Synthesis and preliminary evaluation of [11C]-(-)-phenylephrine as a functional heart neuronal PET agent.
The in vivo behavior of (-)-[11C]phenylephrine (PHEN) is compared with the structurally similar but monoamine oxidase (MAO)-resistant analog (-)-[11C]-m-hydroxyephedrine (HED), which is an established heart neuronal marker. The chiral synthesis of PHEN has been achieved by direct methylation of (-)-m-octopamine with either 11CH3I or CF3SO311CH3. These synthetic methods produced PHEN with a specific activity ranging from 500-1000 Ci/mmol, in a radiochemical yield of > 50% (EOS) 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 the rat heart rapidly, with 50% washout occurring from 5 to 60 min. HED washout over this interval was less than 20%. The heart neuronal selectivity determined by desipramine blockade of the amine neuronal transporter was 75-77% compared to 92-95% for HED. Ring-labeled (-)-[3H]phenylephrine gave tissue-to-blood concentration ratios and heart clearance times very similar to PHEN. Rats pretreated with the MAO A inhibitor clorgyline showed higher levels of activity in the heart at 15 and 60 min. Tandem PET studies with PHEN and HED in the closed-chest dog provided excellent heart images with both tracers.
Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
R B
RB
Del Rosario
Y W
YW
Jung
J
J
Caraher
P K
PK
Chakraborty
D M
DM
Wieland
D000818:Animals; D002250:Carbon Radioisotopes; D003010:Clorgyline / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D009206:Myocardium / Q000378:metabolism; D010656:Phenylephrine / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; D010656:Phenylephrine; D003010:Clorgyline