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The goal was to address limitations of the clinically used BPA\/[\u00b9\u2078F]FBPA pair, including poor water solubility, limited LAT1 specificity, and suboptimal diagnostic performance, thereby improving tumor-selective drug delivery and enabling accurate prediction of therapeutic biodistribution through structure-matched PET\/BNCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LAT1 dependency was tested in vitro using cancer cell lines with differential LAT1 expression. In vivo biodistribution of both therapeutic agents and their \u00b9\u2078F-labeled analogs were assessed in xenograft mouse models. Radiosynthesis of 5-[\u00b9\u2078F]F-\u03b1Me-3BPA was achieved via copper-catalyzed nucleophilic radiofluorination. PET\/CT imaging compared tumor visualization with [\u00b9\u2078F]FBPA. Co-injection studies (5-[\u00b9\u2078F]F-\u03b1Me-3BPA\/5F-\u03b1Me-3BPA and [\u00b9\u2078F]FBPA\/BPA) quantitatively evaluated concordance between \u00b9\u2078F radioactivity and boron concentrations across tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>5F-\u03b1Me-3BPA uptake in cancer cells was strictly LAT1-dependent. In LAT1-high T3M-4 xenografts, its tumor-to-muscle boron ratio (22) far exceeded BPA (3.4). 5-[\u00b9\u2078F]F-\u03b1Me-3BPA was synthesized successfully and achieved a tumor-to-muscle ratio of 29 versus 5.3 for [\u00b9\u2078F]FBPA. PET imaging showed clear, high-contrast visualization of T3M-4 tumors, with co-injection confirming strong concordance between PET probe and therapeutic agent biodistribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The 5-[\u00b9\u2078F]F-\u03b1Me-3BPA\/5F-\u03b1Me-3[\u00b9\u2070B]BPA theranostic pair demonstrates high LAT1 specificity, low normal tissue uptake, and strong pharmacokinetic alignment, enabling accurate prediction of therapeutic boron delivery for BNCT. Furthermore, 5-[\u00b9\u2078F]F-\u03b1Me-3BPA shows promise as a dedicated LAT1 imaging probe for advancing LAT1-targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07668-3","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:41:04Z","timestamp":1763458864000},"page":"2566-2577","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A LAT1-selective PET tracer, 5-[\u00b9\u2078F]F-\u03b1Me-3BPA, as a companion to its structurally matched \u00b9\u2070B analog in boron neutron capture therapy"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8082-8849","authenticated-orcid":false,"given":"Naoya","family":"Kondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuko","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasukazu","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7345-6004","authenticated-orcid":false,"given":"Takashi","family":"Temma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"7668_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.14338\/IJPT-22-00002.1","volume":"9","author":"WH Jin","year":"2022","unstructured":"Jin WH, Seldon C, Butkus M, Sauerwein W, Giap HB. 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The experimental protocols were approved by the Committee on Animal Experimentation of Osaka Medical and Pharmaceutical University. This article does not contain any studies with human participants performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Naoya Kondo, Fuko Hirano, Yasukazu Kanai, and Anna Miyazaki declare no competing interests. Takashi Temma has received research funding from Stella Pharma Corp. Kensuke Suzuki is an employee of Stella Pharma Corp.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}