Del Rosario R B, Jung Y W, Caraher J, Chakraborty P K, Wieland D M
Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
Nucl Med Biol. 1996 Jul;23(5):611-6. doi: 10.1016/0969-8051(96)00057-1.
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.
将（-）-[¹¹C]去氧肾上腺素（PHEN）的体内行为与结构相似但对单胺氧化酶（MAO）有抗性的类似物（-）-[¹¹C]-间羟基麻黄碱（HED）进行比较，HED是一种已确立的心脏神经元标志物。通过用¹¹CH₃I或CF₃SO₃¹¹CH₃对（-）-间章鱼胺进行直接甲基化，实现了PHEN的手性合成。这些合成方法产生的PHEN比活范围为500 - 1000 Ci/mmol，放射化学产率>50%（放化纯），对映体纯度为94 - 96%。生物分布研究表明，大鼠心脏对PHEN的初始摄取量约为HED的一半。注射PHEN后，放射性迅速从大鼠心脏排出，5至60分钟内有50%被清除。在此期间HED的清除率小于20%。通过地昔帕明阻断胺神经元转运体测定的心脏神经元选择性，PHEN为75 - 77%而HED为92 - 95%。环标记的（-）-[³H]去氧肾上腺素给出的组织与血液浓度比和心脏清除时间与PHEN非常相似。用MAO A抑制剂氯吉兰预处理的大鼠在15分钟和60分钟时心脏中的活性水平较高。在闭胸犬中用PHEN和HED进行的串联PET研究中，两种示踪剂都提供了出色的心脏图像。
