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Fluorodopa positron emission tomography with an inhibitor of catechol-O-methyltransferase: effect of the plasma 3-O-methyldopa fraction on data analysis.
J Cereb Blood Flow Metab. 1996 Sep; 16(5):854-63.JC

Abstract

Flurodopa (FDOPA) is an analogue of L-di-hydroxyphenylalanine (L-dopa) used to assess the nigrostriatal dopamine system in vivo with positron emission tomography (PET). However, FDOPA/PET quantitation is complicated by the presence of the 3-O-methyl-FDOPA (3OMFD) fraction in brain and plasma. Pretreatment with entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal situation to evaluate the contribution of the plasma 3OMFD fraction in several kinetic models of FDOPA uptake. We performed FDOPA/PET with and without the OR-611 preadministration in six Parkinson's disease (PD) patients. We measured the time-course of the plasma FDOPA and 3OMFD fractions using high-pressure liquid chromatography (HPLC). We calculated striato-occipital ratios (SOR), and estimated the striatal FDOPA uptake rate constant graphically using the plasma FDOPA and occipital tissue time activity curves (KiFD and KiOCC, respectively). We also estimated striatal dopa decarboxylase (DDC) activity (k3D) using a model incorporating independent measurements of 3OMFD transport kinetic rate constants. With the preadministration of OR-611, the pharmacological efficiency in plasma was prolonged significantly (21.1-37.7%; p < 0.01). We also observed significant mean elevations in SOR and KiOCC by 21.8 and 53.5%, respectively (p < 0.05). KiFD and k3D did not show significant change. We conclude that OR-611 prolongs the circulation time of FDOPA in the plasma but does not alter rate constants for striatal FDOPA uptake or decarboxylation.

Authors+Show Affiliations

Department of Neurology, North Shore University Hospital/Cornell, University Medical College, Manhasset, New York 11030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8784230

Citation

Ishikawa, T, et al. "Fluorodopa Positron Emission Tomography With an Inhibitor of catechol-O-methyltransferase: Effect of the Plasma 3-O-methyldopa Fraction On Data Analysis." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 16, no. 5, 1996, pp. 854-63.
Ishikawa T, Dhawan V, Chaly T, et al. Fluorodopa positron emission tomography with an inhibitor of catechol-O-methyltransferase: effect of the plasma 3-O-methyldopa fraction on data analysis. J Cereb Blood Flow Metab. 1996;16(5):854-63.
Ishikawa, T., Dhawan, V., Chaly, T., Robeson, W., Belakhlef, A., Mandel, F., Dahl, R., Margouleff, C., & Eidelberg, D. (1996). Fluorodopa positron emission tomography with an inhibitor of catechol-O-methyltransferase: effect of the plasma 3-O-methyldopa fraction on data analysis. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 16(5), 854-63.
Ishikawa T, et al. Fluorodopa Positron Emission Tomography With an Inhibitor of catechol-O-methyltransferase: Effect of the Plasma 3-O-methyldopa Fraction On Data Analysis. J Cereb Blood Flow Metab. 1996;16(5):854-63. PubMed PMID: 8784230.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluorodopa positron emission tomography with an inhibitor of catechol-O-methyltransferase: effect of the plasma 3-O-methyldopa fraction on data analysis. AU - Ishikawa,T, AU - Dhawan,V, AU - Chaly,T, AU - Robeson,W, AU - Belakhlef,A, AU - Mandel,F, AU - Dahl,R, AU - Margouleff,C, AU - Eidelberg,D, PY - 1996/9/1/pubmed PY - 1996/9/1/medline PY - 1996/9/1/entrez SP - 854 EP - 63 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 16 IS - 5 N2 - Flurodopa (FDOPA) is an analogue of L-di-hydroxyphenylalanine (L-dopa) used to assess the nigrostriatal dopamine system in vivo with positron emission tomography (PET). However, FDOPA/PET quantitation is complicated by the presence of the 3-O-methyl-FDOPA (3OMFD) fraction in brain and plasma. Pretreatment with entacapone (OR-611), a peripheral catechol O-methyl-transferase (COMT) inhibitor, greatly reduces the plasma 3OMFD fraction and provides an ideal situation to evaluate the contribution of the plasma 3OMFD fraction in several kinetic models of FDOPA uptake. We performed FDOPA/PET with and without the OR-611 preadministration in six Parkinson's disease (PD) patients. We measured the time-course of the plasma FDOPA and 3OMFD fractions using high-pressure liquid chromatography (HPLC). We calculated striato-occipital ratios (SOR), and estimated the striatal FDOPA uptake rate constant graphically using the plasma FDOPA and occipital tissue time activity curves (KiFD and KiOCC, respectively). We also estimated striatal dopa decarboxylase (DDC) activity (k3D) using a model incorporating independent measurements of 3OMFD transport kinetic rate constants. With the preadministration of OR-611, the pharmacological efficiency in plasma was prolonged significantly (21.1-37.7%; p < 0.01). We also observed significant mean elevations in SOR and KiOCC by 21.8 and 53.5%, respectively (p < 0.05). KiFD and k3D did not show significant change. We conclude that OR-611 prolongs the circulation time of FDOPA in the plasma but does not alter rate constants for striatal FDOPA uptake or decarboxylation. SN - 0271-678X UR - https://www.unboundmedicine.com/medline/citation/8784230/Fluorodopa_positron_emission_tomography_with_an_inhibitor_of_catechol_O_methyltransferase:_effect_of_the_plasma_3_O_methyldopa_fraction_on_data_analysis_ L2 - https://journals.sagepub.com/doi/10.1097/00004647-199609000-00010?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -