title: Distribution volume of 3-O-methyl-6.
abstract: The distribution volume (DV) of 6-[F-18]fluoro-L-DOPA (FDOPA) in the cerebellum recently has been linked using positron emission tomography (PET) to plasma large neutral amino acid (LNAA) concentrations in monkeys. In this article the authors provide additional experimental support for this relation by directly measuring the DV as the steady-state tissue to plasma radioactivity ratio in rats using a labeled LNAA analog 3-O-methyl-6-[F-18]FDOPA (OMFD), a compound that has no known specific enzyme or receptor interactions in brain tissue. The measured DV for OMFD (tissue OMFD concentration/plasma OMFD concentration) was found to be inversely related to plasma LNAA concentrations. The relation (DV = 1.5-0.00094*[LNAA], R--2 = 0.79) resulted in an 8% DV decrease per 100 nmol/mL plasma LNAA increase within the observed range of 330 to 510 nmol/mL. This was similar to recent noninvasive observations with FDOPA PET in vervet monkeys and with 6-[F-18]Fluoro-m-tyrosine PET in squirrel monkeys. The OMFD striatum to cerebellum (Str/Cb) ratio was greater than 1.0 for all measurements, averaging 1.09 +/- 0.04, and was approximately equal to the Str/Cb LNAA ratio of 1.12 +/- 0.05. This current study verifies the variation of DV of OMFD or FDOPA as a function of plasma LNAA concentrations and suggests the possibility of using OMFD for measuring cerebral LNAA noninvasively with PET.
authors.affiliation: Department of Medical and Molecular Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-6948, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Stout
authors.forename: S C
authors.initials: SC
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Namavari
authors.forename: N
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: R E
authors.initials: RE
authors.lastname: Yee
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D021542:Amino Acids, Neutral / Q000032:analysis / Q000097:blood; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002531:Cerebellum / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism; D003342:Corpus Striatum / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D021542:Amino Acids, Neutral; C055151:3-O-methyl-6-fluoro-dopa; D004295:Dihydroxyphenylalanine