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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 5/2007

01.05.2007 | Original article

Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells

verfasst von: Bernd Nowak, Christian Weber, Andreas Schober, Ute Zeiffer, Elisa A. Liehn, Philipp von Hundelshausen, Patrick Reinartz, Wolfgang M. Schaefer, Ulrich Buell

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 5/2007

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Abstract

Purpose

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 111In-oxine has been used in preclinical trials. This study aimed to validate 111In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells.

Methods

Murine haematopoietic progenitor cells (106, FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) 111In-oxine and compared with unlabelled controls. Cellular retention of 111In, 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 111In 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.

Conclusion

Radiolabelling of haematopoietic progenitor cells with 111In-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.
Literatur
1.
Zurück zum Zitat Ferrari G, Cusella-De AG, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998;279:1528–30.CrossRefPubMed Ferrari G, Cusella-De AG, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998;279:1528–30.CrossRefPubMed
2.
Zurück zum Zitat Bittner RE, Schofer C, Weipoltshammer K, Ivanova S, Streubel B, Hauser E, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol 1999;199:391–6.CrossRefPubMed Bittner RE, Schofer C, Weipoltshammer K, Ivanova S, Streubel B, Hauser E, et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat Embryol 1999;199:391–6.CrossRefPubMed
3.
Zurück zum Zitat Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999;401:390–4.PubMed Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999;401:390–4.PubMed
4.
Zurück zum Zitat Brazelton TR, Rossi FM, Keshet GI, Blau HM. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000;290:1775–9.CrossRefPubMed Brazelton TR, Rossi FM, Keshet GI, Blau HM. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000;290:1775–9.CrossRefPubMed
5.
Zurück zum Zitat Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000;290:1779–82.CrossRefPubMed Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000;290:1779–82.CrossRefPubMed
6.
Zurück zum Zitat Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–5.CrossRefPubMed Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–5.CrossRefPubMed
7.
Zurück zum Zitat Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell 2001;105:829–41.CrossRefPubMed Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell 2001;105:829–41.CrossRefPubMed
8.
Zurück zum Zitat Kocher AA, Schuster MD, Szabolcs MJ, Burkhoff TD, Wang J, Homma S, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001;7:430–6.CrossRefPubMed Kocher AA, Schuster MD, Szabolcs MJ, Burkhoff TD, Wang J, Homma S, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001;7:430–6.CrossRefPubMed
9.
Zurück zum Zitat Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913–8.CrossRefPubMed Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913–8.CrossRefPubMed
10.
Zurück zum Zitat Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106:3009–17.CrossRefPubMed Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106:3009–17.CrossRefPubMed
11.
Zurück zum Zitat Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141–8.CrossRefPubMed Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141–8.CrossRefPubMed
12.
Zurück zum Zitat Zhang ZG, Zhang L, Jiang Q, Chopp M. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res 2002;90:284–8.CrossRefPubMed Zhang ZG, Zhang L, Jiang Q, Chopp M. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res 2002;90:284–8.CrossRefPubMed
13.
Zurück zum Zitat Shintani S, Murohara T, Ikeda H, Ueno T, Sasaki K, Duan J, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 2001;103:897–903.CrossRefPubMed Shintani S, Murohara T, Ikeda H, Ueno T, Sasaki K, Duan J, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 2001;103:897–903.CrossRefPubMed
14.
Zurück zum Zitat Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 2001;169:12–20.CrossRefPubMed Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 2001;169:12–20.CrossRefPubMed
15.
Zurück zum Zitat Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003;107:2134–9.CrossRefPubMed Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003;107:2134–9.CrossRefPubMed
16.
Zurück zum Zitat Chin BB, Nakamoto Y, Bulte JW, Pittenger MF, Wahl R, Kraitchman DL. 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun 2003;24:1149–54.CrossRefPubMed Chin BB, Nakamoto Y, Bulte JW, Pittenger MF, Wahl R, Kraitchman DL. 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun 2003;24:1149–54.CrossRefPubMed
17.
Zurück zum Zitat Brenner W, Aicher A, Eckey T, Massoudi S, Zuhayra M, Koehl U, et al. 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. J Nucl Med 2004;45:512–8.PubMed Brenner W, Aicher A, Eckey T, Massoudi S, Zuhayra M, Koehl U, et al. 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. J Nucl Med 2004;45:512–8.PubMed
18.
Zurück zum Zitat Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003;107:2290–3.CrossRefPubMed Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003;107:2290–3.CrossRefPubMed
19.
Zurück zum Zitat Wu JC, Chen IY, Sundaresan G, Min JJ, De A, Qiao JH, et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation 2003;108:1302–5.CrossRefPubMedPubMedCentral Wu JC, Chen IY, Sundaresan G, Min JJ, De A, Qiao JH, et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation 2003;108:1302–5.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Becker W. The contribution of nuclear medicine to the patient with infection. Eur J Nucl Med 1995;22:1195–211.CrossRefPubMed Becker W. The contribution of nuclear medicine to the patient with infection. Eur J Nucl Med 1995;22:1195–211.CrossRefPubMed
21.
Zurück zum Zitat Smyth JV, Dodd PD, Walker MG. Indium-111 platelet scintigraphy in vascular disease. Br J Surg 1995;82:588–95.CrossRefPubMed Smyth JV, Dodd PD, Walker MG. Indium-111 platelet scintigraphy in vascular disease. Br J Surg 1995;82:588–95.CrossRefPubMed
22.
Zurück zum Zitat Sharefkin JB, Lather C, Smith M, Rich NM. Endothelial cell labeling with indium-111-oxine as a marker of cell attachment to bioprosthetic surfaces. J Biomed Mater Res 1983;17:345–57.CrossRefPubMed Sharefkin JB, Lather C, Smith M, Rich NM. Endothelial cell labeling with indium-111-oxine as a marker of cell attachment to bioprosthetic surfaces. J Biomed Mater Res 1983;17:345–57.CrossRefPubMed
23.
Zurück zum Zitat Budd JS, Bell PR, James RF. Attachment of indium-111 labelled endothelial cells to pretreated polytetrafluoroethylene vascular grafts. Br J Surg 1989;76:1259–61.CrossRefPubMed Budd JS, Bell PR, James RF. Attachment of indium-111 labelled endothelial cells to pretreated polytetrafluoroethylene vascular grafts. Br J Surg 1989;76:1259–61.CrossRefPubMed
24.
Zurück zum Zitat Bohnen NI, Charron M, Reyes J, Rubinstein W, Strom SC, Swanson D, et al. Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion. Clin Nucl Med 2000;25:447–50.CrossRefPubMed Bohnen NI, Charron M, Reyes J, Rubinstein W, Strom SC, Swanson D, et al. Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion. Clin Nucl Med 2000;25:447–50.CrossRefPubMed
25.
Zurück zum Zitat Eggert AAO, Schreurs MWJ, Boerman OC, Oyen WJC, de Boer AJ, Punt CJA, et al. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 1999;59:3340–5.PubMed Eggert AAO, Schreurs MWJ, Boerman OC, Oyen WJC, de Boer AJ, Punt CJA, et al. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 1999;59:3340–5.PubMed
26.
Zurück zum Zitat Patterson RB, Mayfield G, Silberstein EB, Kempczinski RF. The potential unreliability of indium 111 oxine labeling in studies of endothelial cell kinetics. J Vasc Surg 1989;10:650–5.CrossRefPubMed Patterson RB, Mayfield G, Silberstein EB, Kempczinski RF. The potential unreliability of indium 111 oxine labeling in studies of endothelial cell kinetics. J Vasc Surg 1989;10:650–5.CrossRefPubMed
27.
Zurück zum Zitat Carr HM, Smyth JV, Rooney OB, Dodd PD, Sharma H, Walker MG. Limitations of in-vitro labeling of endothelial cells with indium-111 oxine. Cell Transplant 1995;4:291–6.CrossRefPubMed Carr HM, Smyth JV, Rooney OB, Dodd PD, Sharma H, Walker MG. Limitations of in-vitro labeling of endothelial cells with indium-111 oxine. Cell Transplant 1995;4:291–6.CrossRefPubMed
28.
Zurück zum Zitat Mortelmans L, Verbruggen A, Malbrain S, Heynen MJ, de Bakker C, Boogaerts M, et al. Evaluation of 111In labelled white blood cells by in vitro functional tests and electron microscopy. Comparison of three labelling methods. Eur J Nucl Med 1988;14:159–64.CrossRefPubMed Mortelmans L, Verbruggen A, Malbrain S, Heynen MJ, de Bakker C, Boogaerts M, et al. Evaluation of 111In labelled white blood cells by in vitro functional tests and electron microscopy. Comparison of three labelling methods. Eur J Nucl Med 1988;14:159–64.CrossRefPubMed
29.
Zurück zum Zitat Evans CA, Pierce A, Winter SA, Spooncer E, Heyworth CM, Whetton AD. Activation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development. Blood 1999;94:1504–14.PubMed Evans CA, Pierce A, Winter SA, Spooncer E, Heyworth CM, Whetton AD. Activation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development. Blood 1999;94:1504–14.PubMed
30.
Zurück zum Zitat Zhou R, Thomas DH, Qiao H, Bal HS, Choi SR, Alavi A, et al. In vivo detection of stem cells grafted in infarcted rat myocardium. J Nucl Med 2005;46:816–22.PubMedPubMedCentral Zhou R, Thomas DH, Qiao H, Bal HS, Choi SR, Alavi A, et al. In vivo detection of stem cells grafted in infarcted rat myocardium. J Nucl Med 2005;46:816–22.PubMedPubMedCentral
31.
Zurück zum Zitat Jonsson AC, Jönsson BA, Strand SE, Grafström G, Spanne P. Cell survival after Auger electron emission from stable intracellular indium exposed to monochromatic synchrotron radiation. Acta Oncol 1996;35:947–52.CrossRefPubMed Jonsson AC, Jönsson BA, Strand SE, Grafström G, Spanne P. Cell survival after Auger electron emission from stable intracellular indium exposed to monochromatic synchrotron radiation. Acta Oncol 1996;35:947–52.CrossRefPubMed
32.
Zurück zum Zitat Hendrikx PJ, Martens CM, Hagenbeek A, Keij JF, Visser JW. Homing of fluorescently labeled murine hematopoietic stem cells. Exp Hematol 1996;24:129–40.PubMed Hendrikx PJ, Martens CM, Hagenbeek A, Keij JF, Visser JW. Homing of fluorescently labeled murine hematopoietic stem cells. Exp Hematol 1996;24:129–40.PubMed
33.
Zurück zum Zitat Klonizakis I, Peters AM, Fitzpatrick ML, Kensett MJ, Lewis SM, Lavender JP. Radionuclide distribution following injection of 111Indium-labelled platelets. Br J Haematol 1980;46:595–602.CrossRefPubMed Klonizakis I, Peters AM, Fitzpatrick ML, Kensett MJ, Lewis SM, Lavender JP. Radionuclide distribution following injection of 111Indium-labelled platelets. Br J Haematol 1980;46:595–602.CrossRefPubMed
34.
Zurück zum Zitat Wessels P, Heyns AD, Pieters H, Lotter MG, Badenhorst PN. An improved method for the quantification of the in vivo kinetics of a representative population of 111In-labelled human platelets. Eur J Nucl Med 1985;10:522–7.PubMed Wessels P, Heyns AD, Pieters H, Lotter MG, Badenhorst PN. An improved method for the quantification of the in vivo kinetics of a representative population of 111In-labelled human platelets. Eur J Nucl Med 1985;10:522–7.PubMed
35.
Zurück zum Zitat Peters AM, Saverymuttu SH, Bell RN, Lavender JP. Quantification of the distribution of the marginating granulocyte pool in man. Scand J Haematol 1985;34:111–20.CrossRefPubMed Peters AM, Saverymuttu SH, Bell RN, Lavender JP. Quantification of the distribution of the marginating granulocyte pool in man. Scand J Haematol 1985;34:111–20.CrossRefPubMed
36.
Zurück zum Zitat Saverymuttu SH, Peters AM, Keshavarzian A, Reavy HJ, Lavender JP. The kinetics of 111indium distribution following injection of 111indium labelled autologous granulocytes in man. Br J Haematol 1985;61:675–85.CrossRefPubMed Saverymuttu SH, Peters AM, Keshavarzian A, Reavy HJ, Lavender JP. The kinetics of 111indium distribution following injection of 111indium labelled autologous granulocytes in man. Br J Haematol 1985;61:675–85.CrossRefPubMed
37.
Zurück zum Zitat ICRP Publication 53. Radiation dose to patients from radiopharmaceuticals. Ann ICRP 1988;18:253–6. ICRP Publication 53. Radiation dose to patients from radiopharmaceuticals. Ann ICRP 1988;18:253–6.
38.
Zurück zum Zitat Danpure HJ, Osman S. Cell labelling and cell damage with indium-111 acetylacetone—an alternative to indium 111 oxine. Br J Radiol 1981;54:597–601.CrossRefPubMed Danpure HJ, Osman S. Cell labelling and cell damage with indium-111 acetylacetone—an alternative to indium 111 oxine. Br J Radiol 1981;54:597–601.CrossRefPubMed
39.
Zurück zum Zitat Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003;108:863–8.CrossRefPubMed Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003;108:863–8.CrossRefPubMed
40.
Zurück zum Zitat Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B, et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005;111:2198–202.CrossRefPubMed Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B, et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005;111:2198–202.CrossRefPubMed
41.
Zurück zum Zitat Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004;17:484–99.CrossRefPubMed Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004;17:484–99.CrossRefPubMed
42.
Zurück zum Zitat Bulte JW, Kraitchman DL, Mackay AM, Pittenger MF. Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides. Blood 2004;104:3410–2; author reply 3412–3.CrossRefPubMed Bulte JW, Kraitchman DL, Mackay AM, Pittenger MF. Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides. Blood 2004;104:3410–2; author reply 3412–3.CrossRefPubMed
Metadaten
Titel
Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells
verfasst von
Bernd Nowak
Christian Weber
Andreas Schober
Ute Zeiffer
Elisa A. Liehn
Philipp von Hundelshausen
Patrick Reinartz
Wolfgang M. Schaefer
Ulrich Buell
Publikationsdatum
01.05.2007
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 5/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-006-0275-3

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