Nanotube x-ray for cancer therapy: a compact microbeam radiation therapy system for brain tumor treatment

Abstract

Microbeam radiation therapy (MRT) is a promising preclinical modality for cancer treatment, with remarkable preferential tumoricidal effects, that is, tumor eradication without damaging normal tissue functions. Significant lifespan extension has been demonstrated in brain tumor-bearing small animals treated with MRT. So far, MRT experiments can only be performed in a few synchrotron facilities around the world. Limited access to MRT facilities prevents this enormously promising radiotherapy technology from reaching the broader biomedical research community and hinders its potential clinical translation. We recently demonstrated, for the first time, the feasibility of generating microbeam radiation in a laboratory environment using a carbon nanotube x-ray source array and performed initial small animal studies with various brain tumor models. This new nanotechnology-enabled microbeam delivery method, although still in its infancy, has shown promise for achieving comparable therapeutic effects to synchrotron MRT and has offered a potential pathway for clinical translation.

Keywords::

• brain tumor
• carbon nanotube
• glioblastoma multiforme
• image guidance
• microbeam radiation therapy
• temozolomide
• U87MG glioma
• x-ray
• γ-H2AX

Financial & competing interests disclosure

This work is supported by the National Cancer Institute (NCI)-funded Carolina Center for Cancer Nanotechnology Excellence (U54-CA151652) and the NCI Grand Opportunity grant (RC2-CA 148487). The CNT x-ray source array was manufactured by XinRay Systems. The U87 glioma cells were kindly provided by Dr. Ryan Miller’s lab at University of North Carolina at Chapel Hill Department of Pathology. The authors would also like to thank J Tepper at UNC Radiation Oncology for helpful discussions.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Brain tumors, especially glioblastoma multiforme, are among the most deadly cancers. So far, there has been no effective treatment to significantly extend the patients’ mean survival. Clinically used RT modalities often cause intolerable normal tissue toxicity to the circumjacent critical brain structures and the CNS.

• Microbeam radiation therapy (MRT) in small animal tumor models has shown strong tumor killing and normal tissue sparing effects.

• Until now, MRT research can only be carried out at a few remote synchrotron facilities and the therapeutic mechanism behind is still unclear. Widely accessible microbeam irradiators that can be readily installed in laboratories and medical centers are needed.

• Carbon nanotube (CNT) x-ray technology overcomes some of the limitations of conventional orthovoltage tubes and is the core of our technique for developing a compact MRT system for preclinical and, ultimately, clinical use.

• Utilizing the CNT source array, a prototype CNT-based microbeam irradiator has been developed and calibrated for preclinical studies.

• An MRI/x-ray combined image guidance protocol has been demonstrated to achieve a targeting accuracy of 450 µm in brain tumor mouse models.

• Preliminary studies in U87MG human glioma-bearing mice using the CNT MRT prototype have shown significant tumor growth suppression in MRT-treated groups compared to nontreated controls.

• Gated MRT is feasible using our proof-of-concept MRT prototype. It has been shown to be effective in reducing motion-induced microbeam blurring.

Notes