Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1026, USA.
J Nucl Med. 2012 Mar;53(3):385-92. doi: 10.2967/jnumed.111.097162. Epub 2012 Feb 6.
Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high-affinity PET ligand, (11)C-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of (11)C-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile.
After intravenous injection of (11)C-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (V(T); a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise's bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose).
After (11)C-NOP-1A injection, the peak concentration of radioactivity in brain was high (∼5-7 standardized uptake values), occurred early (∼10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent V(T) identifiability (∼1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional V(T) values (mL·cm(-3)) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. V(T) was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of (11)C-NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 V(T) values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. (11)C-NOP-1A was significantly metabolized and excreted via the hepatobiliary route. Gallbladder had the highest radiation exposure (21 μSv/MBq), and the effective dose was 4.3 μSv/MBq.
(11)C-NOP-1A is a promising radioligand that reliably quantifies NOP receptors in human brain. The effective dose in humans is low and similar to that of other (11)C-labeled radioligands, allowing multiple scans in 1 subject.
我们之前开发了一种高亲和力的 PET 配体（11C-NOP-1A），该配体在猴脑中得到了有希望的结果。在这里，我们评估了（11C-NOP-1A）在人脑定量 NOP 受体的能力，并估计了其辐射安全性概况。
静脉注射（11C-NOP-1A）后，7 名健康受试者进行了 2 小时的脑 PET 扫描，并连续采集桡动脉血样以测量母体放射性配体浓度。分布容积（V（T）；受体密度的度量）通过隔室（1 和 2 组织）和非隔室（Logan 分析和 Ichise 的双线性分析[MA1]）方法确定。另一组 9 名健康受试者接受全身 PET 扫描以估计全身辐射暴露（有效剂量）。
（11C-NOP-1A）注射后，脑内放射性活性的峰值浓度较高（约 5-7 个标准化摄取值），出现较早（约 10 分钟），然后迅速清除。无约束的 2 组织隔室模型具有出色的 V（T）可识别性（约 1.1%SE），并且比 1 组织隔室模型更适合拟合数据。区域 V（T）值（mL·cm（-3））范围从颞叶的 10.1 到小脑的 5.6。在成像的最初 70 分钟内可以很好地识别 V（T），并且在剩余的 50 分钟内保持稳定，这表明脑放射性很可能是母体放射性配体，这一事实得到了支持，因为所有（11C-NOP-1A 的血浆放射性代谢产物都比母体放射性配体亲脂性差。基于体素的 MA1 V（T）值与 2 组织隔室模型的结果很好地相关，表明参数方法可用于比较人群。全身扫描显示脑和表达 NOP 受体的外周器官（如心脏、胰腺和脾脏）中的放射性。（11C-NOP-1A）明显通过肝胆途径代谢和排泄。胆囊的辐射暴露最高（21 μSv/MBq），有效剂量为 4.3 μSv/MBq。
（11C-NOP-1A）是一种很有前途的放射性配体，可可靠地定量人脑中的 NOP 受体。在人体中的有效剂量低且与其他（11C 标记的放射性配体相似，允许在 1 名受试者中进行多次扫描。
