title: Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells.
abstract: OBJECTIVE
  Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with (111)In-oxine has been used in preclinical trials. This study aimed to validate (111)In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells.
  
  
  METHODS
  Murine haematopoietic progenitor cells (10(6), FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) (111)In-oxine and compared with unlabelled controls. Cellular retention of (111)In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity.
  
  
  RESULTS
  Labelling efficiency was 75 +/- 14%. Cellular retention of incorporated (111)In after 48 h was 18 +/- 4%. Percentage viability after 48 h was 90 +/- 1% (control), 58 +/- 7% (low dose) and 48 +/- 8% (high dose) (p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 +/- 51% (control), 42 +/- 8% (low dose) and 32 +/- 5% (high dose) (p<0.0001). Cells accumulated in the spleen (86.6 +/- 27.0% ID/g), bone marrow (59.1 +/- 16.1% ID/g) and liver (30.3 +/- 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 +/- 21.8% ID/g) after right ventricular injection.
  
  
  CONCLUSIONS
  Radiolabelling of haematopoietic progenitor cells with (111)In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion.
authors.affiliation: Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. be.nowak@arcor.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Nowak
authors.affiliation: Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.affiliation: Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
authors.affiliation: Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Zeiffer
authors.affiliation: Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.affiliation: Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Hundelshausen
authors.affiliation: Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Reinartz
authors.affiliation: Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Schaefer
authors.affiliation: Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Buell
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000528:radiation effects; D007205:Indium Radioisotopes; D008168:Lung / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives*; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals; D013997:Time Factors
chemical_list: D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C032950:indium oxine; D015125:Oxyquinoline