title: The preclinical pharmacologic study of dopamine transporter imaging agent [99mTc]TRODAT-1.
abstract: The purpose of this study was to investigate the pharmacologic characteristics of TRODAT-1 (2beta-((N,N'-bis(2-mercaptoethyl)ethylene diamino)methyl), 3beta-(4-chlorophenyl)tropane) labeled with [99mTc] as an imaging agent for dopamine transporter (DAT). Radiochemical purity of [99mTc]TRODAT-1 was over 90%. The partition coefficients in octanol and buffer were 2.12 and 2.19 at pH 7.0 and 7.4, respectively. Animal studies have been performed in rats, rabbits, and normal and hemi-Parkinsonian model monkeys. Biodistribution displayed moderate uptake in rat brain (0.28 %ID/organ at 2 min) and the striatal uptake was 0.193, 0.142, and 0.136 %ID/g at 2, 60, and 120 min, respectively. The ratios of striatal/cerebellar (ST/CB) uptake were 2.4, 4.45, and 2.45 %ID/g at 60, 120, and 240 min, respectively. The major radioactivity was excreted by the hepatobiliary system. Blood clearance kinetics was performed in rabbits, and the initial half-life of 1.18 min and late half-life of 367.8 min were obtained. Brain single photon emission computed tomography imaging studies in normal monkeys showed the ratios of ST/CB uptake were 1.56-2.0 %ID/g and indicated that both uptake and retention in the striatal area were associated with the DAT. The imaging of hemi-Parkinsonian model monkeys also displayed the expected selectivity, the highest uptake being observed in the basal ganglia area of the normal side. Thereby, it is suggested that [99mTc]TRODAT-1 is a safe and useful imaging agent for localization of the presynaptic DAT in the brain.
authors.affiliation: National Laboratory of Nuclear Medicine, Wuxi, Jiangsu, China. jsinm@public1.wx.js.cn
authors.forename: P
authors.initials: P
authors.lastname: Fang
authors.forename: C Y
authors.initials: CY
authors.lastname: Wu
authors.forename: Z G
authors.initials: ZG
authors.lastname: Liu
authors.forename: W X
authors.initials: WX
authors.lastname: Wan
authors.forename: T S
authors.initials: TS
authors.lastname: Wang
authors.forename: S D
authors.initials: SD
authors.lastname: Chen
authors.forename: Z P
authors.initials: ZP
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D050483:Dopamine Plasma Membrane Transport Proteins; D004355:Drug Stability; D000882:Haplorhini; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008657:Metabolic Clearance Rate; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000009:adverse effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013667:Technetium; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds; C493216:Slc6a3 protein, rat; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; D013667:Technetium