Test-retest variability of serotonin 5-HT(2A) receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

Gwenn Smith, Julie C. Price, Brian J. Lopresti, Yiyun Huang, Norman Simpson, Daniel Holt, N. Scott Mason, Carolyn Cidis Meltzer, Robert A. Sweet, Thomas Nichols, Donald Sashin, Chester A. Mathis

Research output: Contribution to journalArticle

Abstract

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT(2A) receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV). estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT(2A) receptors determined by postmortem autoradiographic studies (r2 = 0.95, P <0.001 for the 4C model and r2 = 0.96, P <0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood- brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT(2A) receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT(2A) receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT(2A) receptors.

Original languageEnglish (US)
Pages (from-to)380-392
Number of pages13
JournalSynapse
Volume30
Issue number4
DOIs
StatePublished - Dec 1998
Externally publishedYes

Fingerprint

Receptor, Serotonin, 5-HT2A
Positron-Emission Tomography
Serotonin
Brain
altanserin
Serotonin Receptors
Blood-Brain Barrier
Thalamus
Mood Disorders
Cerebellum
Radioactivity
Dementia
Schizophrenia

Keywords

  • 5-HT(2A)
  • Imaging
  • Positron emission tomography (PET)
  • Serotonin receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Test-retest variability of serotonin 5-HT(2A) receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. / Smith, Gwenn; Price, Julie C.; Lopresti, Brian J.; Huang, Yiyun; Simpson, Norman; Holt, Daniel; Mason, N. Scott; Meltzer, Carolyn Cidis; Sweet, Robert A.; Nichols, Thomas; Sashin, Donald; Mathis, Chester A.

In: Synapse, Vol. 30, No. 4, 12.1998, p. 380-392.

Research output: Contribution to journalArticle

Smith, Gwenn ; Price, Julie C. ; Lopresti, Brian J. ; Huang, Yiyun ; Simpson, Norman ; Holt, Daniel ; Mason, N. Scott ; Meltzer, Carolyn Cidis ; Sweet, Robert A. ; Nichols, Thomas ; Sashin, Donald ; Mathis, Chester A. / Test-retest variability of serotonin 5-HT(2A) receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. In: Synapse. 1998 ; Vol. 30, No. 4. pp. 380-392.
@article{cf441c81deff479fbf0f0ae941c3d120,
title = "Test-retest variability of serotonin 5-HT(2A) receptor binding measured with positron emission tomography and [18F]altanserin in the human brain",
abstract = "The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT(2A) receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV). estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13{\%} or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20{\%}). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12{\%} or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10{\%}. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT(2A) receptors determined by postmortem autoradiographic studies (r2 = 0.95, P <0.001 for the 4C model and r2 = 0.96, P <0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25{\%} of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood- brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT(2A) receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT(2A) receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT(2A) receptors.",
keywords = "5-HT(2A), Imaging, Positron emission tomography (PET), Serotonin receptor",
author = "Gwenn Smith and Price, {Julie C.} and Lopresti, {Brian J.} and Yiyun Huang and Norman Simpson and Daniel Holt and Mason, {N. Scott} and Meltzer, {Carolyn Cidis} and Sweet, {Robert A.} and Thomas Nichols and Donald Sashin and Mathis, {Chester A.}",
year = "1998",
month = "12",
doi = "10.1002/(SICI)1098-2396(199812)30:4<380::AID-SYN5>3.0.CO;2-U",
language = "English (US)",
volume = "30",
pages = "380--392",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Test-retest variability of serotonin 5-HT(2A) receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

AU - Smith, Gwenn

AU - Price, Julie C.

AU - Lopresti, Brian J.

AU - Huang, Yiyun

AU - Simpson, Norman

AU - Holt, Daniel

AU - Mason, N. Scott

AU - Meltzer, Carolyn Cidis

AU - Sweet, Robert A.

AU - Nichols, Thomas

AU - Sashin, Donald

AU - Mathis, Chester A.

PY - 1998/12

Y1 - 1998/12

N2 - The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT(2A) receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV). estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT(2A) receptors determined by postmortem autoradiographic studies (r2 = 0.95, P <0.001 for the 4C model and r2 = 0.96, P <0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood- brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT(2A) receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT(2A) receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT(2A) receptors.

AB - The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT(2A) receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV). estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT(2A) receptors determined by postmortem autoradiographic studies (r2 = 0.95, P <0.001 for the 4C model and r2 = 0.96, P <0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood- brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT(2A) receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT(2A) receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT(2A) receptors.

KW - 5-HT(2A)

KW - Imaging

KW - Positron emission tomography (PET)

KW - Serotonin receptor

UR - http://www.scopus.com/inward/record.url?scp=7844225508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7844225508&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2396(199812)30:4<380::AID-SYN5>3.0.CO;2-U

DO - 10.1002/(SICI)1098-2396(199812)30:4<380::AID-SYN5>3.0.CO;2-U

M3 - Article

C2 - 9826230

AN - SCOPUS:7844225508

VL - 30

SP - 380

EP - 392

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 4

ER -