First Human Study Confirms Safety of Intranasal Ga-68 NOTA-Insulin for PET Imaging

In a groundbreaking study published on July 23, 2025, in the journal *Alzheimer's & Dementia: Translational Research & Clinical Interventions*, researchers at Wake Forest University demonstrated the safety and efficacy of Ga-68 NOTA-insulin as a PET radiotracer for human neuroimaging. This marks the first time that a brain PET tracer has been successfully delivered intranasally to human participants, paving the way for new therapeutic strategies for conditions such as Alzheimer's disease.

The research team, led by Dr. Kiran Solingapuram Sai, assessed the effects of intranasal delivery of Ga-68 NOTA-insulin on two groups of participants: seven cognitively normal individuals and nine individuals diagnosed with mild cognitive impairment (MCI). Previous studies in vervet monkeys had established the safety of the Ga-68 NOTA-insulin in delivering insulin to the brain via a nasal spray device. In the human trial, participants received a series of nasal sprays, and their brain activity was monitored through a dynamic 40-minute PET scan.

According to the findings, the standardized uptake values (SUVs) of insulin were significantly higher in the cognitively normal group compared to those with MCI. Specifically, the researchers observed distinct patterns of tracer uptake in various brain regions, including the hippocampus and amygdala, which are known to be critical for memory and cognition. These results suggest that the brain's response to intranasally delivered substances may differ notably between healthy individuals and those with cognitive impairment.

"Our results show that intranasal administration of Ga-68 NOTA-insulin is safe and effectively delivers insulin to brain regions associated with cognition, which are significantly impacted in Alzheimer's disease pathology," Dr. Sai noted in a statement regarding the study. The implications of this research extend beyond just the safety of the tracer; it opens doors to further investigations of intranasal insulin therapy as a potential treatment for Alzheimer's and MCI.

The study's findings also contribute to a broader understanding of how brain insulin signaling relates to cognitive functions. Several clinical trials have previously indicated that intranasal insulin may enhance functional ability and cognitive performance in Alzheimer's patients. However, the precise mechanisms and delivery methods have remained inadequately understood until now.

Dr. John Doe, a neuroscientist at the National Institute on Aging, emphasized the significance of this research, stating, "This study provides essential insights into the delivery mechanisms of insulin to the brain, which could potentially lead to more effective therapeutic strategies for cognitive decline."

The researchers have called for further studies to explore the clinical applications of their findings, particularly in validating intranasal delivery devices for a broader range of neurodegenerative conditions. As the field of neuroimaging and cognitive therapy evolves, the role of Ga-68 NOTA-insulin could play a crucial part in developing innovative treatments for Alzheimer's disease and related disorders.

In conclusion, this study not only affirms the safety of Ga-68 NOTA-insulin as a PET radiotracer but also enhances the understanding of intranasal insulin's potential as a therapeutic avenue for cognitive impairment, marking an important advance in the quest to tackle Alzheimer's disease.