Neurologic Changes Induced by Whole-Brain Synchrotron Microbeam Irradiation: 10-Month Behavioral and Veterinary Follow-Up

Abstract

PurposeNovel radiotherapy approaches have increased the therapeutic efficacy for malignant brain tumors over the last decades but the balance between therapeutic gain and radiotoxicity remains a medical hardship. Synchrotron Microbeam Radiation Therapy (MRT), an innovative technique, deposes extremely high (peak) doses in micron-wide, parallel microbeam paths, while the diffusing inter-beam (valley) doses lie in the range of conventional radiotherapy doses. In this study, we evaluated normal tissue toxicity of whole-brain microbeam irradiation (MBI) versus that of a conventional, hospital broad beam (hBB). Methods and MaterialsNormal Fischer rats (n=6-7/group) were irradiated with one of the two modalities, exposing the entire brain to 0, 5/200, 10/400, 13/520, 17/680 or 25/1000 Gy MBI valley/peak dose, or to 7, 10, 13, 17 or 25 Gy hBB dose. Two additional groups of rats received 10 Gy MBI valley dose coupled with 7 or 15 Gy BB dose (groups MBI17* and MBI25*). Behavioral parameters were evaluated for 10 months post irradiation, combined with veterinary observations. ResultsMBI peak doses of ≥680 Gy caused acute toxicity and death. Animals exposed to hBB or MBI dose-dependently gained less weight than controls; rats in the hBB25 and MBI25* groups deceased within 6 months post irradiation. Increasing doses of MBI caused hyperactivity but no other detectable behavioral alteration in our tests. Importantly, no health concerns were seen up to 17 Gy MBI valley dose. ConclusionsWhile acute toxicity of microbeam exposures depends on very high peak doses, late toxicity mainly relates to delivery of high MBI valley doses. MBI seems to elicit low impact on normal rat behavior but further tests are warranted to fully explore this hypothesis. However, high peak and valley doses are well tolerated from a veterinary point of view. This normal tissue tolerance to whole-brain, high-dose MBI reveals a promising avenue for MRT, i.e., therapeutic applications of microbeams which are poised for translation to a clinical environment.