From MLZ to the clinic: Compact prototype enables microbeam radiotherapy for cancer in the smallest of spaces

A newly developed prototype at FRM II enables complex microbeam therapy for the first time, allowing it to be performed at a distance of only one and a half meters. Until now, this new form of radiation therapy, which enables better tumor control and fewer side effects than conventional methods, could only be performed using giant particle accelerators and was therefore not a realistic option for clinical use. The line-focus X-ray tube, the world’s first prototype of which was built at FRM II, could bring micro-radiation therapy into clinical application for the first time.

The prototype of the compact line-focus X-ray tube, measuring just one and a half meters, at FRM II. © Christian Petrich

The prototype of the compact line-focus X-ray tube, measuring just one and a half meters, at FRM II. © Christian Petrich

In conventional radiation therapy, the radiation is distributed evenly over the tumor, which can damage surrounding healthy cells and lead to side effects. Spatially fractionated radiotherapy divides the radiation field into high- and low-dose areas. These divisions are in the milli- and micrometer range and can thus irradiate the tumor cells with high precision. The advantage is obvious: healthy tissue regenerates well after irradiation, and the immune system is stimulated to learn how to fight the tumor more effectively.

The computer-controlled sample holder for tumor tissue of the line focus X-ray tube. © Elena Huber, FRM II / TUM

The computer-controlled sample holder for tumor tissue of the line focus X-ray tube. © Elena Huber, FRM II / TUM

What challenges the prototype overcomes

“The problem is that this type of radiation therapy requires a special radiation quality that, until now, could only be achieved in a few research facilities with special particle accelerators, called synchrotrons, which are several hundred meters in diameter,” explains Dr. Christian Petrich, co-developer of the prototype at FRM II. Without this precision, the radiation pattern becomes blurred in deeper tissue, and low dose rates result in prolonged irradiation times. Clinical applications have therefore been limited to the millimeter range and tumors close to the surface.
The newly developed prototype of a compact, only one and a half meter long line focus X-ray tube (LFXT) at FRM II overcomes these hurdles. By combining very high acceleration voltages and currents with an extremely precisely focused electron beam, it has been possible for the first time to generate microbeams in a tiny space without the need for huge synchrotron facilities. The LFXT thus opens up the potential for clinical use of radiation in the micrometer range and for deeper-seated tumors.

Fluorescence microscopy image of lung tumor cells, 30 minutes after microbeam irradiation. The effects of microbeam irradiation are clearly visible, with high-dose areas (green) indicating significant DNA damage. Conversely, areas with lower doses (blue) show less DNA damage. © Petrich et al. (2025)

Fluorescence microscopy image of lung tumor cells, 30 minutes after microbeam irradiation. The effects of microbeam irradiation are clearly visible, with high-dose areas (green) indicating significant DNA damage. Conversely, areas with lower doses (blue) show less DNA damage. © Petrich et al. (2025)

Precision confirmed

Tests confirm that the LFXT prototype generates radiation fields with clearly defined high-dose areas. Even in deeper tissue layers, the radiation pattern remains largely intact, which is a significant advantage over conventional devices.
This allows the high-dose, narrow beams to exert their effect on the immune system, mobilizing the body’s own defenses against the tumor.

Tumors under attack

In preclinical experiments, cancer cells were irradiated. Significant DNA damage occurred in the high-dose range, which deliberately destroyed the cells, while cells in the intermediate range were largely spared, allowing normal tissue to regenerate and the immune system to activate. This different response highlights the LFXT’s ability to deliver precise microbeam fields. Brain tumors in mice were also successfully treated with the new method. During several weeks of follow-up observation, no side effects or neurological impairments were observed, despite the high radiation dose.

Dr. Christian Petrich closes the cage surrounding the X-ray tube, protecting it from the high voltage required for the prototype. © Elena Huber, FRM II / TUM

Dr. Christian Petrich closes the cage surrounding the X-ray tube, protecting it from the high voltage required for the prototype. © Elena Huber, FRM II / TUM

Transfer to clinical practice