{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:31:01Z","timestamp":1787067061369,"version":"build-2736575974"},"reference-count":39,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Intranasal insulin (INI) is being explored as a treatment for Alzheimer\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET\/CT scans.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We observed brain penetration of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]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\u200amSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185\u200aMBq.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The use of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-NOTA-insulin administration in humans.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-240484","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T10:06:51Z","timestamp":1724753211000},"page":"309-320","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["First Biodistribution Study of [\n                    <sup>68<\/sup>\n                    Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys"],"prefix":"10.1177","volume":"101","author":[{"given":"Kiran Kumar","family":"Solingapuram Sai","sequence":"first","affiliation":[{"name":"Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Erichsen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna K.","family":"Gollapelli","sequence":"additional","affiliation":[{"name":"Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Krizan","sequence":"additional","affiliation":[{"name":"Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mack","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Bansode","sequence":"additional","affiliation":[{"name":"Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew J.","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Register","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Cazzola","sequence":"additional","affiliation":[{"name":"Aptar Pharma, Le Vaudreuil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reenal","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Aptar Pharmaceuticals, Congers, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Suman","sequence":"additional","affiliation":[{"name":"Aptar Pharmaceuticals, Congers, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-023-01537-5"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1007\/BF01258634"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0287"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-9-S3-S5"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.11.002"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1840"},{"key":"ref008","unstructured":"Aptar. First Nasally-Administered Pharmaceutical Treatment for Dry Eye Disease Approved by US FDA with Aptar\u2019s Nasal Pump System Crytal Lake, IL, 2021."},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.2c00126"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600713475"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1177\/1091581817741840"},{"key":"ref012","unstructured":"CouncilNR. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, D.C.: The National Academies Press, 2011, p. 246."},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilt049"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1093\/geroni\/igaa057.389"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-015-0148-5"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.262034"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.3390\/ph14100990"},{"key":"ref018","first-page":"P1228","volume":"64","author":"Gollapelli KK","year":"2023","journal-title":"J Nucl Med"},{"key":"ref019","unstructured":"ICRP. Recommendations of the International Commission on Radiological Protection. Annals of the ICRP. Pergamon Press Oxford, 2008."},{"key":"ref020","unstructured":"ValentinJ. The 2007 recommendations of the international commission on radiological protection. 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