{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:33:02Z","timestamp":1777984382037,"version":"3.51.4"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR200046"],"award-info":[{"award-number":["RR200046"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI radiopharm. chem."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Boron neutron capture therapy relies on the selective accumulation of boron-containing compounds in tumor tissue, making accurate quantification of boron distribution essential for effective treatment planning. The amino acid analog boronophenylalanine is widely used as a boron delivery agent, yet direct assessment of its biodistribution remains challenging. A fluorine-18 labeled analog, 2-fluoro-boronophenylalanine, offers the potential to visualize and quantify uptake through positron emission tomography. However, reported radiosynthetic methods often suffer from low radiochemical yield, complex workflows, and limited compatibility with automated production platforms. The aim of this study was to design a stable precursor suitable for nucleophilic fluorination, develop a fully automated single-reactor radiosynthesis, and characterize the resulting tracer to support both preclinical use and future clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A rationally protected precursor incorporating tert-butyloxycarbonyl and pinacol ester groups was synthesized and isolated with high chemical and enantiomeric purity. Using this precursor, an automated single-pot radiosynthesis was implemented on a commercial synthesis module employing copper-mediated nucleophilic fluorination followed by acidic hydrolysis. Across eight production runs, the method yielded 2-fluoro-boronophenylalanine with non-decay-corrected radiochemical yields of 3\u20135% and a total synthesis time of approximately 60\u201370\u00a0min. Radiochemical purity consistently exceeded 98%, and the molar activity at the end of synthesis ranged from 85 to 120 GBq per micromole. The final formulation remained chemically and radiochemically stable for at least four hours at room temperature. Analytical and chiral chromatographic assessments confirmed product identity, purity, and retention of stereochemical configuration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study establishes a practical and fully automated radiosynthetic approach for producing 2-fluoro-boronophenylalanine using a single-reactor nucleophilic fluorination strategy. The method overcomes key limitations of electrophilic fluorination and multi-pot workflows, provides high radiochemical purity and suitable molar activity, and is compatible with commercially available synthesis equipment. These features support routine preclinical application and position the method for future current good manufacturing practice adaptation to enable clinical use in boron neutron capture therapy planning.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41181-026-00436-0","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:55:52Z","timestamp":1772708152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Automated radiosynthesis of 2-[18F]BPA for PET-based planning of boron neutron capture therapy (BNCT): rational precursor design, radiofluorination, and characterization of methodology"],"prefix":"10.1186","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0691-691X","authenticated-orcid":false,"given":"Vincenzo","family":"Paolillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong-Dat","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Ta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra K.","family":"Georgiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry Charles","family":"Manning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"436_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2022.108313","volume":"116","author":"TY Chang","year":"2023","unstructured":"Chang TY, et al. Comparison of the synthesis and biological properties of no-carrier-added and carrier-added 4-borono-2-[18F]fluorophenylalanine ([18F]FBPA). Nucl Med Biol. 2023;116:108313. https:\/\/doi.org\/10.1016\/j.nucmedbio.2022.108313.","journal-title":"Nucl Med Biol"},{"key":"436_CR2","doi-asserted-by":"publisher","unstructured":"He, et al. Nucleophilic radiosynthesis of boron neutron capture therapy-oriented PET probe [18F]FBPA using aryldiboron precursors. Chem Commun. 2021;57:8953. https:\/\/doi.org\/10.1039\/D1CC03369G.","DOI":"10.1039\/D1CC03369G"},{"issue":"4","key":"436_CR3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s12149-019-01347-8","volume":"33","author":"K Ishiwata","year":"2019","unstructured":"Ishiwata K. 4-borono-2-18F-fluoro-L-phenylalanine PET for boron neutron capture therapy-oriented diagnosis: overview of a quarter century of research. Ann Nucl Med. 2019;33(4):223\u201336. https:\/\/doi.org\/10.1007\/s12149-019-01347-8.","journal-title":"Ann Nucl Med"},{"key":"436_CR4","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.apradiso.2015.06.034","volume":"104","author":"S Mairinger","year":"2015","unstructured":"Mairinger S, Stanek J, Wanek T, Langer O, Kuntner C. Automated electrophilic radiosynthesis of [18F]FBPA using a modified nucleophilic GE TRACERlab FXFDG. Appl Radiat Isot. 2015;104:124\u20137. https:\/\/doi.org\/10.1016\/j.apradiso.2015.06.034.","journal-title":"Appl Radiat Isot"},{"key":"436_CR5","doi-asserted-by":"crossref","unstructured":"Mishima Y, Ichihashi M, Hatta S, Honda C, Yamamura K, Nakagawa T, Obara H, Shirakawa J, Hiratsuka J, Taniyama K et al. First human clinical trial of melanoma neutron capture. Diagnosis and therapy. Strahlenther Onkol. 1989 Feb-Mar;165(2\u20133):251-4.","DOI":"10.1007\/978-1-4684-5622-6_29"},{"issue":"2","key":"436_CR6","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s13139-021-00719-1","volume":"56","author":"S Naka","year":"2022","unstructured":"Naka S, Watanabe T, Kanai Y, Watabe T, Tatsumi M, Kato H, et al. Improved stability and practicality for synthesis of 4-borono-2-[18F]fluoro-l-phenylalanine by combination of [18O]O2 single-use and [18F]CH3COOF labeling agents. Nucl Med Mol Imaging. 2022;56(2):86\u201395. https:\/\/doi.org\/10.1007\/s13139-021-00719-1.","journal-title":"Nucl Med Mol Imaging"},{"issue":"12","key":"436_CR7","doi-asserted-by":"publisher","first-page":"ZE01","DOI":"10.7860\/JCDR\/2016\/19890.9024","volume":"10","author":"K Nedunchezhian","year":"2016","unstructured":"Nedunchezhian K, Aswath N, Thiruppathy M, Thirugnanamurthy S. Boron neutron capture therapy - a literature review. J Clin Diagn Res. 2016;10(12):ZE01-4. https:\/\/doi.org\/10.7860\/JCDR\/2016\/19890.9024.","journal-title":"J Clin Diagn Res"}],"container-title":["EJNMMI Radiopharmacy and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41181-026-00436-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41181-026-00436-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41181-026-00436-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:50:46Z","timestamp":1776077446000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41181-026-00436-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":7,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["436"],"URL":"https:\/\/doi.org\/10.1186\/s41181-026-00436-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8289343\/v1","asserted-by":"object"}]},"ISSN":["2365-421X"],"issn-type":[{"value":"2365-421X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"assertion":[{"value":"9 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}