Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain

Jonathon A. Nye, John R. Votaw, Nachwa Jarkas, David Purselle, Vernon Camp, James D. Bremner, Clinton D. Kilts, Charles Nemeroff, Mark M. Goodman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino- 4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain. Methods: Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2-and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results: The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion: 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.

Original languageEnglish
Pages (from-to)2018-2025
Number of pages8
JournalJournal of Nuclear Medicine
Volume49
Issue number12
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Brain
Raphe Nuclei
Mesencephalon
Cerebellum
Volunteers
Catheters
Injections
Research

Keywords

  • Kinetic modeling
  • PET
  • Serotonin transporter

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Nye, J. A., Votaw, J. R., Jarkas, N., Purselle, D., Camp, V., Bremner, J. D., ... Goodman, M. M. (2008). Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain. Journal of Nuclear Medicine, 49(12), 2018-2025. https://doi.org/10.2967/jnumed.108.054262

Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain. / Nye, Jonathon A.; Votaw, John R.; Jarkas, Nachwa; Purselle, David; Camp, Vernon; Bremner, James D.; Kilts, Clinton D.; Nemeroff, Charles; Goodman, Mark M.

In: Journal of Nuclear Medicine, Vol. 49, No. 12, 01.12.2008, p. 2018-2025.

Research output: Contribution to journalArticle

Nye, JA, Votaw, JR, Jarkas, N, Purselle, D, Camp, V, Bremner, JD, Kilts, CD, Nemeroff, C & Goodman, MM 2008, 'Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain', Journal of Nuclear Medicine, vol. 49, no. 12, pp. 2018-2025. https://doi.org/10.2967/jnumed.108.054262
Nye, Jonathon A. ; Votaw, John R. ; Jarkas, Nachwa ; Purselle, David ; Camp, Vernon ; Bremner, James D. ; Kilts, Clinton D. ; Nemeroff, Charles ; Goodman, Mark M. / Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain. In: Journal of Nuclear Medicine. 2008 ; Vol. 49, No. 12. pp. 2018-2025.
@article{3ddc5f1024fb4ef4b39719612a6ad81b,
title = "Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain",
abstract = "The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino- 4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain. Methods: Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2-and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results: The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion: 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.",
keywords = "Kinetic modeling, PET, Serotonin transporter",
author = "Nye, {Jonathon A.} and Votaw, {John R.} and Nachwa Jarkas and David Purselle and Vernon Camp and Bremner, {James D.} and Kilts, {Clinton D.} and Charles Nemeroff and Goodman, {Mark M.}",
year = "2008",
month = "12",
day = "1",
doi = "10.2967/jnumed.108.054262",
language = "English",
volume = "49",
pages = "2018--2025",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "12",

}

TY - JOUR

T1 - Compartmental modeling of11C-HOMADAM binding to the serotonin transporter in the healthy human brain

AU - Nye, Jonathon A.

AU - Votaw, John R.

AU - Jarkas, Nachwa

AU - Purselle, David

AU - Camp, Vernon

AU - Bremner, James D.

AU - Kilts, Clinton D.

AU - Nemeroff, Charles

AU - Goodman, Mark M.

PY - 2008/12/1

Y1 - 2008/12/1

N2 - The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino- 4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain. Methods: Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2-and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results: The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion: 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.

AB - The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino- 4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain. Methods: Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2-and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results: The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion: 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.

KW - Kinetic modeling

KW - PET

KW - Serotonin transporter

UR - http://www.scopus.com/inward/record.url?scp=57149102510&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57149102510&partnerID=8YFLogxK

U2 - 10.2967/jnumed.108.054262

DO - 10.2967/jnumed.108.054262

M3 - Article

VL - 49

SP - 2018

EP - 2025

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 12

ER -