Quantifying murine bone marrow and blood radiation dose response following 18FFDG PET with DNA damage biomarkers

The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 (F-18)-fluorodeoxyglucose (FDG) positron emission tomography( PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3-5 mice were randomly assigned to 10 groups, each receiving either a different activity of F-18-FDG:0-37 MBq or whole body irradiated with corresponding doses of 0-300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of F-18-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal F-18-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls( P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R-2 of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose-responses at 24 h for Bbc3 and Cdkn1 were similar for F-18-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3 and at the lower dose of 150 mGy for Cdkn1a. Both leucocyte gene expression and quantification of MN-RET are highly sensitive biomarkers for reliable estimation of the low doses delivered in vivo to, respectively, blood and bone marrow, following F-18-FDGPET. (C) 2014 Elsevier B.V. All rights reserved.