Neuronal mapping of the heart with 6-[18F]fluorometaraminol.

The false neurotransmitter metaraminol labeled with fluorine-18 has been used to noninvasively assess regional adrenergic nerve density in the canine heart. Intravenous administration of 6-[18F]fluorometaraminol (FMR) results in high, selective accumulation of radioactivity in the heart; drug blocking studies with desipramine and reserpine confirm the neuronal locus of FMR. Iodine-125 labeled metaraminol, however, shows no selective accumulation in the canine heart. Positron emission tomography (PET) analyses with FMR of closed-chest dogs bearing left ventricular neuronal defects clearly delineate the region of neuronal impairment; blood perfusion in the left ventricle wall was homogeneous as determined by [13N]NH3 tomograms. The accumulation of FMR in regionally denervated dog heart correlates closely (r = 0.88) with endogenous norepinephrine concentrations. PET-generated 18F time-activity curves demonstrate marked kinetic differences between normal and denervated myocardium. FMR/PET analysis could be used to assess the heterogeneity of sympathetic innervation in human heart disease contingent on the development of FMR with sufficiently high specific activity to clearly avoid pressor activity.

Metabolic fate of the heart agent [18F]6-fluorometaraminol.

Studies were performed to determine whether [18F]6-fluorometaraminol (18F-FMR), a new neuronal heart radiopharmaceutical, is metabolized in vivo and if the metabolites are taken up in heart. Rat, dog, baboon and guinea pig were injected with 18F-FMR and tissue samples were analyzed for metabolites by HPLC. Liver contained the most metabolites of the tissues studied with 25-90% of the radioactivity present as metabolites at 1 h in all the species studied. While metabolites of 18F-FMR are found in blood, no significant accumulation of these metabolites is found in heart (less than or equal to 0.3%) 1 h after i.v. administration in any species except rat. These studies suggest that 18F-FMR is a suitable agent for quantitative imaging of the heart by positron emission tomography.

6-[18F]fluorometaraminol: a radiotracer for in vivo mapping of adrenergic nerves of the heart.

The false neurotransmitter metaraminol has been 18F labeled and evaluated as a possible heart imaging agent on the basis of its selective accumulation in adrenergic nerves. Reaction of 6-(acetoxymercurio)-N-t-BOC-metaraminol with acetyl hypofluorite followed by removal of the BOC group provides a regiospecific synthesis of 6-fluorometaraminol (4). Use of acetyl hypo[18F]fluorite gives [18F]-4 in 60 min in 20-42% radiochemical yield. Systemic blockade of the neuronal uptake-1 carrier with desmethylimipramine or systemic destruction of the adrenergic nerves with 6-hydroxydopamine lowers [18F]-4 accumulation greater than or equal to 85% in all four regions of the rat heart. These preliminary findings suggest that [18F]-4 could be used to assess neuronal damage in various heart diseases by positron emission tomography.