Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Solingapuram Sai, Kiran Kumara; 1 | Erichsen, Jennifer M.b; 1 | Gollapelli, Krishna K.a | Krizan, Ivana | Miller, Macka | Bansode, Avinasha | Jorgensen, Mathew J.c | Register, Thomasc | Cazzola, Charlesd | Gandhi, Reenale | Suman, Juliee | Craft, Suzanneb; *
Affiliations: [a] Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA | [b] Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA | [c] Department of Pathology, Division of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA | [d] Aptar Pharma, Le Vaudreuil, France | [e] Aptar Pharmaceuticals, Congers, NY, USA
Correspondence: [*] Correspondence to: Suzanne Craft, Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, One Medical Center Boulevard Winston-Salem, NC 27157, USA. Tel.: +1 336 713 8832; E-mail: suzcraft@wakehealth.edu.
Note: [1] These authors contributed equally to this work.
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.
Keywords: Alzheimer’s disease, insulin, intranasal administration, primates
DOI: 10.3233/JAD-240484
Journal: Journal of Alzheimer's Disease, vol. 101, no. 1, pp. 309-320, 2024
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl