Gallium-68 (Ga-68) NOTA-insulin is a safe and effective PET radiotracer for assessing intranasal delivery of insulin to the brain in humans, researchers have reported.
With intranasal insulin being explored to treat Alzheimer’s disease and other conditions, researchers now have a way to visualize patient responses to the therapy, noted first author Kiran Solingapuram Sai, PhD, of Wake Forest University in Winston-Salem, NC, and colleagues.
“Our results show that intranasal administration of Ga-68 NOTA-insulin is safe and delivers insulin to multiple brain regions that support cognition and are affected by Alzheimer’s disease pathology,” the group wrote. The study was published July 23 in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
Brain insulin signaling contributes to memory function, and several clinical trials have shown that intranasal insulin (INI) improves functional ability and cognition in Alzheimer’s disease patients, the authors explained. Yet for INI to be clinically considered a viable therapeutic strategy, more must be understood about its delivery to the brain, they noted.
To that end, the group developed the PET tracer Ga-68 NOTA-insulin and previously established its safety and effectiveness in healthy adult vervet monkeys after administering it with a nasal spray device. In this study, they assessed the technique for the first time in humans.
The researchers enrolled seven cognitively normal (CN) participants and nine participants with mild cognitive impairment (MCI). Participants had previously undergone brain PET scans to establish baseline measurements.
For the experiment, the participants sat upright on the PET scanner and received a spray of Ga-68 NOTA-insulin into each nostril. This was repeated twice more (six sprays total), with 30 seconds between each set. Within five minutes of the final spray, participants then underwent a dynamic 40-minute brain PET scan (Discovery MI DR, GE HealthCare).
According to the analysis, mean insulin standardized uptake values (SUVs) were higher for CN participants than for participants with MCI in the hippocampus, parahippocampus, amygdala, olfactory cortex, and thalamus.
In addition, the researchers generated time activity curves (TACs) for each brain region and performed a separate analysis for each group. The TACs indicated distinct tracer uptake patterns between the subjects. In the CN group, peak uptake occurred at approximately 750 seconds in all regions, except for the cingulum, which peaked at 150 seconds. In contrast, the MCI group peaked at approximately 150 seconds across all regions, suggesting altered tracer uptake.
Finally, a faster radiotracer clearance rate was observed in MCI relative to the CN group.
“These observations suggest that brain uptake and distribution of intranasally delivered substances may differ for adults with [mild cognitive impairment],” the group wrote.
Ultimately, the study confirms the safety and efficacy of Ga-68 NOTA-insulin as a PET radiotracer that can be used for human neuroimaging, and provides a means of validating intranasal delivery devices, the group wrote.
“Our data provide critical information to guide future studies of INI as a treatment for [mild cognitive impairment] and [Alzheimer’s disease],” the researchers concluded.
The full study is available here.