{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:20:24Z","timestamp":1792783224078,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","award":["22KK0123"],"award-info":[{"award-number":["22KK0123"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","award":["18H02771"],"award-info":[{"award-number":["18H02771"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","award":["16K15570"],"award-info":[{"award-number":["16K15570"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016690","name":"Sumitomo Electric Industries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016690","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Small Business Innovation Research (SBIR) program of Japan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Noninvasive imaging of protein aggregates in the brain is critical for the early diagnosis, disease monitoring, and evaluation of the effectiveness of novel therapies for Alzheimer\u2019s disease (AD). Near-infrared fluorescence (NIRF) imaging with specific probes is a promising technique for the\n                      <jats:italic>in vivo<\/jats:italic>\n                      detection of protein deposits without radiation exposure. Comprehensive screening of fluorescent compounds identified a novel compound, THK-565, for the\n                      <jats:italic>in vivo<\/jats:italic>\n                      imaging of amyloid-\u03b2 (A\u03b2) deposits in the mouse brain. This study assessed whether THK-565 could detect amyloid-\u03b2 deposits\n                      <jats:italic>in vivo<\/jats:italic>\n                      in the AD mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      The fluorescent properties of THK-565 were evaluated in the presence and absence of A\u03b2 fibrils. APP knock-in (APP-KI) mice were used as an animal model of AD.\n                      <jats:italic>In vivo<\/jats:italic>\n                      NIRF images were acquired after the intravenous administration of THK-565 and THK-265 in mice. The binding selectivity of THK-565 to A\u03b2 was evaluated using brain slices obtained from these mouse models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The fluorescence intensity of the THK-565 solution substantially increased by mixing with A\u03b2 fibrils. The maximum emission wavelength of the complex of THK-565 and A\u03b2 fibrils was 704\u00a0nm, which was within the optical window range. THK-565 selectively bound to amyloid deposits in brain sections of APP-KI mice After the intravenous administration of THK-565, the fluorescence signal in the head of APP-KI mice was significantly higher than that of wild-type mice and higher than that after administration of THK-265.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      analysis confirmed that the THK-565 signal corresponded to A\u03b2 immunostaining in the brain sections of these mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      A novel NIRF probe, THK-565, enabled the\n                      <jats:italic>in vivo<\/jats:italic>\n                      detection of A\u03b2 deposits in the brains of the AD mouse model, suggesting that NIRF imaging with THK-565 could non-invasively assess disease-specific pathology in AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-023-01843-4","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T15:23:17Z","timestamp":1692026597000},"page":"1115-1124","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Novel Near-Infrared Fluorescence Probe THK-565 Enables In Vivo Detection of Amyloid Deposits in Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.1007","volume":"25","author":[{"given":"Fumito","family":"Naganuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Maehori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozo","family":"Furumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukitsuka","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaho","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-7812","authenticated-orcid":false,"given":"Nobuyuki","family":"Okamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"1843_CR1","unstructured":"Zwan MD, Okamura N, Fodero-Tavoletti MT et al (2014) Voyage au bout de la nuit: A\u03b2\u00a0and tau imaging in dementias. Q J Nucl Med Mol Imaging 58:398\u2013412"},{"key":"1843_CR2","doi-asserted-by":"crossref","unstructured":"Okamura N, Harada R (2022) PET imaging of amyloid and tau in Alzheimer\u2019s disease. In Mori N (ed.) Aging Mechanisms II : Longevity, Metabolism, and Brain Aging. Singapore: Springer Nature Singapore, 307\u2013323","DOI":"10.1007\/978-981-16-7977-3_19"},{"key":"1843_CR3","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1517\/17530050903133790","volume":"3","author":"N Okamura","year":"2009","unstructured":"Okamura N, Fodero-Tavoletti MT, Kudo Y et al (2009) Advances in molecular imaging for the diagnosis of dementia. Expert Opin Med Diagn 3:705\u2013716","journal-title":"Expert Opin Med Diagn"},{"key":"1843_CR4","doi-asserted-by":"publisher","first-page":"8550","DOI":"10.1021\/acs.jmedchem.1c01619","volume":"65","author":"H Rai","year":"2022","unstructured":"Rai H, Gupta S, Kumar S et al (2022) Near-Infrared Fluorescent Probes as Imaging and Theranostic Modalities for Amyloid-Beta and Tau Aggregates in Alzheimer\u2019s Disease. J Med Chem 65:8550\u20138595","journal-title":"J Med Chem"},{"key":"1843_CR5","doi-asserted-by":"crossref","unstructured":"Hintersteiner M, Enz A, Frey P et al (2005) In vivo detection of amyloid-\u03b2 deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577\u2013583","DOI":"10.1038\/nbt1085"},{"key":"1843_CR6","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.1021\/acschemneuro.8b00306","volume":"9","author":"CP Chen","year":"2018","unstructured":"Chen CP, Liang ZY, Zhou B et al (2018) In Vivo Near-Infrared Two-Photon Imaging of Amyloid Plaques in Deep Brain of Alzheimer\u2019s Disease Mouse Model. ACS Chem Neurosci 9:3128\u20133136","journal-title":"ACS Chem Neurosci"},{"key":"1843_CR7","doi-asserted-by":"publisher","first-page":"5452","DOI":"10.1002\/anie.200500845","volume":"44","author":"EE Nesterov","year":"2005","unstructured":"Nesterov EE, Skoch J, Hyman BT, Klunk WE, Bacskai BJ, Swager TM (2005) In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markers. Angew Chem Int Ed Engl 44:5452\u20135456","journal-title":"Angew Chem Int Ed Engl"},{"key":"1843_CR8","doi-asserted-by":"publisher","first-page":"4701","DOI":"10.1039\/D2AN01327D","volume":"147","author":"Y Liu","year":"2022","unstructured":"Liu Y, Zhuang D, Wang J et al (2022) Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease. Analyst 147:4701\u20134723","journal-title":"Analyst"},{"key":"1843_CR9","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/alz.12673","volume":"19","author":"L Quan","year":"2023","unstructured":"Quan L, Moreno-Gonzalez I, Xie Z et al (2023) A near-infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer\u2019s disease. Alzheimers Dement 19:456\u2013466","journal-title":"Alzheimers Dement"},{"key":"1843_CR10","doi-asserted-by":"crossref","unstructured":"Wu J, Shao C, Ye X et al (2021) InVivo brain imaging of amyloid-\u03b2\u00a0aggregates in Alzheimer\u2019s disease with a near-infrared fluorescent probe. ACS Sens 6:863\u2013870","DOI":"10.1021\/acssensors.0c01914"},{"key":"1843_CR11","doi-asserted-by":"crossref","unstructured":"Zeng F, Yang J, Li X et al (2020) Versatile near-infrared fluorescent probe for in vivo detection of A\u03b2\u00a0oligomers. Bioorg Med Chem 28:115559","DOI":"10.1016\/j.bmc.2020.115559"},{"key":"1843_CR12","doi-asserted-by":"crossref","unstructured":"Chen Y, Yuan C, Xie T et al (2020) N, O-Benzamide difluoroboron complexes as near-infrared probes for the detection of \u03b2-amyloid and tau fibrils. Chem Commun (Camb) 56:7269\u20137272","DOI":"10.1039\/D0CC02820G"},{"key":"1843_CR13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3233\/JAD-2010-100270","volume":"23","author":"N Okamura","year":"2011","unstructured":"Okamura N, Mori M, Furumoto S et al (2011) In vivo Detection of Amyloid Plaques in the Mouse Brain using the Near-Infrared Fluorescence Probe THK-265. J Alzheimers Dis 23:37\u201348","journal-title":"J Alzheimers Dis"},{"key":"1843_CR14","doi-asserted-by":"crossref","unstructured":"Schmidt A, Pahnke J (2012) Efficient near-infrared in vivo imaging of amyoid-\u03b2\u00a0deposits in Alzheimer\u2019s disease mouse models. J Alzheimers Dis 30:651\u2013664","DOI":"10.3233\/JAD-2012-112168"},{"key":"1843_CR15","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s11060-011-0711-5","volume":"106","author":"A Ergin","year":"2012","unstructured":"Ergin A, Wang M, Zhang JY et al (2012) The feasibility of real-time in vivo optical detection of blood-brain barrier disruption with indocyanine green. J Neurooncol 106:551\u2013560","journal-title":"J Neurooncol"},{"key":"1843_CR16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck CH, Swanson CJ, Aisen P et al (2023) Lecanemab in Early Alzheimer\u2019s Disease. New Engl J Med 388:9\u201321","journal-title":"New Engl J Med"},{"key":"1843_CR17","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s40336-018-0290-y","volume":"6","author":"N Okamura","year":"2018","unstructured":"Okamura N, Harada R, Ishiki A, Kikuchi A, Nakamura T, Kudo Y (2018) The development and validation of tau PET tracers: current status and future directions. Clin Transl Imaging 6:305\u2013316","journal-title":"Clin Transl Imaging"},{"key":"1843_CR18","doi-asserted-by":"crossref","unstructured":"Gyasi YI, Pang YP, Li XR, et al. (2020) Biological applications of near infrared fluorescence dye probes in monitoring Alzheimer\u2019s disease. Eur J Med Chem 187:111982","DOI":"10.1016\/j.ejmech.2019.111982"},{"key":"1843_CR19","doi-asserted-by":"publisher","first-page":"9734","DOI":"10.1073\/pnas.1505420112","volume":"112","author":"XL Zhang","year":"2015","unstructured":"Zhang XL, Tian YL, Zhang C et al (2015) Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer\u2019s disease. P Natl Acad Sci USA 112:9734\u20139739","journal-title":"P Natl Acad Sci USA"},{"key":"1843_CR20","doi-asserted-by":"crossref","unstructured":"Ren WM, Zhang JJ, Peng C et al (2018) Fluorescent imaging of \u03b2-amyloid using BODIPY based near-infrared off-on fluorescent probe. Bioconjugate Chem 29:3459\u20133466","DOI":"10.1021\/acs.bioconjchem.8b00623"},{"key":"1843_CR21","doi-asserted-by":"crossref","unstructured":"Fu W, Yan CX, Guo ZQ et al (2019) Rational design of near-infrared aggregation-induced-emission- active probes: in situ mapping of amyloid-\u03b2 plaques with ultrasensitivity and high-fidelity. J Am Chem Soc 141:3171\u20133177","DOI":"10.1021\/jacs.8b12820"},{"key":"1843_CR22","doi-asserted-by":"crossref","unstructured":"Hou SS, Yang JY, Lee JH et al (2023) Near-infrared fluorescence lifetime imaging of amyloid-\u03b2 aggregates and tau fibrils through the intact skull of mice. Nat Biomed Eng 7:270\u2013280","DOI":"10.1038\/s41551-023-01003-7"},{"key":"1843_CR23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.apsb.2014.12.006","volume":"5","author":"HJ Tong","year":"2015","unstructured":"Tong HJ, Lou KY, Wang W (2015) Near-infrared fluorescent probes for imaging of amyloid plaques in Alzheimer\u2019s disease. Acta Pharm Sin B 5:25\u201333","journal-title":"Acta Pharm Sin B"},{"key":"1843_CR24","doi-asserted-by":"crossref","unstructured":"Ran C, Xu X, Raymond SB et al (2009) Design, synthesis, and testing of difluoroboron-derivatized curcumins as near-infrared probes for in vivo detection of amyloid-\u03b2 deposits. J Am Chem Soc 131:15257\u201315261","DOI":"10.1021\/ja9047043"},{"key":"1843_CR25","doi-asserted-by":"crossref","unstructured":"Watanabe H, Ono M, Matsumura K, Yoshimura M, Kimura H, Saji H (2013) Molecular imaging of \u03b2-amyloid plaques with near-infrared boron dipyrromethane (BODIPY)-based fluorescent probes. Mol Imaging 12:338\u2013347","DOI":"10.2310\/7290.2013.00049"},{"key":"1843_CR26","doi-asserted-by":"crossref","unstructured":"Ono M, Ishikawa M, Kimura H et al (2010) Development of dual functional SPECT\/fluorescent probes for imaging cerebral \u03b2-amyloid plaques. Bioorg Med Chem Lett 20:3885\u20133888","DOI":"10.1016\/j.bmcl.2010.05.027"},{"key":"1843_CR27","doi-asserted-by":"publisher","first-page":"13393","DOI":"10.1021\/jacs.7b05878","volume":"139","author":"P Verwilst","year":"2017","unstructured":"Verwilst P, Kim HR, Seo J et al (2017) Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe. J Am Chem Soc 139:13393\u201313403","journal-title":"J Am Chem Soc"}],"container-title":["Molecular Imaging and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11307-023-01843-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11307-023-01843-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11307-023-01843-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T13:10:27Z","timestamp":1702905027000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11307-023-01843-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,14]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["1843"],"URL":"https:\/\/doi.org\/10.1007\/s11307-023-01843-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2808428\/v1","asserted-by":"object"}]},"ISSN":["1536-1632","1860-2002"],"issn-type":[{"value":"1536-1632","type":"print"},{"value":"1860-2002","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,14]]},"assertion":[{"value":"12 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Drs Furumoto, Kudo, and Okamura have a patent pending for the technology described in this manuscript. No other potential conflicts of interest relevant to this article exist.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}