The purpose of this study was to investigate the pharmacologic characterist
ics of TRODAT-1 (2 beta-((N,N'-bis(2-mercaproethyl)ethylene diamino)methyl)
, 3 beta-(4-chlorophenyl)tropane) labeled with [Tc-99m] as an imaging agent
for dopamine transporter (DAT). Radiochemical purity of [Tc-99m]TRODAT-1 w
as 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 i
n rats, rabbits, and normal and hemi-Parkinsonian model monkeys. Biodistrib
ution 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 radio
activity was excreted by the hepatobiliary system. Blood clearance kinetics
was performed in rabbits, and the initial half-life of 1.18 min and late h
alf-life of 367.8 min were obtained. Brain single photon emission computed
tomography imaging studies in normal monkeys showed the ratios of ST/CB upt
ake 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-Parkinsoni
an model monkeys also displayed the expected selectivity, the highest uptak
e bring observed in the basal ganglia area of the normal side. Thereby, it
is suggested that [Tc-99m]TRODAT-1 is a safe and useful imaging agent for l
ocalization of the presynaptic DAT in the brain. NUCL MED BIOL 27;1:69-75,
2000. (C) 2000 Elsevier Science Inc. All rights reserved.