Characterization of the SPECT 5-HT2A receptor ligand I-123-R91150 in healthy volunteers

Part 1 - Pseudoequilibrium interval and quantification methods

A M Catafau, M Danus, S Bullich, J Llop, J Perich, Vincent Joseph Cunningham, P Plaza, M M Penengo, J L H Eersels, L Squassante, D Ros, M Barbanoj

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

With the aim of characterizing radioiodinated 4-amino-N-1[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2- methoxybenzamide (I-123-R91150) as a SPECT ligand for subtype 2A of the 5-hydroxytryptamine receptor (5-HT2A), tracer kinetic compartmental analyses were compared with the tissue ratio method (TR). The pseudoequilibrium interval after a single bolus injection was identified, and a reference database of specific uptake ratio (SUR) values was obtained. Within-scan and between-subject variability was also assessed. Methods: Nineteen healthy men (mean age SD, 24.4 +/- 3.3 y) were included and separated into 2 groups. Dynamic scans with venous blood sampling from 0 to 470 min after a single bolus injection of I-123-R91150 was completed for 7 of the 9 subjects included in group A, and in one of them compartmental modeling was performed with an arterial blood input function using 1-tissue-compartment (1TC) and 2-tissue-compartment (2TC) models. Binding potential (BP) using the simplified reference tissue model (SRTM) (BPSRTM) and SUR values using TR over time were also calculated. The 10 remaining subjects (group B) underwent a single scan at pseudoequilibrium with the aim of improving the precision of mean normal SUR estimates. Regions of interest in cortical regions and basal ganglia for specific uptake, and in cerebellum for nonspecific uptake, were manually drawn on each subject's MR images and translated to the corresponding SPECT slices after coregistration. Results: The 1TC model correlated well with the 2TC model (BP2TC = 1.04-BP1TC - 0.01, R-2 =0.98), and both methods correlated with BPSRTM and SUR with little bias (BP1TC = 1.10 BPSRTM + 0.03, R-2 = 0.98; BP2TC = 1.15 BPSRTM + 0.01 R-2 - 0.98; BPSRTM = 0.99 SURmean + 0.01, R-2 - 0.98). SUR values stabilized from 180 min after injection in most cortical regions, ranging from 0.51 +/- 0.10 in the orbitofrontal region to 0.27 +/- 0.09 in the parietal region. Within-scan and between-subject variability among regions ranged from 10% to 14.8%, and from 18.3% to 35.4%, respectively. Conclusion: I-123-R91150 distribution agrees with autoradiography results, showing highly specific binding in cortical regions. The correlations found among 1TC, 2TC, SRTM, and TR outcome measurements support the use of TR for quantification of 5-HT2A receptor binding with I-123-R91150 SPECT and a simple protocol avoiding arterial blood sampling and serial scanning over time.

Original languageEnglish
Pages (from-to)919-928
Number of pages10
JournalJournal of Nuclear Medicine
Volume47
Issue number6
Publication statusPublished - Jun 2006

Keywords

  • molecular imaging
  • neurotransmission
  • SPECT
  • I-123-R91150
  • 5-HT2A
  • photon-emission-tomography
  • human-brain
  • binding index
  • MDMA ecstasy
  • test-retest
  • I-123-5-I-R91150
  • reproducibility
  • displacement
  • transporters

Cite this

Catafau, A. M., Danus, M., Bullich, S., Llop, J., Perich, J., Cunningham, V. J., ... Barbanoj, M. (2006). Characterization of the SPECT 5-HT2A receptor ligand I-123-R91150 in healthy volunteers: Part 1 - Pseudoequilibrium interval and quantification methods. Journal of Nuclear Medicine, 47(6), 919-928.

Characterization of the SPECT 5-HT2A receptor ligand I-123-R91150 in healthy volunteers : Part 1 - Pseudoequilibrium interval and quantification methods. / Catafau, A M ; Danus, M ; Bullich, S ; Llop, J ; Perich, J ; Cunningham, Vincent Joseph; Plaza, P ; Penengo, M M ; Eersels, J L H ; Squassante, L ; Ros, D ; Barbanoj, M .

In: Journal of Nuclear Medicine, Vol. 47, No. 6, 06.2006, p. 919-928.

Research output: Contribution to journalArticle

Catafau, AM, Danus, M, Bullich, S, Llop, J, Perich, J, Cunningham, VJ, Plaza, P, Penengo, MM, Eersels, JLH, Squassante, L, Ros, D & Barbanoj, M 2006, 'Characterization of the SPECT 5-HT2A receptor ligand I-123-R91150 in healthy volunteers: Part 1 - Pseudoequilibrium interval and quantification methods', Journal of Nuclear Medicine, vol. 47, no. 6, pp. 919-928.
Catafau, A M ; Danus, M ; Bullich, S ; Llop, J ; Perich, J ; Cunningham, Vincent Joseph ; Plaza, P ; Penengo, M M ; Eersels, J L H ; Squassante, L ; Ros, D ; Barbanoj, M . / Characterization of the SPECT 5-HT2A receptor ligand I-123-R91150 in healthy volunteers : Part 1 - Pseudoequilibrium interval and quantification methods. In: Journal of Nuclear Medicine. 2006 ; Vol. 47, No. 6. pp. 919-928.
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abstract = "With the aim of characterizing radioiodinated 4-amino-N-1[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2- methoxybenzamide (I-123-R91150) as a SPECT ligand for subtype 2A of the 5-hydroxytryptamine receptor (5-HT2A), tracer kinetic compartmental analyses were compared with the tissue ratio method (TR). The pseudoequilibrium interval after a single bolus injection was identified, and a reference database of specific uptake ratio (SUR) values was obtained. Within-scan and between-subject variability was also assessed. Methods: Nineteen healthy men (mean age SD, 24.4 +/- 3.3 y) were included and separated into 2 groups. Dynamic scans with venous blood sampling from 0 to 470 min after a single bolus injection of I-123-R91150 was completed for 7 of the 9 subjects included in group A, and in one of them compartmental modeling was performed with an arterial blood input function using 1-tissue-compartment (1TC) and 2-tissue-compartment (2TC) models. Binding potential (BP) using the simplified reference tissue model (SRTM) (BPSRTM) and SUR values using TR over time were also calculated. The 10 remaining subjects (group B) underwent a single scan at pseudoequilibrium with the aim of improving the precision of mean normal SUR estimates. Regions of interest in cortical regions and basal ganglia for specific uptake, and in cerebellum for nonspecific uptake, were manually drawn on each subject's MR images and translated to the corresponding SPECT slices after coregistration. Results: The 1TC model correlated well with the 2TC model (BP2TC = 1.04-BP1TC - 0.01, R-2 =0.98), and both methods correlated with BPSRTM and SUR with little bias (BP1TC = 1.10 BPSRTM + 0.03, R-2 = 0.98; BP2TC = 1.15 BPSRTM + 0.01 R-2 - 0.98; BPSRTM = 0.99 SURmean + 0.01, R-2 - 0.98). SUR values stabilized from 180 min after injection in most cortical regions, ranging from 0.51 +/- 0.10 in the orbitofrontal region to 0.27 +/- 0.09 in the parietal region. Within-scan and between-subject variability among regions ranged from 10{\%} to 14.8{\%}, and from 18.3{\%} to 35.4{\%}, respectively. Conclusion: I-123-R91150 distribution agrees with autoradiography results, showing highly specific binding in cortical regions. The correlations found among 1TC, 2TC, SRTM, and TR outcome measurements support the use of TR for quantification of 5-HT2A receptor binding with I-123-R91150 SPECT and a simple protocol avoiding arterial blood sampling and serial scanning over time.",
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author = "Catafau, {A M} and M Danus and S Bullich and J Llop and J Perich and Cunningham, {Vincent Joseph} and P Plaza and Penengo, {M M} and Eersels, {J L H} and L Squassante and D Ros and M Barbanoj",
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language = "English",
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journal = "Journal of Nuclear Medicine",
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TY - JOUR

T1 - Characterization of the SPECT 5-HT2A receptor ligand I-123-R91150 in healthy volunteers

T2 - Part 1 - Pseudoequilibrium interval and quantification methods

AU - Catafau, A M

AU - Danus, M

AU - Bullich, S

AU - Llop, J

AU - Perich, J

AU - Cunningham, Vincent Joseph

AU - Plaza, P

AU - Penengo, M M

AU - Eersels, J L H

AU - Squassante, L

AU - Ros, D

AU - Barbanoj, M

PY - 2006/6

Y1 - 2006/6

N2 - With the aim of characterizing radioiodinated 4-amino-N-1[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2- methoxybenzamide (I-123-R91150) as a SPECT ligand for subtype 2A of the 5-hydroxytryptamine receptor (5-HT2A), tracer kinetic compartmental analyses were compared with the tissue ratio method (TR). The pseudoequilibrium interval after a single bolus injection was identified, and a reference database of specific uptake ratio (SUR) values was obtained. Within-scan and between-subject variability was also assessed. Methods: Nineteen healthy men (mean age SD, 24.4 +/- 3.3 y) were included and separated into 2 groups. Dynamic scans with venous blood sampling from 0 to 470 min after a single bolus injection of I-123-R91150 was completed for 7 of the 9 subjects included in group A, and in one of them compartmental modeling was performed with an arterial blood input function using 1-tissue-compartment (1TC) and 2-tissue-compartment (2TC) models. Binding potential (BP) using the simplified reference tissue model (SRTM) (BPSRTM) and SUR values using TR over time were also calculated. The 10 remaining subjects (group B) underwent a single scan at pseudoequilibrium with the aim of improving the precision of mean normal SUR estimates. Regions of interest in cortical regions and basal ganglia for specific uptake, and in cerebellum for nonspecific uptake, were manually drawn on each subject's MR images and translated to the corresponding SPECT slices after coregistration. Results: The 1TC model correlated well with the 2TC model (BP2TC = 1.04-BP1TC - 0.01, R-2 =0.98), and both methods correlated with BPSRTM and SUR with little bias (BP1TC = 1.10 BPSRTM + 0.03, R-2 = 0.98; BP2TC = 1.15 BPSRTM + 0.01 R-2 - 0.98; BPSRTM = 0.99 SURmean + 0.01, R-2 - 0.98). SUR values stabilized from 180 min after injection in most cortical regions, ranging from 0.51 +/- 0.10 in the orbitofrontal region to 0.27 +/- 0.09 in the parietal region. Within-scan and between-subject variability among regions ranged from 10% to 14.8%, and from 18.3% to 35.4%, respectively. Conclusion: I-123-R91150 distribution agrees with autoradiography results, showing highly specific binding in cortical regions. The correlations found among 1TC, 2TC, SRTM, and TR outcome measurements support the use of TR for quantification of 5-HT2A receptor binding with I-123-R91150 SPECT and a simple protocol avoiding arterial blood sampling and serial scanning over time.

AB - With the aim of characterizing radioiodinated 4-amino-N-1[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2- methoxybenzamide (I-123-R91150) as a SPECT ligand for subtype 2A of the 5-hydroxytryptamine receptor (5-HT2A), tracer kinetic compartmental analyses were compared with the tissue ratio method (TR). The pseudoequilibrium interval after a single bolus injection was identified, and a reference database of specific uptake ratio (SUR) values was obtained. Within-scan and between-subject variability was also assessed. Methods: Nineteen healthy men (mean age SD, 24.4 +/- 3.3 y) were included and separated into 2 groups. Dynamic scans with venous blood sampling from 0 to 470 min after a single bolus injection of I-123-R91150 was completed for 7 of the 9 subjects included in group A, and in one of them compartmental modeling was performed with an arterial blood input function using 1-tissue-compartment (1TC) and 2-tissue-compartment (2TC) models. Binding potential (BP) using the simplified reference tissue model (SRTM) (BPSRTM) and SUR values using TR over time were also calculated. The 10 remaining subjects (group B) underwent a single scan at pseudoequilibrium with the aim of improving the precision of mean normal SUR estimates. Regions of interest in cortical regions and basal ganglia for specific uptake, and in cerebellum for nonspecific uptake, were manually drawn on each subject's MR images and translated to the corresponding SPECT slices after coregistration. Results: The 1TC model correlated well with the 2TC model (BP2TC = 1.04-BP1TC - 0.01, R-2 =0.98), and both methods correlated with BPSRTM and SUR with little bias (BP1TC = 1.10 BPSRTM + 0.03, R-2 = 0.98; BP2TC = 1.15 BPSRTM + 0.01 R-2 - 0.98; BPSRTM = 0.99 SURmean + 0.01, R-2 - 0.98). SUR values stabilized from 180 min after injection in most cortical regions, ranging from 0.51 +/- 0.10 in the orbitofrontal region to 0.27 +/- 0.09 in the parietal region. Within-scan and between-subject variability among regions ranged from 10% to 14.8%, and from 18.3% to 35.4%, respectively. Conclusion: I-123-R91150 distribution agrees with autoradiography results, showing highly specific binding in cortical regions. The correlations found among 1TC, 2TC, SRTM, and TR outcome measurements support the use of TR for quantification of 5-HT2A receptor binding with I-123-R91150 SPECT and a simple protocol avoiding arterial blood sampling and serial scanning over time.

KW - molecular imaging

KW - neurotransmission

KW - SPECT

KW - I-123-R91150

KW - 5-HT2A

KW - photon-emission-tomography

KW - human-brain

KW - binding index

KW - MDMA ecstasy

KW - test-retest

KW - I-123-5-I-R91150

KW - reproducibility

KW - displacement

KW - transporters

M3 - Article

VL - 47

SP - 919

EP - 928

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 6

ER -