title: Study of brain uptake and biodistribution of [11C]toluene in non-human primates and mice.
abstract: Inhalant abuse is a rapidly growing health problem particularly among adolescents. Yet we know little about the neural mechanisms underlying the abuse liability of inhalants, particularly when compared to other addictive drugs. Specifically, our understanding of the relationship between the regional brain phamacokinetics and features classically associated with drug reinforcement is lacking. Under the hypothesis that the abuse liability of toluene can be related to its pharmacokinetic properties and the pattern of regional brain uptake, we developed the methodology for radiolabeling and purifying [11C]toluene for use in PET studies. Here we report the regional brain distribution and kinetics of the widely abused solvent toluene in non-human primates and the whole body biodistribution in mice. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled toluene in non-human primates. Rapid uptake of radioactivity into striatal and frontal regions was followed by rapid clearance from the brain. Concurrent findings in rodents indicate similar radio-tracer kinetics, with excretion through kidneys and liver. Taken together, our data provides insight into pharmacokinetic features possibly associated with the abuse liability of toluene.
authors.affiliation: Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. madina@bnl.gov
authors.forename: M R
authors.initials: MR
authors.lastname: Gerasimov
authors.forename: R A
authors.initials: RA
authors.lastname: Ferrieri
authors.forename: W K
authors.initials: WK
authors.lastname: Schiffer
authors.forename: J
authors.initials: J
authors.lastname: Logan
authors.forename: S J
authors.initials: SJ
authors.lastname: Gatley
authors.forename: A N
authors.initials: AN
authors.lastname: Gifford
authors.forename: D A
authors.initials: DA
authors.lastname: Alexoff
authors.forename: D A
authors.initials: DA
authors.lastname: Marsteller
authors.forename: C
authors.initials: C
authors.lastname: Shea
authors.forename: V
authors.initials: V
authors.lastname: Garza
authors.forename: P
authors.initials: P
authors.lastname: Carter
authors.forename: P
authors.initials: P
authors.lastname: King
authors.forename: C R
authors.initials: CR
authors.lastname: Ashby
authors.forename: S
authors.initials: S
authors.lastname: Vitkun
authors.forename: S L
authors.initials: SL
authors.lastname: Dewey
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D007553:Isotope Labeling; D051379:Mice; D010215:Papio; D014018:Tissue Distribution; D014050:Toluene / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D014050:Toluene