title: Quantifying murine bone marrow and blood radiation dose response following (18)F-FDG PET with DNA damage biomarkers.
abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ((18)F)-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 (18)F-FDG: 0-37MBq or whole body irradiated with corresponding doses of 0-300mGy X-rays. Blood samples were collected at 24h and at 43h 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 (18)F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43mGy and above for internal (18)F-FDG exposure and to 25mGy 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 24h for Bbc3 and Cdkn1 were similar for (18)F-FDG and X-ray exposures, with significant modifications occurring for doses over 300mGy for Bbc3 and at the lower dose of 150mGy 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 (18)F-FDG PET.
authors.affiliation: Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ, UK.
authors.forename: Grainne
authors.initials: G
authors.lastname: Manning
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Kristina
authors.initials: K
authors.lastname: Taylor
authors.affiliation: Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Finnon
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lemon
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Boreham
authors.affiliation: Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ, UK. Electronic address: christophe.badie@phe.gov.uk.
authors.forename: Christophe
authors.initials: C
authors.lastname: Badie
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism / Q000528:radiation effects*; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000009:adverse effects* / Q000493:pharmacokinetics; D015870:Gene Expression / Q000528:radiation effects; D005819:Genetic Markers / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D016273:Occupational Exposure / Q000032:analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D049268:Positron-Emission Tomography / Q000009:adverse effects*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D005819:Genetic Markers; D019788:Fluorodeoxyglucose F18
keywords: (18)F-FDG/positron emission tomography; Biomarkers; DNA damage; Dose–response; Gene expression; MN-RET