Live monitoring at cell level during proton therapy

Irradiation with protons instead of X-rays is an important addition in the treatment of tumors. In order to optimize proton therapy, further research is needed into its precise radiobiological effects. To this end, researchers at Erasmus MC and TU Delft have developed a unique set-up to observe what happens in cells during proton therapy. The collaboration between different universities and disciplines is a fine example of convergence.

Radiation with protons, also known as proton therapy, can very specifically destroy the cell nuclei of tumors containing the DNA, while the surrounding tissues are barely damaged. However, proton therapy is more expensive than radiation with photons, so more research is needed into how it can be used most effectively. Tim Heemskerk, PhD student in molecular genetics in the group of Dr Jeroen Essers, Erasmus MC, is investigating how cells respond to the damage caused by the proton beam, depending on the dose and intensity. “We want to follow cells before, during and after proton irradiation. Using fluorescence techniques, we color proteins that play a role in DNA repair. During irradiation, this allows us to follow exactly how those processes occur.” The ultimate goal is to fine-tune proton therapy as best as possible, so that the dose is delivered to exactly the right place with as few side effects as possible.

At the Holland Proton Therapy Center (HollandPTC), an independent outpatient center founded by Erasmus MC, LUMC and TU Delft, there is a particle accelerator that generates a proton beam. Radiation physicist Dr. Marta Rovituso of HollandPTC supports researchers like Heemskerk with the physics aspects of their research. “I take care of absolute dosimetry: delivering exactly the desired radiation dose at the exact location of the cells. Tim then looks at the biological effects of the radiation. What’s unique about this project is that a microscope was placed in the beam line to watch the effects in real time.”

Perfectly in place
Within Erasmus MC, the Optical Imaging Centre (OIC) is the core facility for everything related to microscopy. The OIC faced a special task due to the request from Heemskerk, Essers and Rovituso. “The proton beam comes out of the wall horizontally,” says OIC specialist Dr. Johan Slotman. “So we had to tilt the microscope 90 degrees. That sounds simple, but it’s not trivial.” The challenge for Slotman and his colleague Dr. Gert-Jan Kremers was to position the cell culture vertically. “The glass plate with the cell culture has to be constantly heated at 37 degrees, so that the cells stay alive. Between the glass and the lens of the microscope there is also a thin layer of oil. All of that has to stay perfectly in place.” Together with Ernst van der Wal, team leader at TU Delft’s Electrical and Mechanical Support Office (DEMO), the necessary components were developed.

The group presented the project at the Open Mind Conference 2021 and received a grant of 20 thousand euros. Heemskerk: “That was enough to get to a proof of principle. The setup works and we will start experimenting soon.” Moreover, an application is being prepared for a more advanced microscope. But the project also opens other doors, says Rovituso: “This setup can be used for a wide range of biological and physical research.” Slotman: “Thanks to the Open Mind, the collaboration within the convergence has gone from loose to very solid. And that is exactly the intention.”

Tim Heemskerk
Erasmus MC