title: DNA damage in blood lymphocytes in patients after (177)Lu peptide receptor radionuclide therapy.
abstract: OBJECTIVE
  The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with (177)Lu-labelled DOTATATE/DOTATOC.
  
  
  METHODS
  The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with (131)I and (177)Lu.
  
  
  RESULTS
  The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair.
  
  
  CONCLUSIONS
  Measurements of RIF and the absorbed dose to the blood after systemic administration of (177)Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair.
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. eberlein_u@klinik.uni-wuerzburg.de.
authors.forename: Uta
authors.initials: U
authors.lastname: Eberlein
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, 80937, Munich, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Nowak
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bluemel
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Andreas Konrad
authors.initials: AK
authors.lastname: Buck
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Rudolf Alexander
authors.initials: RA
authors.lastname: Werner
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, 80937, Munich, Germany.
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lassmann
mesh_terms: D000368:Aged; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use*; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000097:blood / Q000235:genetics*; D011868:Radioisotopes / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D018000:Receptors, Peptide / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011868:Radioisotopes; D018000:Receptors, Peptide; D008187:Lutetium