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In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model

TitoloIn Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2023
AutoriGiovannini, Daniela, De Angelis C., Astorino M.D., Fratini Emiliano, Cisbani E., Bazzano G., Ampollini A., Piccinini M., Nichelatti E., Trinca E., Nenzi P., Mancuso Mariateresa, Picardi L., Marino Carmela, Ronsivalle C., and Pazzaglia Simonetta
RivistaInternational Journal of Molecular Sciences
Parole chiaveanimal, Animals, caspase 3, Cerebellar Neoplasms, cerebellum tumor, medulloblastoma, Mice, mouse, proton, Protons, radiobiology

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 “full-linac” proton-therapy accelerator. © 2023 by the authors.


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Citation KeyGiovannini2023