Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice

Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG), however little research has been conducted on the biological effects of (18)F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from (18)F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from (18)F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of (18)F-FDG, mice were injected with a range of activities of (18)F-FDG (0-14.80 MBq) or irradiated with Cs-137 γ-rays (0-100 mGy). The adaptive response was investigated 24h after the (18)F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the (18)F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq (18)F-FDG relative to controls (P < 0.019). A 0.74 MBq (18)F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical (18)F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation, below spontaneous levels observed in control mice. The (18)F-FDG RBE was <1.0, indicating that the mixed radiation quality and/or low dose rate from PET scans is less damaging than equivalent doses of gamma radiation.