Synthesis and preliminary evaluation of [C-11]-(-)-phenylephrine as a functional heart neuronal PET agent
Synthesis and preliminary evaluation of [C-11]-(-)-phenylephrine as a functional heart neuronal PET agent
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DOI：
10.1016/0969-8051(96)00057-1
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发表时间：
1996-07-01
影响因子：
3.1
通讯作者：
Wieland, DM
中科院分区：
文献类型：
--
作者：
DelRosario, RB;Jung, YW;Wieland, DM
将（-）-[C-11]苯麻黄碱（PHEN）的体内行为与结构相似但具有单胺氧化酶（MAO）抗性的类似物（-）-[C-11]-间羟基麻黄碱（HED）进行比较，后者是一种已确立的心脏神经元标记物。用（CH_3 I）-C-11或（CF_3SO_3CH_3）-C-11直接甲基化（-）-m-章鱼胺，合成了对映体PHEN。这些合成方法产生的PHEN具有500-1000 Ci/mmol的比活度，放射化学产率>50%（EOS），对映体纯度为94- 96%。生物分布研究表明，PHEN在大鼠心脏中的初始摄取约为HED的一半。注射PHEN后，放射性迅速从大鼠心脏流出，从5至60分钟发生50%的洗脱。在此期间的LIED洗脱小于20%。通过地昔帕明阻断胺神经元转运蛋白测定的心脏神经元选择性为75-77%，而LIED为92-95%。环标记的（-）-[H-3] phenylethyl的组织-血液浓度比和心脏清除时间非常相似的PHEN。用单胺氧化酶A抑制剂氯吉林预处理的大鼠在心脏中表现出更高水平的活动：在15和60分钟。在闭胸犬中用PHEN和HED进行的串联PET研究提供了两种示踪剂的出色心脏图像。
The in vivo behavior of (-)-[C-11]phenylephrine (PHEN) is compared with the structurally similar but monoamine oxidase (MAO)-resistant analog (-)-[C-11]-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 (CH3I)-C-11 Or (CF3SO3CH3)-C-11. 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. LIED 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 LIED. Ring-labeled (-)-[H-3]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.