title: Technetium-99m-N1-(2-mercapto-2-methylpropyl)-N2-(2-propargylthio-2- methylpropyl)-1,2-benzenediamine (T691): preclinical studies of a potential new tracer of regional cerebral perfusion.
abstract: We report in vitro and in vivo preclinical studies of a new cerebral blood flow tracer, [99mTc]N1-(2-mercapto-2-methyl-propyl)-N2-(2- propargylthio-2-methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in vitro chemical stability and accumulates regionally in the brain in a pattern consistent with that of cerebral blood flow. First-pass cerebral extraction determined with the use of the brain uptake index method in the rat was 0.76. Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68% and prolonged retention of 67% of the initially extracted activity. Autoradiographic studies in rats revealed a pattern characteristic of cerebral blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic imaging following systemic injection in the monkey revealed peak brain activity 1 to 2 min postinjection, without significant decline over 60 min. Chromatographic studies of brain as long as 60 min following systemic injection of [99mTc]T691 showed no evidence of tracer metabolism to account for its retention. Overall, [99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral perfusion.
authors.affiliation: Department of Internal Medicine (Division of Nuclear Medicine), University of Michigan, Ann Arbor.
authors.forename: S F
authors.initials: SF
authors.lastname: Taylor
authors.forename: K A
authors.initials: KA
authors.lastname: Frey
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: S M
authors.initials: SM
authors.lastname: Papadopoulos
authors.forename: N A
authors.initials: NA
authors.lastname: Petry
authors.forename: W L
authors.initials: WL
authors.lastname: Rogers
authors.forename: B J
authors.initials: BJ
authors.lastname: McBride
authors.forename: J M
authors.initials: JM
authors.lastname: Kerr
authors.forename: D E
authors.initials: DE
authors.lastname: Kuhl
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D008254:Macaca nemestrina; D015609:Organotechnetium Compounds / Q000737:chemistry; D010655:Phenylenediamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015609:Organotechnetium Compounds; D010655:Phenylenediamines; C077399:T 691