Biomaterial Database

Modeling of fluorine-18-6-fluoro-L-Dopa in humans. 1996

L Wahl, and C Nahmias

Department of Nuclear Medicine, McMaster University Medical Centre Hamilton, Ontario, Canada.

Fluorine-18-6-fluoro-L-Dopa (F-Dopa) has been used successfully to evaluate striatal dopaminergic function in humans. The kinetic analysis of F-Dopa studies, however, is confounded by the presence of [18F]6-fluoro-3-O-methyl-L-Dopa (OMFD), the major metabolite of F-Dopa formed in the periphery that crosses the blood-brain barrier. We present results of compartmental analysis in subjects in whom we independently measured the kinetics of OMFD in the blood and striatum, and used this knowledge to solve for the kinetics of F-Dopa. METHODS The kinetics of F-Dopa in striatum were measured with PET from 0 to 150 min after an intravenous bolus injection of tracer in four normal subjects and two patients suffering from Parkinson's disease. On a separate occasion, the kinetics of OMFD were determined in the plasma and striatum of the same individuals. The measured OMFD kinetics of each individual allowed us to reduce the number of compartments and rate constants which have to be solved for any compartmental analysis of the kinetics of F-Dopa. RESULTS A two-compartmental, three rate-constant model was sufficient to describe the time course of F-Dopa and its metabolites in the striatum. The rate constant (k21) representing the decarboxylation rate of F-Dopa was 0.0124 min-1 in the normal subjects, and 0.0043 min-1 in the parkinsonian patients. CONCLUSIONS The data do not support the need to include a fourth rate constant representing the egress of F-Dopamine and its metabolites. The forward transport rates for F-Dopa and OMFD from plasma to striatum are very similar in humans.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010300	Parkinson Disease	A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D001812	Blood-Brain Barrier	Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.	Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D003342	Corpus Striatum	Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.	Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004295	Dihydroxyphenylalanine	A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.	Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005462	Fluorine Radioisotopes	Unstable isotopes of fluorine that decay or disintegrate emitting radiation. F atoms with atomic weights 17, 18, and 20-22 are radioactive fluorine isotopes.	Radioisotopes, Fluorine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man