Comparison of high specific activity (-) and (+)-6-[18F]fluoronorepinephrine and 6-[18F]fluorodopamine in baboons: heart uptake, metabolism and the effect of desipramine.
(-)-Norepinephrine is the principal neurotransmitter of the mammalian sympathetic nervous system and a major CNS neurotransmitter. The simple ring fluorinated derivatives of (-)- and (+)-norepinephrine [(-)- and (+)6-fluoronorepinephrine] and dopamine (6-fluorodopamine) have been labeled with 18F in high specific activity (2-5 Ci/mumol) and evaluated as tracers for (-)-norepinephrine. Comparative PET studies of (-) and (+)-6-[18F]fluoronorepinephrine [(-)-6-[18F]FNE and (+)-6-[18F]FNE] and 6-[18F]fluorodopamine (6-[18F]FDA) in the same baboon showed strikingly different kinetics in the heart. Analysis of plasma showed more rapid metabolism of 6-[18F]FDA with only 1%-2% of 18F remaining as parent tracer at 10 min after injection of 6-[18F]FDA, in contrast to 28% and 17% remaining after injection of (-) and (+)-6-[18F]FNE. No changes in vital signs were observed at any time during the study. Pretreatment with desipramine (0.5 mg/kg), a tricyclic antidepressant drug which interacts with a binding site associated with norepinephrine reuptake, markedly decreased cardiac uptake of 6-[18F]FDA and (-)-6-[18F]FNE. However, a greater blocking effect was observed for (-)-6-[18F]FNE. These studies show that (-) and (+)-6-[18F]FNE are similar to (-)- and (+)-norepinephrine in their patterns of metabolism and clearance in the heart and that (-)-6-[18F]FNE is a promising tracer for endogenous (-)-norepinephrine.
Ding
Y S
YS
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
Fowler
J S
JS
Dewey
S L
SL
Logan
J
J
Schlyer
D J
DJ
Gatley
S J
SJ
Volkow
N D
ND
King
P T
PT
Wolf
A P
AP
D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D004298:Dopamine / Q000031:analogs & derivatives*; D005260:Female; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000031:analogs & derivatives*; D010215:Papio; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; C029253:6-fluorodopamine; C024884:6-fluoronorepinephrine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine