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

Journal Article · Wed May 28 00:00:00 EDT 2014 · Mutagenesis

DOI:https://doi.org/10.1093/mutage/geu016· OSTI ID:1196276

Taylor, Kristina ^[1]; Lemon, Jennifer A. ^[2]; Boreham, Douglas R. ^[2]

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1. McMaster Univ., Hamilton, ON (Canada); McMaster University
2. McMaster Univ., Hamilton, ON (Canada)

Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[¹⁸F] fluoro-2-deoxy-d-glucose (¹⁸F-FDG), however little research has been conducted on the biological effects of ¹⁸F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from ¹⁸F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from ¹⁸F-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 ¹⁸F-FDG, mice were injected with a range of activities of ¹⁸F-FDG (0–14.80 MBq) or irradiated with Cs-137 γ-rays (0–100 mGy). The adaptive response was investigated 24 h after the ¹⁸F-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 ¹⁸F-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 ¹⁸F-FDG relative to controls (P < 0.019). A 0.74 MBq ¹⁸F-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 ¹⁸F-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. Lastly, the ¹⁸F-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.

• Research Organization: McMaster Univ., Hamilton, ON (Canada)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
• Grant/Contract Number: FG02-07ER64343
• OSTI ID: 1196276
• Report Number(s): DOE-MAC--64343
• Journal Information: Mutagenesis, Journal Name: Mutagenesis Journal Issue: 4 Vol. 29; ISSN 0267-8357
• Publisher: Oxford University Press
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
PET scan
cancer risk
low dose radiation
radiation-induced damage