■鼻内胰岛素(INI)正在探索作为阿尔茨海默病(AD)的治疗方法。改善记忆,功能能力,和脑脊液(CSF)AD生物标志物谱在INI给药后观察到。然而,鼻内给药方式可能显著影响结局.
■显示使用Aptar药筒泵系统(CPS)鼻内输送系统将胰岛素可靠地输送到大脑。
■为了可视化INI生物分布,我们开发了一种新型PET放射性示踪剂,镓68-放射性标记(NOTA缀合)胰岛素,[68Ga]Ga-NOTA-胰岛素。我们使用AptarCPS向麻醉的健康成年长尾猴施用[68Ga]Ga-NOTA-胰岛素,并在PET/CT扫描后测量大脑区域活动和全身剂量测定。
我们观察到在用AptarCPS鼻内施用后[68Ga]Ga-NOTA-胰岛素的脑渗透。放射性摄取见于多个区域,包括杏仁核,壳核,下丘脑,海马体,和脉络丛.在第二组Vervets中还建立了安全性和全身剂量学。安全性得到证实:生命体征保持稳定,血糖水平没有变化,并且没有器官暴露于超过2.5mSv的放射性。从vervet器官分布推断,可以估计人类[68Ga]Ga-NOTA-胰岛素吸收剂量,并且可以安全施用于人的[68Ga]Ga-NOTA-胰岛素的最大剂量被确定为185MBq。
■使用[68Ga]Ga-NOTA-胰岛素作为PET放射性示踪剂对于观察长尾猴的脑摄取是安全且有效的。Further,AptarCPS成功地将[68Ga]Ga-NOTA-胰岛素靶向大脑。该数据对于指导人体鼻内[68Ga]Ga-NOTA-胰岛素给药的未来研究至关重要。
UNASSIGNED: Intranasal insulin (INI) is being explored as a treatment for Alzheimer\'s disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes.
UNASSIGNED: To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system.
UNASSIGNED: To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [68Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [68Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET/CT scans.
UNASSIGNED: We observed brain penetration of [68Ga]Ga-NOTA-insulin following intranasal administration with the Aptar CPS. Radioactive uptake was seen in multiple regions, including the amygdala, putamen, hypothalamus, hippocampus, and choroid plexus. A safety profile and whole-body dosimetry were also established in a second cohort of vervets. Safety was confirmed: vitals remained stable, blood glucose levels were unchanged, and no organ was exposed to more than 2.5 mSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [68Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [68Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185 MBq.
UNASSIGNED: The use of [68Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [68Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [68Ga]Ga-NOTA-insulin administration in humans.