title: Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing ¹⁸F-FDG PET/CT examinations.
abstract: OBJECTIVE
  The purpose of this study was to evaluate DNA double-strand breaks (DSBs) in blood lymphocytes of patients undergoing positron emission tomography (PET)/CT using γ-H2AX immunofluorescence microscopy and to differentiate between (18)F-fluorodeoxyglucose (FDG) and CT-induced DNA lesions.
  
  
  METHODS
  This study was approved by the local Ethics Committee and complies with Health Insurance Portability and Accountability Act (HIPAA) requirements. After written informed consent was obtained, 33 patients underwent whole-body (18)F-FDG PET/CT (3 MBq/kg body weight, 170/100 reference mAs at 120 kV). The FDG PET and CT portions were performed as an initial CT immediately followed by the PET. Blood samples were obtained before, at various time points following (18)F-FDG application and up to 24 h after the CT scan. Distinct foci representing DSBs were quantified in isolated lymphocytes using fluorescence microscopy after staining against the phosphorylated histone variant γ-H2AX.
  
  
  RESULTS
  The DSB values at the various time points were significantly different (p < 0.001). The median baseline level was 0.08/cell (range 0.06-0.12/cell). Peaks of radiation-induced DSBs were found 30 min after (18)F-FDG administration (median excess foci 0.11/cell, range 0.06-0.27/cell) and 5 min after CT (median excess foci 0.17/cell, range 0.05-0.54/cell). A significant correlation between CT-induced DSBs and dose length product was obtained (ρ = 0.898, p < 0.001). After 24 h DSB values were still slightly but significantly elevated (median foci 0.11/cell, range 0.10-0.14/cell, p = 0.003) compared to pre-exposure levels.
  
  
  CONCLUSIONS
  PET/CT-induced DSBs can be monitored using γ-H2AX immunofluorescence microscopy. Peak values may be obtained 30 min after (18)F-FDG injection and 5 min after CT. The radionuclide contributes considerably to the total DSB induction in this setting.
authors.affiliation: Department of Radiology, University Hospital Erlangen, Erlangen, Germany. matthias.may@uk-erlangen.de
authors.forename: Matthias S
authors.initials: MS
authors.lastname: May
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wuest
authors.forename: Katharina
authors.initials: K
authors.lastname: Anders
authors.forename: Torsten
authors.initials: T
authors.lastname: Kuwert
authors.forename: Olaf
authors.initials: O
authors.lastname: Prante
authors.forename: Daniela
authors.initials: D
authors.lastname: Schmidt
authors.forename: Simone
authors.initials: S
authors.lastname: Maschauer
authors.forename: Richard C
authors.initials: RC
authors.lastname: Semelka
authors.forename: Michael
authors.initials: M
authors.lastname: Uder
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuefner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005260:Female; D019788:Fluorodeoxyglucose F18; D006657:Histones / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D064847:Multimodal Imaging; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed
chemical_list: D006657:Histones; D019788:Fluorodeoxyglucose F18