{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:55:56Z","timestamp":1773770156053,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH, USA)","award":["AG 079189"],"award-info":[{"award-number":["AG 079189"]}]},{"name":"National Institutes of Health (NIH, USA)","award":["AG 029479"],"award-info":[{"award-number":["AG 029479"]}]},{"name":"National Institutes of Health (NIH, USA)","award":["AG 077700"],"award-info":[{"award-number":["AG 077700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The diagnostic value of imaging A\u03b2 plaques in Alzheimer\u2019s disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [18F]flotaza, which shows high binding to A\u03b2 plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [18F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [18F]flotaza in transgenic 5xFAD mice expressing A\u03b2 plaques. [18F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-A\u03b2 and analyzed using QuPath. In vitro and in vivo [18F]flotaza PET\/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-A\u03b2. High [18F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM\/WM &gt; 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WM\u2642\/WM\u2640 &gt; 5; p &lt; 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [18F]flotaza ratios (&gt;50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [18F]flotaza exhibited binding to A\u03b2 plaques in 5xFAD mice with SUVR~1.4. [18F]Flotaza is a new A\u03b2 plaque PET imaging agent that exhibited high binding to A\u03b2 plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [18F]flotaza to human PET studies may be worthwhile.<\/jats:p>","DOI":"10.3390\/ijms25147890","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T09:14:53Z","timestamp":1721380493000},"page":"7890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["[18F]Flotaza for A\u03b2 Plaque Diagnostic Imaging: Evaluation in Postmortem Human Alzheimer\u2019s Disease Brain Hippocampus and PET\/CT Imaging in 5xFAD Transgenic Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Yasmin K.","family":"Sandhu","sequence":"first","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4759-8022","authenticated-orcid":false,"given":"Harman S.","family":"Bath","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine","family":"Shergill","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Liang","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amina U.","family":"Syed","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6993-9131","authenticated-orcid":false,"given":"Allyson","family":"Ngo","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fariha","family":"Karim","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ 85351, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, AZ 85351, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-877X","authenticated-orcid":false,"given":"Jogeshwar","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrd3505","article-title":"The amyloid cascade hypothesis for Alzheimer\u2019s disease: An appraisal for the development of therapeutics","volume":"10","author":"Karran","year":"2011","journal-title":"Nat. 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