Use of the NASA Space Radiation Laboratory at Brookhaven National Laboratory to Conduct Charged Particle Radiobiology Studies Relevant to Ion Therapy.

Although clinical studies with carbon ions have been conducted successfully in Japan and Europe, the limited radiobiological information about charged particles that are heavier than protons remains a significant impediment to exploiting the full potential of particle therapy. There is growing interest in the U.S. to build a cancer treatment facility that utilizes charged particles heavier than protons. Therefore, it is essential that additional radiobiological knowledge be obtained using state-of-the-art technologies and biological models and end points relevant to clinical outcome. Currently, most such ion radiotherapy-related research is being conducted outside the U.S. This article addresses the substantial contributions to that research that are possible at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), which is the only facility in the U.S. at this time where heavy-ion radiobiology research with the ion species and energies of interest for therapy can be done. Here, we briefly discuss the relevant facilities at NSRL and how selected charged particle biology research gaps could be addressed using those facilities.

Overview of the NASA space radiation laboratory.

The NASA Space Radiation Laboratory (NSRL) is a multidisciplinary center for space radiation research funded by NASA and located at the Brookhaven National Laboratory (BNL), Upton NY. Operational since 2003, the scope of NSRL is to provide ion beams in support of the NASA Humans in Space program in radiobiology, physics and engineering to measure the risk and ameliorate the effect of radiation in space. Recently, it has also been recognized as the only facility in the U.S. currently capable of contributing to heavy ion radiotherapy research. This work contains a general overview of NSRL structure, capabilities and operation.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory.

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

Biological characterization of low-energy ions with high-energy deposition on human cells.

During space travel, astronauts are exposed to cosmic radiation that is comprised of high-energy nuclear particles. Cancer patients are also exposed to high-energy nuclear particles when treated with proton and carbon beams. Nuclear interactions from high-energy particles traversing shielding materials and tissue produce low-energy (<10 MeV/n) secondary particles of high-LET that contribute significantly to overall radiation exposures. Track structure theories suggest that high charge and energy (HZE) particles and low-energy secondary ions of similar LET will have distinct biological effects for cellular and tissue damage endpoints. We investigated the biological effects of low-energy ions of high LET utilizing the Tandem Van de Graaff accelerator at the Brookhaven National Laboratory (BNL), and compared these to experiments with HZE particles, that mimic the space environment produced at NASA Space Radiation Laboratory (NSRL) at BNL. Immunostaining for DNA damage response proteins was carried out after irradiation with 5.6 MeV/n boron (LET 205 keV/µm), 5.3 MeV/n silicon (LET 1241 keV/µm), 600 MeV/n Fe (LET 180 keV/µm) and 77 MeV/n oxygen (LET 58 keV/µm) particles. Low-energy ions caused more persistent DNA damage response (DDR) protein foci in irradiated human fibroblasts and esophageal epithelial cells compared to HZE particles. More detailed studies comparing boron ions to Fe particles, showed that boron-ion radiation resulted in a stronger G2 delay compared to Fe-particle exposure, and boron ions also showed an early recruitment of Rad51 at double-strand break (DSB) sites, which suggests a preference of homologous recombination for DSB repair in low-energy albeit high-LET particles. Our experiments suggest that the very high-energy radiation deposition by low-energy ions, representative of galactic cosmic radiation and solar particle event secondary radiation, generates massive but localized DNA damage leading to delayed DSB repair, and distinct cellular responses from HZE particles. Thus, low-energy heavy ions provide a valuable probe for studies of homologous recombination repair in radiation responses.