Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells.
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.
Nowak
Bernd
B
Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. be.nowak@arcor.de.
Weber
Christian
C
Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
Schober
Andreas
A
Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
Zeiffer
Ute
U
Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
Liehn
Elisa A
EA
Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
von Hundelshausen
Philipp
P
Department of Molecular Cardiovascular Research, University Hospital, RWTH Aachen University, Aachen, Germany.
Reinartz
Patrick
P
Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Schaefer
Wolfgang M
WM
Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Buell
Ulrich
U
Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
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
D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C032950:indium oxine; D015125:Oxyquinoline