{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:45:15Z","timestamp":1771490715587,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Local Government of the Regione Lazio"},{"name":"ENEA (Italian National Agency for New Technologies, Energy, and Sustainable Economic Development)"},{"name":"ISS (Italian National Institute of Health)"},{"name":"IFO-IRE (National Cancer Institute in Rome)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons. In addition, the brains of neonatal mice at postnatal day 5 (P5), representing a very small target, were irradiated with 6 Gy of protons with two different collimated Spread-Out Bragg Peaks (SOBPs). Apoptosis was visualized by immunohistochemistry for the apoptotic marker caspase-3-activated, and quantified by Western blot. Our findings proved that protons could be delivered to the upper part while sparing the deepest part of MB. In addition, a comparison of the effectiveness of protons and photons revealed a very similar increase in the expression of cleaved caspase-3. Finally, by using a very small target, the brain of P5-neonatal mice, we demonstrated that the proton irradiation field reached the desired depth in brain tissue. Using the TOP-IMPLART accelerator we established setup and procedures for proton irradiation, suitable for translational preclinical studies. This is the first example of in vivo experiments performed with a \u201cfull-linac\u201d proton-therapy accelerator.<\/jats:p>","DOI":"10.3390\/ijms24098281","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T04:55:50Z","timestamp":1683262550000},"page":"8281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Daniela","family":"Giovannini","sequence":"first","affiliation":[{"name":"ENEA SSPT-TECS-TEB, Casaccia Research Center, Division of Health Protection Technology (TECS), Agenzia Nazionale per le Nuove Tecnologie, l\u2019Energia e lo Sviluppo Economico Sostenibile (ENEA), Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0 (ISS), Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9967-5443","authenticated-orcid":false,"given":"Maria Denise","family":"Astorino","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2522-1718","authenticated-orcid":false,"given":"Emiliano","family":"Fratini","sequence":"additional","affiliation":[{"name":"ENEA SSPT-TECS-TEB, Casaccia Research Center, Division of Health Protection Technology (TECS), Agenzia Nazionale per le Nuove Tecnologie, l\u2019Energia e lo Sviluppo Economico Sostenibile (ENEA), Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evaristo","family":"Cisbani","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0 (ISS), Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Bazzano","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2964-6983","authenticated-orcid":false,"given":"Alessandro","family":"Ampollini","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Piccinini","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-MNF, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3832-7741","authenticated-orcid":false,"given":"Enrico","family":"Nichelatti","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-MNF, Casaccia Research Center, Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emiliano","family":"Trinca","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Nenzi","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0912-9287","authenticated-orcid":false,"given":"Mariateresa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"ENEA SSPT-TECS-TEB, Casaccia Research Center, Division of Health Protection Technology (TECS), Agenzia Nazionale per le Nuove Tecnologie, l\u2019Energia e lo Sviluppo Economico Sostenibile (ENEA), Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Picardi","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmela","family":"Marino","sequence":"additional","affiliation":[{"name":"ENEA SSPT-TECS-TEB, Casaccia Research Center, Division of Health Protection Technology (TECS), Agenzia Nazionale per le Nuove Tecnologie, l\u2019Energia e lo Sviluppo Economico Sostenibile (ENEA), Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Ronsivalle","sequence":"additional","affiliation":[{"name":"ENEA FSN-TECFIS-APAM, Frascati Research Center, Via Enrico Fermi 45, 00044 Frascati, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Pazzaglia","sequence":"additional","affiliation":[{"name":"ENEA SSPT-TECS-TEB, Casaccia Research Center, Division of Health Protection Technology (TECS), Agenzia Nazionale per le Nuove Tecnologie, l\u2019Energia e lo Sviluppo Economico Sostenibile (ENEA), Via Anguillarese 301, 00123 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1016\/j.ejca.2006.05.009","article-title":"Childhood central nervous system 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