L-[4-11C]aspartic acid: enzymic synthesis, myocardial uptake, and metabolism

Sterile, pyrogen-free L-[4-11C]aspartic acid was prepared from 11CO2 using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-[4-11C]aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of 11CO2 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of 11CO2. Positron-computed tomography imaging showed that the 11C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-[4-11C]aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-[4-11C]aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism.