Metabolic fate of injected radiolabelled dopamine and 2-fluorodopamine in rats

Abstract

In evaluating positron-emitting analogs of dopamine (DA) as possible imaging agents for visualizing tissue sympathetic innervation and function, the metabolic fate of systemically injected [ 3H]-DA or [ 14C]-DA was compared with that of [ 3H]-2-fluoroDA in plasma and in sympathetically innervated tissues (left ventricle, spleen and salivary glands) of rats. By 60 min after the injection of [ 3H]-DA or [ 3H]-2-fluoroDA, concentrations of [ 3H]-DA, [ 3H]-2-fluoroDA, [ 3H]-norepinephrine ([ 3H]-NE) and [ 3H]-2-fluoroNE in tissue exceeded concentrations in plasma by up to several thousand-fold. Whereas most of the radioactivity in tissue was in catechols, radioactivity in plasma was due to O-methylated metabolites of DA, including homovanillic acid (HVA) and of NE, including nonnetanephrine (NMN) and methoxyhydroxphenylglycol (MHPG). Estimated ratios of tissue: blood radioactivity at 60 min after injection of [ 3H]-2-fluoroDA were 4.10 for the heart, 1.91 for the spleen and 2.10 for the salivary glands. Thepatterns of levels of catechol metabolites and analogs of HVA in plasma and effects of blockade of neuronal uptake with desipramine suggested that [ 3H]-2-fluoroDA was not as efficiently removed by neuronal uptake and not as efficiently β-hydroxylated as the non-fluorinated compound. Concurrent administration of [ 3H]-DA and large amounts of non-radioactive 2-fluoroDA did not substantially alter the pattern of metabolites of [ 3H]-DA in plasma. After injection of [ 18F]-fluoroDA, visualization of sympathetic innervation of tissue should be feasible by positron emission tomography.