Abstract：
JNJ-42491293 is a metabotropic glutamate 2 (mGlu2) positive allosteric modulator (PAM) that was radiolabelled with [11C]- to serve as a positron emission tomography (PET) ligand. Indeed, in vitro, the molecule displays high selectivity at mGlu2 receptors. However, PET experiments performed in rats, macaques and humans, have suggested that [11C]-JNJ-42491293 could interact with an unidentified, non-mGlu2 receptor binding site. The brain distribution of [11C]-JNJ-42491293 has not been determined in the brain of the common marmoset, a small non-human primate increasingly used in neuroscience research. Here, we investigated the distribution of [11C]-JNJ-42491293 in the marmoset brain. Three marmosets underwent brain magnetic resonance imaging (MRI) and 90-min dynamic PET scans with [11C]-JNJ-42491293 in combination with vehicle or the mGlu2 PAM AZD8529 (0.1, 1 and 10 mg/kg). In the scans in which [11C]-JNJ-42491293 was co-administered with vehicle, the brain areas with the highest standardised uptake values (SUVs) were the midbrain, cerebellum and thalamus, while the lowest SUVs were found in the pons. The addition of AZD8529 (0.1, 1 and 10 mg/kg) to [11C]-JNJ-42491293 did not modify the SUVs obtained with [11C]-JNJ-42491293 alone, and ex vivo blocking autoradiography with PAM AZD8529 (10, 100, 300 µM) on marmoset brain sections showed increased signals in the blocking conditions compared to vehicle, suggesting that no competition occurred between the 2 ligands. The results we obtained here do not suggest that [11C]-JNJ-42491293 interacts selectively, or even at all, with mGlu2 receptors in the marmoset, in agreement with findings previously reported in macaque and human.
摘要：
JNJ-42491293是一种代谢型谷氨酸2（mGlu2）正变构调节剂（PAM），用[11C]放射性标记-用作正电子发射断层扫描（PET）配体。的确,在体外，该分子对mGlu2受体显示出高选择性。然而,在大鼠中进行PET实验，猕猴和人类,建议[11C]-JNJ-42491293可以与身份不明的人互动，非mGlu2受体结合位点。[11C]-JNJ-42491293的脑分布尚未确定，一种越来越多地用于神经科学研究的小型非人类灵长类动物。这里,我们研究了[11C]-JNJ-42491293在the猴大脑中的分布。使用[11C]-JNJ-42491293与媒介物或mGlu2PAMAZD8529（0.1、1和10mg/kg）结合使用，对三只母马进行了脑磁共振成像（MRI）和90分钟动态PET扫描。在[11C]-JNJ-42491293与载体共同给药的扫描中，具有最高标准化摄取值（SUV）的大脑区域是中脑，小脑和丘脑,而最低的SUV是在桥墩中发现的。向[11C]-JNJ-42491293中添加AZD8529（0.1、1和10mg/kg）并没有改变单独使用[11C]-JNJ-42491293获得的SUV，与媒介物相比，用PAMAZD8529（10、100、300µM）在Marmoset脑切片上进行离体阻断放射自显影显示在阻断条件下信号增加，这表明2个配体之间没有竞争。我们在这里获得的结果并不表明[11C]-JNJ-42491293选择性地相互作用，甚至是，与mGlu2受体在the猴，与先前在猕猴和人类中报道的发现一致。
