Neurologic changes induced by whole-brain synchrotron microbeam irradiation: 10 months behavioral and veterinary follow-up.

Eling, L; Verry, C; Balosso, J; Flandin, I; Kefs, S; Bouchet, A; Adam, J F; Laissue, J A; Serduc, R (2024). Neurologic changes induced by whole-brain synchrotron microbeam irradiation: 10 months behavioral and veterinary follow-up. International journal of radiation oncology, biology, physics, 120(1), pp. 178-188. Elsevier 10.1016/j.ijrobp.2024.02.053

[img] Text
1-s2.0-S0360301624003729-main.pdf - Accepted Version
Restricted to registered users only until 8 March 2025.
Available under License Publisher holds Copyright.

Download (831kB)

PURPOSE

Novel 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 MATERIALS

Normal 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.

RESULTS

MBI 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.

CONCLUSIONS

While 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Laissue, Jean

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0360-3016

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

11 Mar 2024 15:45

Last Modified:

17 Aug 2024 00:12

Publisher DOI:

10.1016/j.ijrobp.2024.02.053

PubMed ID:

38462014

Uncontrolled Keywords:

Whole-brain irradiation behavioral and veterinary follow-up hospital broad beam normal rats radiotoxicity synchrotron microbeam X rays

BORIS DOI:

10.48350/194104

URI:

https://boris.unibe.ch/id/eprint/194104

Actions (login required)

Edit item Edit item
Provide Feedback