POSITRON EMISSION TOMOGRAPHIC IMAGING OF CARDIAC SYMPATHETIC INNERVATION USING 6-[F-18]FLUORODOPAMINE - INITIAL FINDINGS IN HUMANS

Objectives. This study evaluated the safety, efficacy and validity of 6-[F-18]fluorodopamine positron emission tomographic scanning of cardi ac sympathetic innervation and function in humans. Methods. Positron e mission tomographic (PET) scans, arterial blood and urine were obtaine d after a 3-min intravenous infusion of 6-[F-18]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pret reatment with oral desipramine to inhibit neuronal uptake of catechola mines. Results. 6-[F-18]Fluorodopamine PET scanning visualized the lef t ventricular myocardium. Blood pressure increased slightly and transi ently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6 -[F-18]fluoradopamine. By 24 h after the injection, the main 6F-compou nd in urine was 6F-vanillylmandelic acid, a metabolite of 6F-norepinep hrine. Desipramine attenuated accumulation of myocardial 6-[F-18]fluor odopamine-derived radioactivity and plasma 6F-dihydroxyphenylacetic ac id. Conclusions. 6-[F-18]Fluorodopamine produces negligible hemodynami c effects and acceptable radiation exposure at doses that visualize th e left ventricular myocardium. Sympathetic nerves take up 6-[F-18]fluo rodopamine, which is translocated from the axoplasm into storage vesic les, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[F-18]fluorodopamine injection in humans is radiolabeling by 6-[F-18]fluorodopamine and 6-[F-18]fluorono repinephrine of vesicles in sympathetic terminals. 6-[F-18]Fluorodopam ine PET scanning provides a novel means for assessing sympathetic inne rvation and function noninvasively in the human heart.