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

Area of Science:

• Medical Physics
• Oncology
• Radiation Biology

Background:

• Proton therapy is increasingly used for pediatric medulloblastoma (MB).
• Preclinical research requires specialized setups for proton beam delivery in small animals.
• The TOP-IMPLART facility is a prototype linear accelerator for proton therapy.

Purpose of the Study:

• To design and characterize a proton beam delivery setup for in vivo radiobiology experiments.
• To assess the feasibility of the TOP-IMPLART accelerator for small animal proton therapy research.
• To evaluate proton beam targeting accuracy and biological effectiveness in preclinical models.

Main Methods:

• Irradiation of mice bearing Sonic-Hedgehog (Shh)-dependent MB with protons.
• Irradiation of neonatal mouse brains (postnatal day 5) with protons using collimated Spread-Out Bragg Peaks (SOBPs).
• Assessment of apoptosis via immunohistochemistry for cleaved caspase-3 and Western blot analysis.

Main Results:

• Proton beams were delivered to specific depths in tumor tissue, sparing deeper regions.
• Proton and photon irradiation showed similar induction of apoptosis (cleaved caspase-3 expression).
• Proton irradiation successfully targeted the desired depth in the small target of neonatal mouse brains.

Conclusions:

• The TOP-IMPLART accelerator setup and procedures are suitable for translational preclinical proton therapy studies.
• This work represents the first in vivo experiments using a full-linac proton therapy accelerator.
• The findings support the use of proton therapy for pediatric medulloblastoma research.