Purpose: Alpha particles, have been used in several cancer therapy modalities, including radionuclide therapy and brachytherapy using alpha emitters. Due to their high linear energy transfer (LET: 80-200 keV/μm), alpha particles cause clustered DNA lesions that are difficult to repair. Alpha particles have an extremely low range (approximately 5 cm in air and 50 μm in water for a 5 MeV particle), thereby making it extremely difficult to perform in vitro experiments. Because of this challenge, few alpha particle irradiators exist for the study of biological response, thereby limiting transformative translational research. To understand the biological consequences of alpha particles, we designed and constructed a cost-effective and high-throughput alpha particle irradiator.
Methods: Our irradiator was composed of an Am-241 source (50 mm x 50 mm, 1.35 μCi/mm2, NRD, LLC), collimator, and rotational motor to rotate the source to create a uniform fluence of particles. We also designed and constructed a specialized well with a mylar bottom (3 μm thickness) to hold cells and media. The bottom of the mylar is placed 1 cm from the Am-241 source.
Results: We successfully designed and constructed an alpha irradiator and a specialized water-tight well to hold cells and cell media. Our wells can withstand autoclaving procedures for sterilization, as well as extended exposure to incubator conditions. Additionally, plating efficiency optimization yielded successful cell adhesion to the mylar for multiple cancer cell lines. An advantage of our design is the ability to expose and conduct clonogenic assays within the same well. This feature removes uncertainty and labor associated with removing and resseding irradiated cells to another vessel and maximizes experimental efficiency.
Conclusion: With design and preliminary testing completed, we have created a reliable system that will enable planned research in alpha particle dosimetry and biological response of cancer cell lines to alpha particle radiation.
Funding Support, Disclosures, and Conflict of Interest: GOS and SFS have research funds from Alpha Tau Medical and Artios Pharma. Division of Radiation Oncology, MD Anderson Cancer Center