ABSTRACT
BACKGROUND AND PURPOSE: Medulloblastoma (MB) is a common primary brain cancer in children. Proton therapy in pediatric MB is intensively studied and widely adopted. Compared to photon, proton radiations offer potential for reduced toxicity due to the characteristic Bragg Peak at the end of their path in tissue. The aim of this study was to compare the effects of irradiation with the same dose of protons or photons in Patched1 heterozygous knockout mice, a murine model predisposed to cancer and non-cancer radiogenic pathologies, including MB and lens opacity. MATERIALS AND METHODS: TOP-IMPLART is a pulsed linear proton accelerator for proton therapy applications. We compared the long-term health effects of 3 Gy of protons or photons in neonatal mice exposed at postnatal day 2, during a peculiarly susceptible developmental phase of the cerebellum, lens, and hippocampus, to genotoxic stress. RESULTS: Experimental testing of the 5 mm Spread-Out Bragg Peak (SOBP) proton beam, through evaluation of apoptotic response, confirmed that both cerebellum and hippocampus were within the SOBP irradiation field. While no differences in MB induction were observed after irradiation with protons or photons, lens opacity examination confirmed sparing of the lens after proton exposure. Marked differences in expression of neurogenesis-related genes and in neuroinflammation, but not in hippocampal neurogenesis, were observed after irradiation of wild-type mice with both radiation types. CONCLUSION: In-vivo experiments with radiosensitive mouse models improve our mechanistic understanding of the dependence of brain damage on radiation quality, thus having important implications in translational research.
Subject(s)
Animals, Newborn , Apoptosis , Hippocampus , Photons , Proton Therapy , Animals , Mice , Apoptosis/radiation effects , Proton Therapy/adverse effects , Hippocampus/radiation effects , Medulloblastoma/radiotherapy , Medulloblastoma/pathology , Carcinogenesis/radiation effects , Mice, Knockout , Cerebellar Neoplasms/radiotherapy , Cerebellar Neoplasms/pathology , Brain/radiation effects , Patched-1 Receptor/genetics , Disease Models, Animal , Protons/adverse effectsABSTRACT
The TOP-IMPLART, a new proton therapy facility, is under development in Frascati ENEA Laboratories, near Rome. The project is centered on a medium-energy proton accelerator designed as a sequence of modular linear accelerators (the final energy will be 230 MeV). Being not a commercial product, measurements and simulation are fundamental to characterize the system and the radiation field, even during its construction. In this work some preliminary evaluations of the neutron contamination have been tried. The simulations were validated through some measurements obtaining a satisfactory agreement. A more detailed calculations and measurements campaign is scheduled for the next future.
