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Med. Biol."],"published-print":{"date-parts":[[2026,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    To verify the delivered dose in proton therapy\n                    <jats:italic>in vivo<\/jats:italic>\n                    using positron emission tomography (PET) with millimetric precision.\n                    <jats:italic>Approach.<\/jats:italic>\n                    Proton and ion therapy have gained significant importance in cancer radiotherapy due to their favorable dose distribution and tissue-sparing properties. In conventional gamma radiation therapy some methods of\n                    <jats:italic>in vivo<\/jats:italic>\n                    dose verification are possible with current medical devices. In proton and ion therapy, dose verification is limited, with PET being mainly used for particle range assessments rather than full dose mapping. Prompt gamma techniques are well suited for range verification but are not suitable for full three-dimensional (3D), voxel-wise dose mapping. This study presents initial results for\n                    <jats:italic>in vivo<\/jats:italic>\n                    dose verification using F-18 PET imaging during proton therapy. Although the activity concentration of F-18 generated by typical clinical doses (several Gy) is low, PET imaging performed approximately one-hour post-irradiation yields sufficient image quality to derive dose\u2013volume histograms (DVHs), enabling spatial dose verification. We simulated proton treatment in a brain phantom using the Gate and RayStation platforms to assess the production of several positron emitting isotopes. We focused on the production of fluorine-18 (F-18), given its low positron energy and low energy threshold for production, which enables accurate replication of the dose distribution. To evaluate the detectability of the anticipated low activity concentrations (on the order of a fraction of a Bq ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) following a 3 Gy proton irradiation, we tested three PET systems: two preclinical scanners based on LYSO detectors and one clinical scanner based on BGO crystals. Finally, we analyzed the DVHs for the simulated and measured dose and activity distributions and compared them with the planned distribution.\n                    <jats:italic>Main Results.<\/jats:italic>\n                    F-18 PET imaging in proton therapy correlates with the delivered dose to within 5% and matches the planned dose fall-off edge within 1 mm, enabling accurate and precise\n                    <jats:italic>in vivo<\/jats:italic>\n                    dose verification.\n                    <jats:italic>Significance.<\/jats:italic>\n                    F-18 enables more accurate proton-therapy dose verification than other positron emitters studied (C-11, N-13, and O-15), showing the closest spatial correspondence to the planned dose and activity levels post-therapy that remain detectable on modern BGO-based PET systems.\n                  <\/jats:p>","DOI":"10.1088\/1361-6560\/ae5d7f","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T22:52:07Z","timestamp":1775775127000},"page":"105009","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Precise dose verification in proton therapy via F-18 activation measured with positron emission tomography imaging"],"prefix":"10.1088","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6030-7416","authenticated-orcid":true,"given":"Marcin","family":"Balcerzyk","sequence":"first","affiliation":[{"name":"Bioaraba Health Research Institute, New Technologies and Information Systems in Health Research Group"},{"name":"IKERBASQUE, Basque Foundation of Science"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1150-383X","authenticated-orcid":true,"given":"Marta","family":"Freire","sequence":"additional","affiliation":[{"name":"I3M, CSIC-Universitat Polit\u00e8cnica de Val\u00e8ncia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3135-4501","authenticated-orcid":false,"given":"Rub\u00e9n Fernandez","family":"de la Rosa","sequence":"additional","affiliation":[{"name":"Instituto Pluridisciplinar, Universidad Complutense de Madrid"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-0513","authenticated-orcid":false,"given":"Miguel Angel","family":"Pozo","sequence":"additional","affiliation":[{"name":"Instituto Pluridisciplinar, Universidad Complutense de Madrid"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9359-4730","authenticated-orcid":false,"given":"Rhodri Lyn","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Alberta"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5129-537X","authenticated-orcid":true,"given":"Gaspar","family":"Sanchez-Merino","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, New Technologies and Information Systems in Health Research Group"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-5626","authenticated-orcid":true,"given":"Antonio J","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"I3M, CSIC-Universitat Polit\u00e8cnica de Val\u00e8ncia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"pmbae5d7fbib1","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/ad7d5c","type":"journal-article","article-title":"RayStation\/GATE Monte Carlo simulation framework for verification of proton therapy based on the N-12 imaging","volume":"69","author":"Ahmadi Ganjeh","year":"2024","journal-title":"Phys. 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Published on behalf of Institute of Physics and Engineering in Medicine by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2025-09-09","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-04-09","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-05-20","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}