X-Ray Microbeam Radiation May Allow for More Effective Cancer Therapy

[Guest guest]

New X-ray Delivery Method Could Improve Radiation Therapy

June 5, 2006

UPTON, NY - Researchers at the U.S. Department of Energy's Brookhaven

National Laboratory and colleagues at Stony Brook University, the

IRCCS NEUROMED Medical Center in Italy, and town University say

improvements they have made to an experimental form of radiation

therapy that has been under investigation for many years could make

the technique more effective and eventually allow its use in

hospitals. Results on the improved method, which was tested in rats,

will be published online this week by the Proceedings of the National

Academy of Sciences.

The technique, microbeam radiation therapy (MRT), previously used a

high-intensity synchrotron x-ray source such as a superconducting

wiggler at Brookhaven's National Synchrotron Light Source (NSLS) to

produce parallel arrays of very thin (25 to 90 micrometers) planar x-

ray beams (picture the parallel panels of window blinds in the open

position) instead of the unsegmented (solid), broad beams used in

conventional radiation treatment. Previous studies conducted at

Brookhaven and at the European Synchrotron Radiation Facility (ESRF)

in Grenoble, France, demonstrated MRT's ability to control malignant

tumors in animals with high radiation doses while subjecting adjacent

normal tissue to little collateral damage.

But the technique has limitations. For one thing, only certain

synchrotrons can generate its very thin beams at adequate intensity,

and such facilities are available at only a few research centers

around the world.

" The new development seeks a way out of this situation, " explained

Brookhaven scientist Avraham Dilmanian, lead author of the new study.

In this paper, the scientists report results that demonstrate the

potential efficacy of significantly thicker microbeams, as well as a

way to " interlace " the beams within a well-defined " target " inside

the subject to increase their killing potential there, while

retaining the technique's hallmark feature of sparing healthy tissue

outside that target.

First, they exposed the spinal cords and brains of healthy rats to

thicker (0.27 to 0.68 millimeter) microbeams at high doses of

radiation and monitored the animals for signs of tissue damage. After

seven months, animals exposed to beams as thick as 0.68 millimeter

showed no or little damage to the nervous system.

" This demonstrates that the healthy-tissue-sparing nature of the

technique stays strong at a beam thickness that is within a range

that could be produced by specialized x-ray tubes of extremely high

voltage and current, " Dilmanian said. Such x-ray sources may become

available sometime in the future and may allow the implementation of

the method in hospitals.

Next, the scientists demonstrated the ability to " interlace " two

parallel arrays of the thicker microbeams at a 90-degree angle to

form a solid beam at a small target volume in the rats' brains, and

measured the effects of varying doses of radiation on the targeted

tissue volume and the surrounding tissue using magnetic resonance

imaging (MRI) scans. For interlacing, the gaps between the beams in

each array were chosen to be the same as the thickness of each beam,

so the beams from one array would fill the gaps in the other to

produce the equivalent of an unsegmented beam in the target volume

only.

" In this way we are effectively delivering an unsegmented broad beam

type of dose to just the target region — which could be a tumor, or a

non-tumerous target we want to ablate — while exposing the

surrounding tissue to segmented radiation from which it can recover, "

Dilmanian said.

The MRI scans showed that at a particular dose of radiation, the new

configuration could produce major damage to the target volume but

virtually no damage beyond the target range. " The dose of radiation

delivered to the target volume would have been enough to ablate a

malignant tumor, " Dilmanian said.

" These results show that thick microbeams generated by special x-ray

tubes in hospitals could eventually be used to destroy selective

targets while sparing healthy tissue, " Dilmanian said.

Said collaborator Eliot Rosen, a radiation oncologist at Lombardi

Comprehensive Cancer Center, town University, " This form of

microbeam radiation therapy could improve the treatment of many forms

of cancer now treated with radiation, because it can deliver a more

lethal dose to the tumor while minimizing damage to surrounding

healthy tissue. It may also extend the use of radiation to cases

where it is now used only judiciously, such as brain cancer in

patients under three years of age, because of the high sensitivity of

young brain tissue to radiation. "

And according to collaborators Anschel, a neurologist at Stony

Brook University and Brookhaven Lab, and Pantaleo Romanelli, a

neurosurgeon from NEUROMED Medical Center, the technique may also

have applications in treating a wide range of benign and malignant

brain tumors and other functional brain disorders such as epilepsy

and Parkinson's disease.

Background on MRT

MRT research was initiated by retired Brookhaven scientist

Slatkin, the late Per Spanne, also from Brookhaven, Dilmanian, and

others in the early 1990s at Brookhaven's NSLS. Since the mid 1990s,

the method has been under ongoing investigation also at ESRF.

It is not clear why high dose MRT is effective at killing tumor

tissue while sparing healthy tissue. The researchers hypothesize that

the normal tissue repairs itself, in part, as a result of the

survival between the microbeams of the microvasculature's angiogenic

cells. This effect seems to occur more successfully in the normal

tissue than in tumors, although other factors also seem to be

involved.

Neither the original nor the improved MRT technique has been tested

in humans.

The MRT research program at Brookhaven was funded in the past by

Brookhaven's Laboratory Directed Research and Development program,

the Children's Tumor Foundation, the Office of Biological and

Environmental Research within the U.S. Department of Energy's Office

of Science, and by the National Institutes of Health. The studies

were carried out at the NSLS, which is supported by the Office of

Basic Energy Sciences within DOE's Office of Science.

Upon publication, the PNAS paper will be available online at:

http://www.pnas.org/cgi/doi/10.1073/pnas.0603567103