High specific radioactivity (1R,2S)-4-[F-18]fluorometaraminol: A PET radiotracer for mapping sympathetic nerves of the heart

The radiolabeled catecholamine analogue (1R,2S)-6-[F-18]fluorometaraminol ( 6-[F-18]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympat hetic nerves in dog heart. 6-[F-18]FMR could be only synthesized with low s pecific radioactivity, which precluded its use in human subjects. We have r ecently prepared (1R,2S)-4-[F-18]fluorometaraminol (4-[F-18]FMR), a new flu oro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/m u mol). In the present study, we demonstrate in rats that 4-[F-18]FMR posse sses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[F-18]FMR. When compared with control animals, an 80% and 76% reducti on in myocardial uptake was observed in animals pretreated with desipramine tan inhibitor of the neuronal norepinephrine transporter) and with reserpi ne (a blocker of the vesicular storage of monoamines), respectively. The en tire radioactivity in rat myocardium represented unmetabolized parent trace r as determined by-high performance liquid chromatography analysis of tissu e extracts. In dogs, myocardial kinetics of 4-[F-18]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac r etention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half life of 4-[F-18]FMR by 90% compared with control, Moreover, an infusion of tyra mine caused a rapid decline of radioactivity in the heart. This demonstrate s that 4-[F-18]FMR specifically visualizes sympathetic neurons in dog heart . High specific radioactivity 4-[F-18]FMR is a promising alternative to 6-[ F-18]FMR for myocardial neuronal mapping with PET in humans. NUCL MED BIOL 27;3:233-238, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.