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Comparison of High Specific Activity (–) and (+)-6-[¹⁸F]Fluoronorepinephrine and 6-[¹⁸F]Fluorodopamine in Baboons: Heart Uptake, Metabolism and the Effect of Desipramine

Chemistry Department, Brookhaven National Laboratory, Upton, New York

Correspondence: For correspondence and reprints contact: Dr. Yu-Shin Ding, Department of Chemistry, Bldg. 555 - Lewis Rd., Brookhaven National Laboratory, Upton, NY 11973.

ABSTRACT

(–)-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/µmol) and evaluated as tracers for (–)-norepinephnne. 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.