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Reliable in vivo discrimination between vascular and parenchymal A\u03b2 deposits (PEA) in AD is crucial for the assessment of CAA-related risks in anti-A\u03b2 immunotherapies. Current A\u03b2 PET tracers lack the ability to distinguish between vascular and parenchymal A\u03b2. The phenoxazine derivatives resorufin and ethyl-resorufin were previously shown to bind preferably to CAA over PEA. We therefore evaluated the fluorine-18-labeled resorufin derivative, [\n                      <jats:sup>18<\/jats:sup>\n                      F]fluoroethylresorufin ([\n                      <jats:sup>18<\/jats:sup>\n                      F]FER) as a potential PET tracer for selective in vivo detection of vascular A\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The binding specificity of [\n                      <jats:sup>3<\/jats:sup>\n                      H]FER was assessed using recombinant A\u03b2\n                      <jats:sub>1\u221240<\/jats:sub>\n                      and A\u03b2\n                      <jats:sub>1\u221242<\/jats:sub>\n                      fibrils as well as in vitro autoradiography on mouse brain tissue of APP23 (CAA+\/PEA+) and APPPS1 (CAA-\/PEA+) models, and compared to those of [\n                      <jats:sup>3<\/jats:sup>\n                      H]PIB. [\n                      <jats:sup>18<\/jats:sup>\n                      F]FER and its deuterated analog were synthesized for evaluation of brain pharmacokinetics, metabolism, and in vivo binding using PET imaging in wild-type, APPPS1, and APP23 mice. [\n                      <jats:sup>3<\/jats:sup>\n                      H]FER bound with higher affinity to A\u03b2\n                      <jats:sub>1\u221240<\/jats:sub>\n                      (K\n                      <jats:sub>d<\/jats:sub>\n                      = 9.4 nM) than to A\u03b2\n                      <jats:sub>1\u221242<\/jats:sub>\n                      (K\n                      <jats:sub>d<\/jats:sub>\n                      = 89.1 nM), consistent with its intended CAA selectivity. Autoradiography revealed preferential labeling of vascular amyloid in APP23 mice, with minimal binding in APPPS1 and wild-type tissue. In vivo, [\n                      <jats:sup>18<\/jats:sup>\n                      F]FER exhibited high brain uptake (peak SUV\u2009=\u20091.5) and rapid clearance, but metabolic degradation was fast, with ~\u200945% parent fraction remaining in the brain at 15\u00a0min. Deuteration did not improve stability but did improve washout kinetics. PET imaging with (d\n                      <jats:sub>4<\/jats:sub>\n                      )-[\n                      <jats:sup>18<\/jats:sup>\n                      F]FER demonstrated a cortical uptake pattern similar to [\n                      <jats:sup>11<\/jats:sup>\n                      C]PIB, indicating non-selective binding in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]FER showed promising in vitro affinity for vascular amyloid but lacked in vivo selectivity, likely due to rapid metabolism and high lipophilicity. These findings highlight the challenges of achieving in vivo CAA specificity and provide guidance for the optimization of future tracers targeting vascular A\u03b2 pathology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13550-026-01470-4","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:27:32Z","timestamp":1784168852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical evaluation of [18F]fluoroethylresorufin as PET tracer for cerebral amyloid angiopathy"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2216-2524","authenticated-orcid":false,"given":"Daniel","family":"Bleher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Poxleitner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2717-0723","authenticated-orcid":false,"given":"Ann-Kathrin","family":"Grotegerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1801-3080","authenticated-orcid":false,"given":"Oliver","family":"Hihn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6986-403X","authenticated-orcid":false,"given":"Laura","family":"Kuebler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-6738","authenticated-orcid":false,"given":"Gregory","family":"Bowden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7930-1919","authenticated-orcid":false,"given":"Martin","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian C.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4460-3113","authenticated-orcid":false,"given":"Bettina","family":"Weigelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-5524","authenticated-orcid":false,"given":"Bernd J.","family":"Pichler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-5361","authenticated-orcid":false,"given":"Andreas","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0231-7717","authenticated-orcid":false,"given":"Kristina","family":"Herfert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"1","key":"1470_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1046\/j.1440-1789.2000.00268.x","volume":"20","author":"M Yamada","year":"2000","unstructured":"Yamada M. 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