Abstract
The use of alpha particles irradiation in clinical practice has gained interest in the past years, for example with the advance of radionuclide therapy. The lack of affordable and easily accessible irradiation systems to study the cell biological impact of alpha particles hampers broad investigation. Here we present a novel alpha particle irradiation set-up for uniform irradiation of cell cultures. By combining a small alpha emitting source and a computer-directed movement stage, we established a new alpha particle irradiation method allowing more advanced biological assays, including large-field local alpha particle irradiation and cell survival assays. In addition, this protocol uses cell culture on glass cover-slips which allows more advanced microscopy, such as super-resolution imaging, for in-depth analysis of the DNA damage caused by alpha particles. This novel irradiation set-up provides the possibility to perform reproducible, uniform and directed alpha particle irradiation to investigate the impact of alpha radiation on the cellular level.
Highlights
Understanding the impact of alpha particles on biological material, such as DNA, is of utmost importance to verify and optimize future radionuclide therapy
Using point-source irradiation allows in-depth analysis of double stranded breaks (DSBs) induced by alpha particles while field-irradiation will allow experiments on larger number of cells for colony survival or immunoblotting
A great difficulty for alpha particle irradiation is to assure that every cell has received the same dose
Summary
Understanding the impact of alpha particles on biological material, such as DNA, is of utmost importance to verify and optimize future radionuclide therapy. The exact biological effects of alpha particles, in the context of DNA damage, is still poorly understood. The high linear energy transfer (LET) of alpha particles, compared to betaand gamma- irradiation, induces more cell death, which results in high relative biological effectiveness (RBE) [1]. This effectiveness is due to the short distance between individual ionization caused by alpha particles [2,3]. The highly ionizing path of alpha particles induces clusters of double stranded breaks (DSBs) in the DNA along a straight track (10−20 DSBs per 10 μm track length) [4]. The use of alpha particle emitting radionuclides, conjugated to antibodies or peptides shows
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