Graphical analysis of 6-fluoro-L-dopa trapping

Effect of inhibition of catechol-O-methyltransferase

J. E. Holden, D. Doudet, C. J. Endres, G. L Y Chan, K. S. Morrison, F. J G Vingerhoets, B. J. Snow, B. D. Pate, V. Sossi, K. R. Buckley, T. J. Ruth

Research output: Contribution to journalArticle

Abstract

Graphical methods to analyze tracer time-course data allow reliable quantitation of the rate of incorporation of tracer from plasma into a 'trapped' kinetic component, even when the details of the kinetic model are unknown. Applications of the method over long time periods often expose the slow reversibility of the trapping process. In the extended graphical method, both trapping rate and a presumed first-order loss rate constant are estimated simultaneously from the time-course data. Methods: We applied the extended graphical method to 6-fluoro-L-dopa (6-FD), simultaneously estimating the rate of uptake (K1) and the rate constant for loss from the trapped component (k(loss)) in a single fitting procedure. We applied this approach to study the effects of two catechol-O-methyl-transferase inhibitors on the kinetics of 6-FD in cynomolgus monkeys. Results: Inhibition of peripheral O-methylation with either inhibitor, confirmed by high-performance liquid chromatography analysis of labeled compounds in arterial plasma, had no significant effect on K1, in agreement with previously reported studies. In contrast, tolcapone, a catechol-O-methyl-transferase inhibitor, having central effects in addition to peripheral effects at the dosage used, decreased k(loss) by 40% from control values (p

Original languageEnglish (US)
Pages (from-to)1568-1574
Number of pages7
JournalJournal of Nuclear Medicine
Volume38
Issue number10
StatePublished - Oct 1997
Externally publishedYes

Fingerprint

Catechol O-Methyltransferase
Levodopa
Guaiacol
Transferases
Macaca fascicularis
Methylation
High Pressure Liquid Chromatography

Keywords

  • 6-fluoro-dopa
  • COMT inhibition
  • Extended graphical method
  • PET
  • Reversible trapping

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Holden, J. E., Doudet, D., Endres, C. J., Chan, G. L. Y., Morrison, K. S., Vingerhoets, F. J. G., ... Ruth, T. J. (1997). Graphical analysis of 6-fluoro-L-dopa trapping: Effect of inhibition of catechol-O-methyltransferase. Journal of Nuclear Medicine, 38(10), 1568-1574.

Graphical analysis of 6-fluoro-L-dopa trapping : Effect of inhibition of catechol-O-methyltransferase. / Holden, J. E.; Doudet, D.; Endres, C. J.; Chan, G. L Y; Morrison, K. S.; Vingerhoets, F. J G; Snow, B. J.; Pate, B. D.; Sossi, V.; Buckley, K. R.; Ruth, T. J.

In: Journal of Nuclear Medicine, Vol. 38, No. 10, 10.1997, p. 1568-1574.

Research output: Contribution to journalArticle

Holden, JE, Doudet, D, Endres, CJ, Chan, GLY, Morrison, KS, Vingerhoets, FJG, Snow, BJ, Pate, BD, Sossi, V, Buckley, KR & Ruth, TJ 1997, 'Graphical analysis of 6-fluoro-L-dopa trapping: Effect of inhibition of catechol-O-methyltransferase', Journal of Nuclear Medicine, vol. 38, no. 10, pp. 1568-1574.
Holden JE, Doudet D, Endres CJ, Chan GLY, Morrison KS, Vingerhoets FJG et al. Graphical analysis of 6-fluoro-L-dopa trapping: Effect of inhibition of catechol-O-methyltransferase. Journal of Nuclear Medicine. 1997 Oct;38(10):1568-1574.
Holden, J. E. ; Doudet, D. ; Endres, C. J. ; Chan, G. L Y ; Morrison, K. S. ; Vingerhoets, F. J G ; Snow, B. J. ; Pate, B. D. ; Sossi, V. ; Buckley, K. R. ; Ruth, T. J. / Graphical analysis of 6-fluoro-L-dopa trapping : Effect of inhibition of catechol-O-methyltransferase. In: Journal of Nuclear Medicine. 1997 ; Vol. 38, No. 10. pp. 1568-1574.
@article{9a99109b5c9a4607971c0f195c822414,
title = "Graphical analysis of 6-fluoro-L-dopa trapping: Effect of inhibition of catechol-O-methyltransferase",
abstract = "Graphical methods to analyze tracer time-course data allow reliable quantitation of the rate of incorporation of tracer from plasma into a 'trapped' kinetic component, even when the details of the kinetic model are unknown. Applications of the method over long time periods often expose the slow reversibility of the trapping process. In the extended graphical method, both trapping rate and a presumed first-order loss rate constant are estimated simultaneously from the time-course data. Methods: We applied the extended graphical method to 6-fluoro-L-dopa (6-FD), simultaneously estimating the rate of uptake (K1) and the rate constant for loss from the trapped component (k(loss)) in a single fitting procedure. We applied this approach to study the effects of two catechol-O-methyl-transferase inhibitors on the kinetics of 6-FD in cynomolgus monkeys. Results: Inhibition of peripheral O-methylation with either inhibitor, confirmed by high-performance liquid chromatography analysis of labeled compounds in arterial plasma, had no significant effect on K1, in agreement with previously reported studies. In contrast, tolcapone, a catechol-O-methyl-transferase inhibitor, having central effects in addition to peripheral effects at the dosage used, decreased k(loss) by 40{\%} from control values (p",
keywords = "6-fluoro-dopa, COMT inhibition, Extended graphical method, PET, Reversible trapping",
author = "Holden, {J. E.} and D. Doudet and Endres, {C. J.} and Chan, {G. L Y} and Morrison, {K. S.} and Vingerhoets, {F. J G} and Snow, {B. J.} and Pate, {B. D.} and V. Sossi and Buckley, {K. R.} and Ruth, {T. J.}",
year = "1997",
month = "10",
language = "English (US)",
volume = "38",
pages = "1568--1574",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "10",

}

TY - JOUR

T1 - Graphical analysis of 6-fluoro-L-dopa trapping

T2 - Effect of inhibition of catechol-O-methyltransferase

AU - Holden, J. E.

AU - Doudet, D.

AU - Endres, C. J.

AU - Chan, G. L Y

AU - Morrison, K. S.

AU - Vingerhoets, F. J G

AU - Snow, B. J.

AU - Pate, B. D.

AU - Sossi, V.

AU - Buckley, K. R.

AU - Ruth, T. J.

PY - 1997/10

Y1 - 1997/10

N2 - Graphical methods to analyze tracer time-course data allow reliable quantitation of the rate of incorporation of tracer from plasma into a 'trapped' kinetic component, even when the details of the kinetic model are unknown. Applications of the method over long time periods often expose the slow reversibility of the trapping process. In the extended graphical method, both trapping rate and a presumed first-order loss rate constant are estimated simultaneously from the time-course data. Methods: We applied the extended graphical method to 6-fluoro-L-dopa (6-FD), simultaneously estimating the rate of uptake (K1) and the rate constant for loss from the trapped component (k(loss)) in a single fitting procedure. We applied this approach to study the effects of two catechol-O-methyl-transferase inhibitors on the kinetics of 6-FD in cynomolgus monkeys. Results: Inhibition of peripheral O-methylation with either inhibitor, confirmed by high-performance liquid chromatography analysis of labeled compounds in arterial plasma, had no significant effect on K1, in agreement with previously reported studies. In contrast, tolcapone, a catechol-O-methyl-transferase inhibitor, having central effects in addition to peripheral effects at the dosage used, decreased k(loss) by 40% from control values (p

AB - Graphical methods to analyze tracer time-course data allow reliable quantitation of the rate of incorporation of tracer from plasma into a 'trapped' kinetic component, even when the details of the kinetic model are unknown. Applications of the method over long time periods often expose the slow reversibility of the trapping process. In the extended graphical method, both trapping rate and a presumed first-order loss rate constant are estimated simultaneously from the time-course data. Methods: We applied the extended graphical method to 6-fluoro-L-dopa (6-FD), simultaneously estimating the rate of uptake (K1) and the rate constant for loss from the trapped component (k(loss)) in a single fitting procedure. We applied this approach to study the effects of two catechol-O-methyl-transferase inhibitors on the kinetics of 6-FD in cynomolgus monkeys. Results: Inhibition of peripheral O-methylation with either inhibitor, confirmed by high-performance liquid chromatography analysis of labeled compounds in arterial plasma, had no significant effect on K1, in agreement with previously reported studies. In contrast, tolcapone, a catechol-O-methyl-transferase inhibitor, having central effects in addition to peripheral effects at the dosage used, decreased k(loss) by 40% from control values (p

KW - 6-fluoro-dopa

KW - COMT inhibition

KW - Extended graphical method

KW - PET

KW - Reversible trapping

UR - http://www.scopus.com/inward/record.url?scp=9844233705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9844233705&partnerID=8YFLogxK

M3 - Article

VL - 38

SP - 1568

EP - 1574

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 10

ER -