ArticleJournal of Alzheimer's disease : JAD2024
First Biodistribution Study of [68Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys.
Article in Journal of Alzheimer's disease : JAD, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- A phase 2A/B randomized trial of metabolic modulators intranasal insulin and empagliflozin for MCI and early AD.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Disease mechanisms and translational barriers guide nanocarrier design for nose to brain delivery in Alzheimer's disease.Discover nano · 2026Review
- Exercise Increases the Sensitivity of Cerebral Glucose Metabolism to Intranasal Insulin in Young, Healthy Adults.Journal of neurochemistry · 2026Article
- Intranasal Drug Delivery in Neuropharmacology: Advances in Brain-Targeted Therapies and Bioethical Challenges.Biomedicines · 2026Review
- Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial.Contemporary clinical trials communications · 2025Article
- First-in-human positron emission tomography study of intranasal insulin in aging and MCI.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Background: 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. Objective: To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system. Methods: 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. Results: 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. Conclusions: 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.
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