chris M.; Scheffel, Ursula; Ravert, Hayden T.; Musachio, John L.; Mathews, William B; Dannals, Robert F; Frost, J. James.

In: Synapse, Vol. 24, No. 1, 09.1996, p. 19-28.

Research output: Contribution to journalArticle

Madar, Igal ; Lever, John R. ; Kinter, Chris M. ; Scheffel, Ursula ; Ravert, Hayden T. ; Musachio, John L. ; Mathews, William B ; Dannals, Robert F ; Frost, J. James. / Imaging of δ opioid receptors in human brain by N1'- ([11C]methyl)naltrindole and PET. In: Synapse. 1996 ; Vol. 24, No. 1. pp. 19-28.
@article{5f6d3e875df849b3a23792de7a86f26b,
title = "Imaging of δ opioid receptors in human brain by N1'- ([11C]methyl)naltrindole and PET",
abstract = "Recently, we have developed the positron emitting radiotracer N1'- ([11C]methyl)naltrindole ([11C]MeNTI) and demonstrated its high selectivity for δ opioid receptors in the mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In the present study, we examined the selectivity of [11C]MeNTI for the δ opioid receptor in the human brain, using positron emission tomography (PET). The regional kinetics and distribution as well as the pharmacology confirmed the selectivity of [11C]MeNTI for δ opioid receptor in the human brain. First, the regional kinetics of [11C]MeNTI are in accordance with the density of the δ opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [11C]MeNTI correlated well (r = 0.91) with the in vitro distribution of opioid sites but not with μ or κ site densities (r ≤ 0.008 or r ≤ 0.014, respectively). [11C]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen. Binding was intermediate in the amygdala and lowest in the cerebellum and thalamus. Third, studies using the competitive antagonist naltrexone demonstrated the inhibition of [11C]MeNTI binding. Naltrexone inhibition of [11C]MeNTI binding was most effective in δ receptor-rich regions, and its inhibitory potency correlated well (r = 0.88) with the regional distribution of opioid sites. [11C]MeNTI is the first radioligand which selectively labels δ opioid receptors in vive in the human brain following systemic administration. The availability of [11C]MeNTI will enable a receptor specific analysis of the role of [11C]MeNTI receptors in normal and abnormal human brain.",
keywords = "Delta opioid receptors, Human brain, Methylnaltrindole, Positron emission tomography",
author = "Igal Madar and Lever, {John R.} and Kinter, {Chris M.} and Ursula Scheffel and Ravert, {Hayden T.} and Musachio, {John L.} and Mathews, {William B} and Dannals, {Robert F} and Frost, {J. James}",
year = "1996",
month = "9",
doi = "10.1002/(SICI)1098-2396(199609)24:1<19::AID-SYN3>3.0.CO;2-J",
language = "English (US)",
volume = "24",
pages = "19--28",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Imaging of δ opioid receptors in human brain by N1'- ([11C]methyl)naltrindole and PET

AU - Madar, Igal

AU - Lever, John R.

AU - Kinter, Chris M.

AU - Scheffel, Ursula

AU - Ravert, Hayden T.

AU - Musachio, John L.

AU - Mathews, William B

AU - Dannals, Robert F

AU - Frost, J. James

PY - 1996/9

Y1 - 1996/9

N2 - Recently, we have developed the positron emitting radiotracer N1'- ([11C]methyl)naltrindole ([11C]MeNTI) and demonstrated its high selectivity for δ opioid receptors in the mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In the present study, we examined the selectivity of [11C]MeNTI for the δ opioid receptor in the human brain, using positron emission tomography (PET). The regional kinetics and distribution as well as the pharmacology confirmed the selectivity of [11C]MeNTI for δ opioid receptor in the human brain. First, the regional kinetics of [11C]MeNTI are in accordance with the density of the δ opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [11C]MeNTI correlated well (r = 0.91) with the in vitro distribution of opioid sites but not with μ or κ site densities (r ≤ 0.008 or r ≤ 0.014, respectively). [11C]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen. Binding was intermediate in the amygdala and lowest in the cerebellum and thalamus. Third, studies using the competitive antagonist naltrexone demonstrated the inhibition of [11C]MeNTI binding. Naltrexone inhibition of [11C]MeNTI binding was most effective in δ receptor-rich regions, and its inhibitory potency correlated well (r = 0.88) with the regional distribution of opioid sites. [11C]MeNTI is the first radioligand which selectively labels δ opioid receptors in vive in the human brain following systemic administration. The availability of [11C]MeNTI will enable a receptor specific analysis of the role of [11C]MeNTI receptors in normal and abnormal human brain.

AB - Recently, we have developed the positron emitting radiotracer N1'- ([11C]methyl)naltrindole ([11C]MeNTI) and demonstrated its high selectivity for δ opioid receptors in the mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In the present study, we examined the selectivity of [11C]MeNTI for the δ opioid receptor in the human brain, using positron emission tomography (PET). The regional kinetics and distribution as well as the pharmacology confirmed the selectivity of [11C]MeNTI for δ opioid receptor in the human brain. First, the regional kinetics of [11C]MeNTI are in accordance with the density of the δ opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [11C]MeNTI correlated well (r = 0.91) with the in vitro distribution of opioid sites but not with μ or κ site densities (r ≤ 0.008 or r ≤ 0.014, respectively). [11C]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen. Binding was intermediate in the amygdala and lowest in the cerebellum and thalamus. Third, studies using the competitive antagonist naltrexone demonstrated the inhibition of [11C]MeNTI binding. Naltrexone inhibition of [11C]MeNTI binding was most effective in δ receptor-rich regions, and its inhibitory potency correlated well (r = 0.88) with the regional distribution of opioid sites. [11C]MeNTI is the first radioligand which selectively labels δ opioid receptors in vive in the human brain following systemic administration. The availability of [11C]MeNTI will enable a receptor specific analysis of the role of [11C]MeNTI receptors in normal and abnormal human brain.

KW - Delta opioid receptors

KW - Human brain

KW - Methylnaltrindole

KW - Positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=0029789198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029789198&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2396(199609)24:1<19::AID-SYN3>3.0.CO;2-J

DO - 10.1002/(SICI)1098-2396(199609)24:1<19::AID-SYN3>3.0.CO;2-J

M3 - Article

C2 - 9046073

AN - SCOPUS:0029789198

VL - 24

SP - 19

EP - 28

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 1

ER -