Ding Y S, Fowler J S, Dewey S L, Logan J, Schlyer D J, Gatley S J, Volkow N D, King P T, Wolf A P
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
J Nucl Med. 1993 Apr;34(4):619-29.
(-)-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.
(-)-去甲肾上腺素是哺乳动物交感神经系统的主要神经递质以及中枢神经系统的一种主要神经递质。(-)-和(+)-去甲肾上腺素[(-)-和(+)-6-氟去甲肾上腺素]以及多巴胺(6-氟多巴胺)的简单环氟化衍生物已被高比活度(2 - 5 Ci/μmol)的18F标记，并被评估为(-)-去甲肾上腺素的示踪剂。在同一只狒狒身上对(-)-和(+)-6-[18F]氟去甲肾上腺素[(-)-6-[18F]FNE和(+)-6-[18F]FNE]以及6-[18F]氟多巴胺(6-[18F]FDA)进行的比较性正电子发射断层扫描(PET)研究显示，心脏中的动力学存在显著差异。血浆分析表明，6-[18F]FDA的代谢更快，注射6-[18F]FDA后10分钟，只有1% - 2%的18F作为母体示踪剂残留，相比之下，注射(-)-和(+)-6-[18F]FNE后分别有28%和17%残留。在研究过程中的任何时候均未观察到生命体征的变化。用与去甲肾上腺素再摄取相关的结合位点相互作用的三环抗抑郁药地昔帕明(0.5 mg/kg)预处理，可显著降低6-[18F]FDA和(-)-6-[18F]FNE的心脏摄取。然而，观察到(-)-啊6-[18F]FNE有更大的阻断作用。这些研究表明，(-)-和(+)-6-[18F]FNE在心脏中的代谢和清除模式与(-)-和(+)-去甲肾上腺素相似，并且(-)-6-[18F]FNE是一种有前景的内源性(-)-去甲肾上腺素示踪剂。
