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

Abstract

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 =more » 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.« less

Authors:

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

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+ Show Author Affiliations

1. McMaster Univ., Hamilton, ON (Canada)

Publication Date:

Wed May 28 00:00:00 EDT 2014

Research Org.:

McMaster Univ., Hamilton, ON (Canada)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER)

OSTI Identifier:

1196276

Report Number(s):

DOE-MAC-64343
Journal ID: ISSN 0267-8357

Grant/Contract Number:  

FG02-07ER64343

Resource Type:

Accepted Manuscript

Journal Name:

Mutagenesis

Additional Journal Information:

Journal Volume: 29; Journal Issue: 4; Journal ID: ISSN 0267-8357

Publisher:

Oxford University Press

Country of Publication:

United States

Language:

English

Subject:

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