Structure dependence of long-chain [18F]fluorothia fatty acids as myocardial fatty acid oxidation probes.
Structure dependence of long-chain [18F]fluorothia fatty acids as myocardial fatty acid oxidation probes.
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长链[18F]氟硫脂肪酸作为心肌脂肪酸氧化探针的结构依赖性。
DOI：
10.1021/jm301345v
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发表时间：
2012
影响因子：
7.3
通讯作者：
DeGrado,TimothyR
中科院分区：
文献类型：
--
作者：
Pandey,MukeshK;Belanger,AnthonyP;Wang,Shuyan;DeGrado,TimothyR
区域脂肪酸氧化（FAO）率的体内成像将具有相当大的潜力，用于评估哺乳动物疾病。我们已经合成和evaluated 18F-标记的硫杂脂肪酸类似物作为代谢捕获的FAO探针，以了解链长，不饱和度，和放置的硫杂取代基对心肌摄取和保留的影响。18-[18 F]氟-4-硫杂-（9 Z）-十八碳-9-烯酸（3）显示出良好的心脏/背景放射性浓度比，沿着在心脏和肝脏中的保留最高。用CPT-1抑制剂波卡预处理大鼠，导致心肌摄取16-[18 F]氟-4-硫代十六烷酸减少>80%（2）和3，表明对FAO具有高度特异性。相比之下，18-[18F]氟-4-硫代十八烷酸（4）显示心肌摄取显著降低，对波卡的反应减弱。18-[18F]氟-6-硫代十八烷酸（5）显示中度心肌摄取，心肌摄取对波卡不敏感。结果表明18F标记的硫代脂肪酸的结构和摄取之间的关系，以及它们作为FAO探针在各种组织中的实用性。
In vivo imaging of regional fatty acid oxidation (FAO) rates would have considerable potential for evaluation of mammalian diseases. We have synthesized and evaluated18F-labeled thia fatty acid analogues as metabolically trapped FAO probes to understand the effect of chain length, degree of unsaturation, and placement of the thia substituent on myocardial uptake and retention. 18-[18F]Fluoro-4-thia-(9Z)-octadec-9-enoic acid (3) showed excellent heart/background radioactivity concentration ratios along with highest retention in heart and liver. Pretreatment of rats with the CPT-1 inhibitor, POCA, caused >80% reduction in myocardial uptake of 16-[18F]fluoro-4-thiahexadecanoic acid (2) and3, indicating high specificity for FAO. In contrast, 18-[18F]fluoro-4-thiaoctadecanoic acid (4) showed dramatically reduced myocardial uptake and blunted response to POCA. 18-[18F]Fluoro-6-thiaoctadecanoic acid (5) showed moderate myocardial uptake and no sensitivity of myocardial uptake to POCA. The results demonstrate relationships between structures of18F-labeled thia fatty acid and uptake and their utility as FAO probes in various tissues.