First-in-human evaluation of [(11)C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain.
First-in-human evaluation of [(11)C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain.
复制标题
DOI：
10.1007/s00259-020-04855-2
复制
发表时间：
2020-12
影响因子：
9.1
通讯作者：
Innis RB
中科院分区：
文献类型：
--
作者：
Kim MJ;Lee JH;Juarez Anaya F;Hong J;Miller W;Telu S;Singh P;Cortes MY;Henry K;Tye GL;Frankland MP;Montero Santamaria JA;Liow JS;Zoghbi SS;Fujita M;Pike VW;Innis RB
本研究评估了新开发的PET放射性配体[11 C]PS13是否可用于定量健康人脑中环氧合酶-1（考克斯-1）的组成性水平。在10名健康个体中获得了脑测试-重测扫描与同时动脉血样本。比较了单室模型和无约束双室模型以及Logan图形分析，并评估了总分布容积（VT）的重测信度和时间稳定性。在艾伦人脑图谱中提供的脑区域VT和考克斯-1转录水平之间进行相关性分析。在大脑中，[11 C]PS13在海马和枕叶皮质中显示出最高的摄取。与邻近的新皮质相比，中央周围皮质也显示出相对较高的摄取。两组织室模型在所有脑区中显示出最佳拟合，Logan图形分析的结果与两组织室模型的结果一致。VT值显示出极好的重测变异性（范围6.0-8.5%）和良好的可靠性（组内相关系数范围0.74-0.87）。VT值在所有脑区也显示出极好的时间稳定性，证实没有放射性代谢物积累，并且较短的扫描仍然能够可靠地测量VT。VT和考克斯-1转录水平之间观察到显著相关性（r = 0.82，P = 0.007），表明[11 C] PS 13结合反映了人脑中实际的考克斯-1密度。这些来自[11 C]PS13在脑中成像考克斯-1能力的首次人体评价的结果证明了将研究扩展到具有神经炎症的疾病人群是合理的。NCT 03324646，网址：https://clinicaltrials.gov/。2017年10月30日注册。已登记的逆行。
This study assessed whether the newly developed PET radioligand [11C]PS13, which has shown excellent in vivo selectivity in previous animal studies, could be used to quantify constitutive levels of cyclooxygenase-1 (COX-1) in healthy human brain. Brain test-retest scans with concurrent arterial blood samples were obtained in 10 healthy individuals. The one- and unconstrained two-tissue compartment models, as well as the Logan graphical analysis were compared, and test-retest reliability and time-stability of total distribution volume (VT) were assessed. Correlation analyses were conducted between brain regional VT and COX-1 transcript levels provided in the Allen Human Brain Atlas. In the brain, [11C]PS13 showed highest uptake in the hippocampus and occipital cortex. The pericentral cortex also showed relatively higher uptake compared with adjacent neocortices. The two-tissue compartment model showed the best fit in all the brain regions, and the results from the Logan graphical analysis were consistent with those from the two-tissue compartment model. VT values showed excellent test-retest variability (range 6.0–8.5%) and good reliability (intraclass correlation coefficient range 0.74–0.87). VT values also showed excellent time-stability in all brain regions, confirming that there was no radiometabolite accumulation and that shorter scans were still able to reliably measure VT. Significant correlation was observed between VT and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [11C]PS13 binding reflects actual COX-1 density in the human brain. These results from the first-in-human evaluation of the ability of [11C]PS13 to image COX-1 in the brain justifies extending the study to disease populations with neuroinflammation. NCT03324646 at https://clinicaltrials.gov/. Registered October 30, 2017. Retrospectively registered.
登录
查看更多内容
DOI：
10.1097/00004647-200007000-00011
发表时间：
2000-07-01
影响因子：
6.3
作者：
Parsey, RV;Slifstein, M;Laruelle, M
通讯作者：
Laruelle, M
影响因子：
15.9
作者：
KETY, SS;SCHMIDT, CF
通讯作者：
SCHMIDT, CF
影响因子：
9.3
作者：
Kim, Min-Jeong;Shrestha, Stal S.;Innis, Robert B.
通讯作者：
Innis, Robert B.
影响因子：
3.8
作者：
GANDELMAN, MS;BALDWIN, RM;INNIS, RB
通讯作者：
INNIS, RB
影响因子：
6.3
作者：
LOGAN, J;FOWLER, JS;CHRISTMAN, DR
通讯作者：
CHRISTMAN, DR