Bergström M, Lu L, Marquez M, Fasth K J, Bjurling P, Watanabe Y, Eriksson B, Långström B
Uppsala University PET Centre, Sweden.
Nucl Med Biol. 1997 Jan;24(1):15-9. doi: 10.1016/s0969-8051(96)00149-7.
The present study was undertaken to investigate if pretreatment with pharmacological agents could change the organ uptake of 11C-labelled L-DOPA, and especially if the urinary excretion could be decreased. L-[beta-11C]DOPA was injected IV into unanesthetized Sprague-Dawley rats. After 20 min the rats were decapitated and organs taken out for radioactivity measurements. The uptake in the organs was investigated in animals only given the tracer, and in animals pretreated with drugs such as decarboxylase inhibitors carbidopa and benserazide as well as the monoamine oxidase inhibitors deprenyl, clorgyline, and the COMT inhibitor OR-486. A marked decrease in the urinary radioactivity was observed after carbidopa and benserazide administration. HPLC analysis revealed that under native conditions the major part of urinary radioactivity existed as dopamine, which was eliminated by the decarboxylase inhibitors. After pretreatment with the COMT inhibitor OR-486, the radioactivity uptake in the pancreas increased fourfold as compared to non-treated animals. HPLC analysis showed that this correlated with a marked increase in radiolabelled DOPAC. In the other organs and with the other drugs, only small effects were observed. With L-[beta-11C]fluoroDOPA as a tracer, similar results were observed although the increase in the pancreas by OR-486 had a lower magnitude. These studies suggest that it might be possible to improve the diagnostic ratio of L-[beta-11C]DOPA or L-[18F]fluoroDOPA in whole-body PET studies by pretreating the patient with decarboxylase inhibitor for reducing the urinary excretion and potentially increase the target organ uptake by COMT inhibition.
本研究旨在调查用药物制剂进行预处理是否会改变¹¹C标记的左旋多巴在器官中的摄取，特别是是否可以减少尿排泄。将L-[β-¹¹C]多巴静脉注射到未麻醉的Sprague-Dawley大鼠体内。20分钟后，将大鼠断头并取出器官进行放射性测量。在仅给予示踪剂的动物以及用脱羧酶抑制剂卡比多巴和苄丝肼、单胺氧化酶抑制剂司来吉兰、氯吉兰以及儿茶酚-O-甲基转移酶（COMT）抑制剂OR-486预处理的动物中研究器官摄取情况。给予卡比多巴和苄丝肼后，观察到尿放射性明显降低。高效液相色谱（HPLC）分析显示，在天然条件下，尿放射性的主要部分以多巴胺形式存在，脱羧酶抑制剂可将其消除。用COMT抑制剂OR-486预处理后，与未处理的动物相比，胰腺中的放射性摄取增加了四倍。HPLC分析表明，这与放射性标记的3,4-二羟基苯乙酸（DOPAC）的显著增加相关。在其他器官以及使用其他药物时，仅观察到微小影响。以L-[β-¹¹C]氟多巴作为示踪剂时，观察到了类似结果，尽管OR-486对胰腺的增加幅度较小。这些研究表明，通过用脱羧酶抑制剂预处理患者以减少尿排泄，并通过抑制COMT潜在地增加靶器官摄取，有可能提高全身正电子发射断层扫描（PET）研究中L-[β-¹¹C]多巴或L-[¹⁸F]氟多巴的诊断率。
