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.
Wieland
D M
DM
Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552.
Rosenspire
K C
KC
Hutchins
G D
GD
Van Dort
M
M
Rothley
J M
JM
Mislankar
S G
SG
Lee
H T
HT
Massin
C C
CC
Gildersleeve
D L
DL
Sherman
P S
PS
D000818:Animals; D004285:Dogs; D005260:Female; D005462:Fluorine Radioisotopes; D006321:Heart / Q000294:innervation*; D008680:Metaraminol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D009638:Norepinephrine / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014316:Tritium
D005462:Fluorine Radioisotopes; D014316:Tritium; C054817:6-fluorometaraminol; D008680:Metaraminol; D009638:Norepinephrine