Microbeam Radiation Therapy opens a several days vessel permeability window for small molecules in brain tumor vessels.

Potez, Marine; Rome, Claire; Lemasson, Benjamin; Heemeryck, Pierre; Laissue, Jean Albert; Stupar, Vasile; Mathieu, Hervé; Collomb, Nora; Barbier, Emmanuel; Djonov, Valentin; Bouchet, Audrey (2024). Microbeam Radiation Therapy opens a several days vessel permeability window for small molecules in brain tumor vessels. International journal of radiation oncology, biology, physics, 119(5), pp. 1506-1516. Elsevier 10.1016/j.ijrobp.2024.02.007

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PURPOSE

Synchrotron microbeam radiation therapy (MRT), based on an inhomogeneous geometric and microscopic irradiation pattern of the tissues with high dose and high dose rate X-rays, enhances the permeability of brain tumor vessels. This study attempts to determine time and size range of the permeability window induced by MRT in the blood brain (tumor) barrier.

METHODS AND MATERIALS

Rats-bearing 9L gliomas were exposed to MRT, either unidirectional (tumor dose 406 Gy), or bidirectional (crossfired) (2 × 203 Gy). We measured vessel permeability to molecules of 3 sizes (Gd-DOTA, Dotarem®, 0.56 kDa; gadolinium-labeled albumin, ∼74 kDa; gadolinium-labeled IgG, 160 kDa) by daily in vivo magnetic resonance imaging (MRI), from 1 day before to 10 days post-irradiation.

RESULTS

An equivalent tumor dose of bidirectional MRT delivered from two orthogonal directions increased tumor vessel permeability for the smallest molecule tested more effectively than unidirectional MRT. Bidirectional MRT also affected the permeability of normal contralateral vessels to a different extent than unidirectional MRT. Conversely, bidirectional MRT did not modify the permeability of normal or tumor vessels for both larger molecules (74 and 160 kDa).

CONCLUSIONS

High-dose bidirectional (cross-fired) MRT induced a significant increase in tumor vessel permeability for small molecules between the first and the seventh day after irradiation, while permeability of vessels in normal brain tissue remained stable. Such a permeability window could facilitate an efficient and safe delivery of intravenous small molecules (≤0.56 kDa) to tumoral tissues. A permeability window was not achieved by molecules larger than gado-grafted albumin (74 kDa). Vascular permeability for molecules between these two sizes has not been determined.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Potez, Marine Therese Charlette, Laissue, Jean, Djonov, Valentin Georgiev, Bouchet, Audrey Michele

Subjects:

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

ISSN:

1879-355X

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

21 Feb 2024 11:19

Last Modified:

24 Jul 2024 00:12

Publisher DOI:

10.1016/j.ijrobp.2024.02.007

PubMed ID:

38373658

Uncontrolled Keywords:

Synchrotron microbeam radiation therapy (MRT) blood brain (tumor) barrier brain tumor magnetic resonance imaging (MRI) small and larger contrast agents (0.56 to 160 kDa) vascular permeability window

BORIS DOI:

10.48350/193080

URI:

https://boris.unibe.ch/id/eprint/193080

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