Clinical Research Services Turku CRST, University of Turku, Itäinen Pitkäkatu 4 B, 20520, Turku, Finland,
Eur J Nucl Med Mol Imaging. 2015 Jan;42(1):120-7. doi: 10.1007/s00259-014-2899-z. Epub 2014 Sep 9.
α2C-Adrenoceptors share inhibitory presynaptic functions with the more abundant α2A-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α2-adrenoceptor subtypes.
PET imaging with the specific α2C-adrenoceptor antagonist tracer [(11)C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding.
The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [(11)C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method.
The results of this study support the use of [(11)C]ORM-13070 PET in the quantitative assessment of α2C-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios.
α2C-肾上腺素受体与更丰富的α2A-肾上腺素受体亚型共享抑制性突触前功能，但它们在大脑中也具有广泛的突触后调节功能。由于缺乏针对α2-肾上腺素受体亚型的合适 PET 示踪剂，因此对人类大脑去甲肾上腺素能系统的研究受到了阻碍。
在 6 名健康男性中进行了两次使用特异性α2C-肾上腺素受体拮抗剂示踪剂[11C]ORM-13070 的 PET 成像，以研究示踪剂结合的测试-重测可靠性。
在 5-30 分钟的时间间隔内，与小脑非特异性摄取相比，示踪剂摄取的结合/游离比在背侧纹状体中最为明显：在壳核中为 0.77，在尾状核中为 0.58。示踪剂结合/游离比的绝对测试-重测变异性范围从壳核的 4.3%到海马的 29%。尾状核和丘脑的变异性也<10%。内类相关系数（ICC）范围从海马的 0.50到丘脑的 0.89（尾状核、壳核、外侧额皮质和顶叶皮质也达到了 ICC>0.70）。PET 确定的[11C]ORM-13070 结合模式与先前从尸检放射自显影获得的受体密度结果非常吻合。与组织比法相比，使用房室模型拟合、简化参考组织模型和图形参考组织分析方法获得的 PET 数据分析结果是一致的。
本研究结果支持使用[11C]ORM-13070 PET 对体内人类大脑中的α2C-肾上腺素受体进行定量评估。借助参考组织比率，可以可靠地评估背侧纹状体中特异性示踪剂的结合。
