SYNTHESIS AND PRELIMINARY EVALUATION OF [C-11]-(-)-PHENYLEPHRINE AS AFUNCTIONAL HEART NEURONAL PET AGENT

The in vivo behavior of (-)-[C-11]phenylephrine (PHEN) is compared wit h the structurally similar but monoamine oxidase (MAO)-resistant analo g (-)-[C-11]-m-hydroxyephedrine (HED), which is an established heart n euronal marker. The chiral synthesis of PHEN has been achieved by dire ct methylation of (-)-m-octopamine with either (CH3I)-C-11 Or (CF3SO3C H3)-C-11. These synthetic methods produced PHEN with a specific activi ty ranging from 500-1000 Ci/mmol, in a radiochemical yield of >50% (EO S) and with an enantiomeric purity of 94-96%. Biodistribution studies indicate the initial uptake of PHEN in rat heart is approximately half that of HED. Following PHEN injection, radioactivity egresses from th e rat heart rapidly, with 50% washout occurring from 5 to 60 min. LIED washout over this interval was less than 20%. The heart neuronal sele ctivity determined by desipramine blockade of the amine neuronal trans porter was 75-77% compared to 92-95% for LIED. Ring-labeled (-)-[H-3]p henylephrine gave tissue-to-blood concentration ratios and heart clear ance times very similar to PHEN. Rats pretreated with the MAO A inhibi tor clorgyline showed higher levels of activity in the heart: at 15 an d 60 min. Tandem PET studies with PHEN and HED in the closed-chest dog provided excellent heart images with both tracers.