Skip to main content

Advertisement

Log in

Radiolabeling Strategies for Radionuclide Imaging of Stem Cells

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

The interest in the use of stem cells as a source for therapy has increased dramatically over the last decades. Different stem cell types have been tested in both in vitro and in vivo models, because of their properties such as differentiation potential, trophic effects and immune modulatory properties. To further optimize the use of different stem cell types for the treatment of disease in a clinical setting, it is necessary to know more about the in vivo behavior of these cells following engraftment. Until now, the golden standard to preclinically evaluate cell therapy was histology, which is an invasive method as the animals need to be sacrificed. This hampers the generation of dynamic information and results in only one single point in time available for analysis per animal. For more information regarding cell migration, in situ persistence, viability, proliferation and differentiation, molecular imaging can be used for imaging cells after transplantation dynamically and longitudinally, in a noninvasive way. With this technology, it becomes possible to track cells within the same subjects over a long period of time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15

Similar content being viewed by others

References

  1. Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., et al. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet, 371(9624), 1579–86.

    PubMed  Google Scholar 

  2. Sohni, A., & Verfaillie, C. M. (2011). Multipotent adult progenitor cells. Best Practice & Research Clinical Haematology, 24(1), 3–11.

    CAS  Google Scholar 

  3. Cao, Y. A., Wagers, A. J., Beilhack, A., Dusich, J., Bachmann, M. H., Negrin, R. S., et al. (2004). Shifting foci of hematopoiesis during reconstitution from single stem cells. Proceedings of the National Academy of Sciences of the United States of America, 101(1), 221–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Reumers, V., Deroose, C. M., Krylyshkina, O., Nuyts, J., Geraerts, M., Mortelmans, L., et al. (2008). Noninvasive and quantitative monitoring of adult neuronal stem cell migration in mouse brain using bioluminescence imaging. Stem Cells, 26(9), 2382–90.

    PubMed  Google Scholar 

  5. Jacobs, R. E., & Cherry, S. R. (2001). Complementary emerging techniques: high-resolution PET and MRI. Current Opinion in Neurobiology, 11(5), 621–9.

    CAS  PubMed  Google Scholar 

  6. Phelps, M. E., Hoffman, E. J., Mullani, N. A., & Ter-Pogossian, M. M. (1975). Application of annihilation coincidence detection to transaxial reconstruction tomography. Journal of Nuclear Medicine, 16(3), 210–24.

    CAS  PubMed  Google Scholar 

  7. Vastenhouw, B., & Beekman, F. (2007). Submillimeter total-body murine imaging with U-SPECT-I. Journal of Nuclear Medicine, 48(3), 487–93.

    PubMed  Google Scholar 

  8. Jones, T., & Rabiner, E. A. (2012). The development, past achievements, and future directions of brain PET. Journal of Cerebral Blood Flow and Metabolism, 32(7), 1426–54.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Krause, B. J., Schwarzenbock, S., & Souvatzoglou, M. (2013). FDG PET and PET/CT. Recent Results in Cancer Research, 187, 351–69.

    CAS  PubMed  Google Scholar 

  10. Paterson, D. I., OMeara, E., Chow, B. J., Ukkonen, H., & Beanlands, R. S. (2011). Recent advances in cardiac imaging for patients with heart failure. Current Opinion in Cardiology, 26(2), 132–43.

    PubMed  Google Scholar 

  11. Bhargava, K. K., Gupta, R. K., Nichols, K. J., & Palestro, C. J. (2009). In vitro human leukocyte labeling with (64) Cu: an intraindividual comparison with (111) in-oxine and (18) F-FDG. Nuclear Medicine and Biology, 36(5), 545–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Doyle, B., Kemp, B. J., Chareonthaitawee, P., Reed, C., Schmeckpeper, J., Sorajja, P., et al. (2007). Dynamic tracking during intracoronary injection of 18F-FDG-labeled progenitor cell therapy for acute myocardial infarction. Journal of Nuclear Medicine, 48(10), 1708–14.

    PubMed  Google Scholar 

  13. Elhami, E., Goertzen, A. L., Xiang, B., Deng, J., Stillwell, C., Mzengeza, S., et al. (2011). Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer. European Journal of Nuclear Medicine and Molecular Imaging, 38(7), 1323–34.

    CAS  PubMed  Google Scholar 

  14. Zhang, Y., Thorn, S., DaSilva, J. N., Lamoureux, M., DeKemp, R. A., Beanlands, R. S., et al. (2008). Collagen-based matrices improve the delivery of transplanted circulating progenitor cells: development and demonstration by ex vivo radionuclide cell labeling and in vivo tracking with positron-emission tomography. Circulation. Cardiovascular Imaging, 1(3), 197–204.

    CAS  PubMed  Google Scholar 

  15. Chen, M. F., Lin, C. T., Chen, W. C., Yang, C. T., Chen, C. C., Liao, S. K., et al. (2006). The sensitivity of human mesenchymal stem cells to ionizing radiation. International Journal of Radiation Oncology, Biology, and Physics, 66(1), 244–53.

    CAS  Google Scholar 

  16. Wolfs, E., Struys, T., Notelaers, T., Roberts, S. J., Sohni, A., Bormans, G., et al. (2013). 18F-FDG labeling of mesenchymal stem cells and multipotent adult progenitor cells for PET imaging: effects on ultrastructure and differentiation capacity. Journal of Nuclear Medicine, 54(3), 447–54.

    CAS  PubMed  Google Scholar 

  17. Hofmann, M., Wollert, K. C., Meyer, G. P., Menke, A., Arseniev, L., Hertenstein, B., et al. (2005). Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 111(17), 2198–202.

    PubMed  Google Scholar 

  18. Kang, W. J., Kang, H. J., Kim, H. S., Chung, J. K., Lee, M. C., & Lee, D. S. (2006). Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. Journal of Nuclear Medicine, 47(8), 1295–301.

    PubMed  Google Scholar 

  19. Thakur, M. L., Segal, A. W., Louis, L., Welch, M. J., Hopkins, J., & Peters, T. J. (1977). Indium-111-labeled cellular blood components: mechanism of labeling and intracellular location in human neutrophils. Journal of Nuclear Medicine, 18(10), 1022–6.

    CAS  PubMed  Google Scholar 

  20. Horcajada, J. P., Gutierrez-Cuadra, M., Martinez-Rodriguez, I., Salas, C., Parra, J. A., Benito, N., et al. (2012). High prevalence of upper urinary tract involvement detected by 111indium-oxine leukocyte scintigraphy in patients with candiduria. European Journal of Clinical Microbiology & Infectious Diseases, 31(3), 237–42.

    CAS  Google Scholar 

  21. Chin, B. B., Nakamoto, Y., Bulte, J. W., Pittenger, M. F., Wahl, R., & Kraitchman, D. L. (2003). 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nuclear Medicine Communications, 24(11), 1149–54.

    CAS  PubMed  Google Scholar 

  22. Brenner, W., Aicher, A., Eckey, T., Massoudi, S., Zuhayra, M., Koehl, U., et al. (2004). 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. Journal of Nuclear Medicine, 45(3), 512–8.

    CAS  PubMed  Google Scholar 

  23. Nowak, B., Weber, C., Schober, A., Zeiffer, U., Liehn, E. A., von Hundelshausen, P., et al. (2007). Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells. European Journal of Nuclear Medicine and Molecular Imaging, 34(5), 715–21.

    CAS  PubMed  Google Scholar 

  24. Mitkari, B., Kerkela, E., Nystedt, J., Korhonen, M., Mikkonen, V., Huhtala, T., et al. (2013). Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats. Experimental Neurology, 239, 158–62.

    CAS  PubMed  Google Scholar 

  25. Kraitchman, D. L., Tatsumi, M., Gilson, W. D., Ishimori, T., Kedziorek, D., Walczak, P., et al. (2005). Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation, 112(10), 1451–61.

    PubMed Central  PubMed  Google Scholar 

  26. Gholamrezanezhad, A., Mirpour, S., Bagheri, M., Mohamadnejad, M., Alimoghaddam, K., Abdolahzadeh, L., et al. (2011). In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nuclear Medicine and Biology, 38(7), 961–7.

    CAS  PubMed  Google Scholar 

  27. Schots, R., De Keulenaer, G., Schoors, D., Caveliers, V., Dujardin, M., Verheye, S., et al. (2007). Evidence that intracoronary-injected CD133+ peripheral blood progenitor cells home to the myocardium in chronic postinfarction heart failure. Experimental Hematology, 35(12), 1884–90.

    CAS  PubMed  Google Scholar 

  28. Caveliers, V., De Keulenaer, G., Everaert, H., Van Riet, I., Van Camp, G., Verheye, S., et al. (2007). In vivo visualization of 111In labeled CD133+ peripheral blood stem cells after intracoronary administration in patients with chronic ischemic heart disease. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 51(1), 61–6.

    CAS  PubMed  Google Scholar 

  29. Jorgensen, C., Couret, I., Bologna, C., Rossi, M., & Sany, J. (1995). Radiolabelled lymphocyte migration in rheumatoid synovitis. Annals of the Rheumatic Diseases, 54(1), 39–44.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Detante, O., Moisan, A., Dimastromatteo, J., Richard, M. J., Riou, L., Grillon, E., et al. (2009). Intravenous administration of 99mTc-HMPAO-labeled human mesenchymal stem cells after stroke: in vivo imaging and biodistribution. Cell Transplantation, 18(12), 1369–79.

    PubMed  Google Scholar 

  31. Park, B. N., Shim, W., Lee, G., Bang, O. Y., An, Y. S., Yoon, J. K., et al. (2011). Early distribution of intravenously injected mesenchymal stem cells in rats with acute brain trauma evaluated by (99 m) Tc-HMPAO labeling. Nuclear Medicine and Biology, 38(8), 1175–82.

    CAS  PubMed  Google Scholar 

  32. Goussetis, E., Manginas, A., Koutelou, M., Peristeri, I., Theodosaki, M., Kollaros, N., et al. (2006). Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution. Stem Cells, 24(10), 2279–83.

    CAS  PubMed  Google Scholar 

  33. Kollaros, N., Theodorakos, A., Manginas, A., Kitziri, E., Katsikis, A., Cokkinos, D., et al. (2012). Bone marrow stem cell adherence into old anterior myocardial infarction: a scintigraphic study using Tl-201 and Tc-99 m-HMPAO. Annals of Nuclear Medicine, 26(3), 228–33.

    PubMed  Google Scholar 

  34. Tarantal, A. F., Lee, C. C., Batchelder, C. A., Christensen, J. E., Prater, D., & Cherry, S. R. (2012). Radiolabeling and in vivo imaging of transplanted renal lineages differentiated from human embryonic stem cells in fetal rhesus monkeys. Molecular Imaging and Biology, 14(2), 197–204.

    PubMed Central  PubMed  Google Scholar 

  35. Ma, B., Hankenson, K. D., Dennis, J. E., Caplan, A. I., Goldstein, S. A., & Kilbourn, M. R. (2005). A simple method for stem cell labeling with fluorine 18. Nuclear Medicine and Biology, 32(7), 701–5.

    CAS  PubMed  Google Scholar 

  36. Zhang, Y., Dasilva, J. N., Hadizad, T., Thorn, S., Kuraitis, D., Renaud, J. M., et al. (2012). (18) F-FDG cell labeling may underestimate transplanted cell homing: more accurate, efficient and stable cell labeling with hexadecyl-4-[(18) F] fluorobenzoate for in vivo tracking of transplanted human progenitor cells by positron emission tomography. Cell Transplantation, 21, 1821–35.

    PubMed  Google Scholar 

  37. Gambhir, S. S., Herschman, H. R., Cherry, S. R., Barrio, J. R., Satyamurthy, N., Toyokuni, T., et al. (2000). Imaging transgene expression with radionuclide imaging technologies. Neoplasia, 2(1–2), 118–38.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. De, A., Lewis, X. Z., & Gambhir, S. S. (2003). Noninvasive imaging of lentiviral-mediated reporter gene expression in living mice. Molecular Therapy, 7(5 Pt 1), 681–91.

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Schipper, M. L., & Gambhir, S. S. (2000). Imaging Gene Expression: Concepts and Future Outlook. In C. Schiepers (Ed.), Diagnostic nuclear medicine (pp. p. 253–72). Berlin: Springer.

    Google Scholar 

  40. Li, Z., Dullmann, J., Schiedlmeier, B., Schmidt, M., von Kalle, C., Meyer, J., et al. (2002). Murine leukemia induced by retroviral gene marking. Science, 296(5567), 497.

    CAS  PubMed  Google Scholar 

  41. Bushman, F., Lewinski, M., Ciuffi, A., Barr, S., Leipzig, J., Hannenhalli, S., et al. (2005). Genome-wide analysis of retroviral DNA integration. Nature Reviews Microbiology, 3(11), 848–58.

    CAS  PubMed  Google Scholar 

  42. Schroder, A. R., Shinn, P., Chen, H., Berry, C., Ecker, J. R., & Bushman, F. (2002). HIV-1 integration in the human genome favors active genes and local hotspots. Cell, 110(4), 521–9.

    CAS  PubMed  Google Scholar 

  43. Ellis, J. (2005). Silencing and variegation of gammaretrovirus and lentivirus vectors. Human Gene Therapy, 16(11), 1241–6.

    CAS  PubMed  Google Scholar 

  44. Hockemeyer, D., Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., et al. (2009). Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nature Biotechnology, 27(9), 851–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Kotin, R. M., Linden, R. M., & Berns, K. I. (1992). Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO Journal, 11(13), 5071–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Tan, I., Ng, C. H., Lim, L., & Leung, T. (2001). Phosphorylation of a novel myosin binding subunit of protein phosphatase 1 reveals a conserved mechanism in the regulation of actin cytoskeleton. The Journal of Biological Chemistry, 276(24), 21209–16.

    CAS  PubMed  Google Scholar 

  47. Smith, J. R., Maguire, S., Davis, L. A., Alexander, M., Yang, F., Chandran, S., et al. (2008). Robust, persistent transgene expression in human embryonic stem cells is achieved with AAVS1-targeted integration. Stem Cells, 26(2), 496–504.

    CAS  PubMed  Google Scholar 

  48. DeKelver, R. C., Choi, V. M., Moehle, E. A., Paschon, D. E., Hockemeyer, D., Meijsing, S. H., et al. (2010). Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome. Genome Research, 20(8), 1133–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Wang, Y., Zhang, W. Y., Hu, S., Lan, F., Lee, A. S., Huber, B., et al. (2012). Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging. Circulation Research, 111(12), 1494–503.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Filbin, M. E., & Kieft, J. S. (2009). Toward a structural understanding of IRES RNA function. Current Opinion in Structural Biology, 19(3), 267–76.

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Ibrahimi, A., Vande Velde, G., Reumers, V., Toelen, J., Thiry, I., Vandeputte, C., et al. (2009). Highly efficient multicistronic lentiviral vectors with peptide 2A sequences. Human Gene Therapy, 20(8), 845–60.

    CAS  PubMed  Google Scholar 

  52. Ahn, B. C. (2012). Sodium iodide symporter for nuclear molecular imaging and gene therapy: from bedside to bench and back. Theranostics, 2(4), 392–402.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Rath, P., Shi, H., Maruniak, J. A., Litofsky, N. S., Maria, B. L., & Kirk, M. D. (2009). Stem cells as vectors to deliver HSV/tk gene therapy for malignant gliomas. Current Stem Cell Research & Therapy, 4(1), 44–9.

    CAS  Google Scholar 

  54. Deroose, C. M., Reumers, V., Debyser, Z., & Baekelandt, V. (2009). Seeing genes at work in the living brain with non-invasive molecular imaging. Current Gene Therapy, 9(3), 212–38.

    CAS  PubMed  Google Scholar 

  55. Serganova, I., Ponomarev, V., & Blasberg, R. (2007). Human reporter genes: potential use in clinical studies. Nuclear Medicine and Biology, 34(7), 791–807.

    CAS  PubMed  Google Scholar 

  56. Yaghoubi, S. S., Campbell, D. O., Radu, C. G., & Czernin, J. (2012). Positron emission tomography reporter genes and reporter probes: gene and cell therapy applications. Theranostics, 2(4), 374–91.

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Immonen, A., Vapalahti, M., Tyynela, K., Hurskainen, H., Sandmair, A., Vanninen, R., et al. (2004). AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study. Molecular Therapy, 10(5), 967–72.

    CAS  PubMed  Google Scholar 

  58. Valery, C. A., Seilhean, D., Boyer, O., Marro, B., Hauw, J. J., Kemeny, J. L., et al. (2002). Long-term survival after gene therapy for a recurrent glioblastoma. Neurology, 58(7), 1109–12.

    CAS  PubMed  Google Scholar 

  59. Tjuvajev, J. G., Avril, N., Oku, T., Sasajima, T., Miyagawa, T., Joshi, R., et al. (1998). Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Research, 58(19), 4333–41.

    CAS  PubMed  Google Scholar 

  60. Yaghoubi, S., Barrio, J. R., Dahlbom, M., Iyer, M., Namavari, M., Satyamurthy, N., et al. (2001). Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. Journal of Nuclear Medicine, 42(8), 1225–34.

    CAS  PubMed  Google Scholar 

  61. Jacobs, A., Braunlich, I., Graf, R., Lercher, M., Sakaki, T., Voges, J., et al. (2001). Quantitative kinetics of [124I] FIAU in cat and man. Journal of Nuclear Medicine, 42(3), 467–75.

    CAS  PubMed  Google Scholar 

  62. Culver, K. W., Ram, Z., Wallbridge, S., Ishii, H., Oldfield, E. H., & Blaese, R. M. (1992). In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science, 256(5063), 1550–2.

    CAS  PubMed  Google Scholar 

  63. Li, S., Tokuyama, T., Yamamoto, J., Koide, M., Yokota, N., & Namba, H. (2005). Bystander effect-mediated gene therapy of gliomas using genetically engineered neural stem cells. Cancer Gene Therapy, 12(7), 600–7.

    CAS  PubMed  Google Scholar 

  64. Matuskova, M., Hlubinova, K., Pastorakova, A., Hunakova, L., Altanerova, V., Altaner, C., et al. (2010). HSV-tk expressing mesenchymal stem cells exert bystander effect on human glioblastoma cells. Cancer Letters, 290(1), 58–67.

    CAS  PubMed  Google Scholar 

  65. Love, Z., Wang, F., Dennis, J., Awadallah, A., Salem, N., Lin, Y., et al. (2007). Imaging of mesenchymal stem cell transplant by bioluminescence and PET. Journal of Nuclear Medicine, 48(12), 2011–20.

    PubMed  Google Scholar 

  66. Miletic, H., Fischer, Y., Litwak, S., Giroglou, T., Waerzeggers, Y., Winkeler, A., et al. (2007). Bystander killing of malignant glioma by bone marrow-derived tumor-infiltrating progenitor cells expressing a suicide gene. Molecular Therapy, 15(7), 1373–81.

    CAS  PubMed  Google Scholar 

  67. Cao, F., Drukker, M., Lin, S., Sheikh, A. Y., Xie, X., Li, Z., et al. (2007). Molecular imaging of embryonic stem cell misbehavior and suicide gene ablation. Cloning and Stem Cells, 9(1), 107–17.

    CAS  PubMed  Google Scholar 

  68. Perin, E. C., Tian, M., Marini, F. C., 3rd, Silva, G. V., Zheng, Y., Baimbridge, F., et al. (2011). Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model. PloS One, 6(9), e22949.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Ram, Z., Culver, K. W., Oshiro, E. M., Viola, J. J., DeVroom, H. L., Otto, E., et al. (1997). Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nature Medicine, 3(12), 1354–61.

    CAS  PubMed  Google Scholar 

  70. Jacobs, A., Voges, J., Reszka, R., Lercher, M., Gossmann, A., Kracht, L., et al. (2001). Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet, 358(9283), 727–9.

    CAS  PubMed  Google Scholar 

  71. Penuelas, I., Mazzolini, G., Boan, J. F., Sangro, B., Marti-Climent, J., Ruiz, M., et al. (2005). Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients. Gastroenterology, 128(7), 1787–95.

    CAS  PubMed  Google Scholar 

  72. Yaghoubi, S. S., Jensen, M. C., Satyamurthy, N., Budhiraja, S., Paik, D., Czernin, J., et al. (2009). Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nature Clinical Practice Oncology, 6(1), 53–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Riddell, S. R., Elliott, M., Lewinsohn, D. A., Gilbert, M. J., Wilson, L., Manley, S. A., et al. (1996). T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nature Medicine, 2(2), 216–23.

    CAS  PubMed  Google Scholar 

  74. Verzeletti, S., Bonini, C., Marktel, S., Nobili, N., Ciceri, F., Traversari, C., et al. (1998). Herpes simplex virus thymidine kinase gene transfer for controlled graft-versus-host disease and graft-versus-leukemia: clinical follow-up and improved new vectors. Human Gene Therapy, 9(15), 2243–51.

    CAS  PubMed  Google Scholar 

  75. Eriksson, S., Munch-Petersen, B., Johansson, K., & Eklund, H. (2002). Structure and function of cellular deoxyribonucleoside kinases. Cellular and Molecular Life Sciences, 59(8), 1327–46.

    CAS  PubMed  Google Scholar 

  76. Al-Madhoun, A. S., Tjarks, W., & Eriksson, S. (2004). The role of thymidine kinases in the activation of pyrimidine nucleoside analogues. Mini Reviews in Medicinal Chemistry, 4(4), 341–50.

    CAS  PubMed  Google Scholar 

  77. Wang, J., & Eriksson, S. (1996). Phosphorylation of the anti-hepatitis B nucleoside analog 1-(2′-deoxy-2′-fluoro-1-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) by human cytosolic and mitochondrial thymidine kinase and implications for cytotoxicity. Antimicrobial Agents and Chemotherapy, 40(6), 1555–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Wang, J., Su, C., Neuhard, J., & Eriksson, S. (2000). Expression of human mitochondrial thymidine kinase in Escherichia coli: correlation between the enzymatic activity of pyrimidine nucleoside analogues and their inhibitory effect on bacterial growth. Biochemical Pharmacology, 59(12), 1583–8.

    CAS  PubMed  Google Scholar 

  79. Deroose, C. M., Chitneni, S. K., Gijsbers, R., Vermaelen, P., Ibrahimi, A., Balzarini, J., et al. (2012). Preliminary validation of varicella zoster virus thymidine kinase as a novel reporter gene for PET. Nuclear Medicine and Biology, 39(8), 1266–74.

    CAS  PubMed  Google Scholar 

  80. Chitneni, S. K., Deroose, C. M., Balzarini, J., Gijsbers, R., Celen, S., Debyser, Z., et al. (2007). A p-[18F] fluoroethoxyphenyl bicyclic nucleoside analogue as a potential positron emission tomography imaging agent for varicella-zoster virus thymidine kinase gene expression. Journal of Medicinal Chemistry, 50(26), 6627–37.

    CAS  PubMed  Google Scholar 

  81. Eberling, J. L., Cunningham, J., Pivirotto, P., Bringas, J., Daadi, M. M., & Bankiewicz, K. S. (2003). In vivo PET imaging of gene expression in Parkinsonian monkeys. Molecular Therapy, 8(6), 873–5.

    CAS  PubMed  Google Scholar 

  82. Qin, C., Cheng, K., Chen, K., Hu, X., Liu, Y., Lan, X., et al. (2013). Tyrosinase as a multifunctional reporter gene for Photoacoustic/MRI/PET triple modality molecular imaging. Scientific Reports, 3, 1490.

    PubMed Central  PubMed  Google Scholar 

  83. Bunzow, J. R., Van Tol, H. H., Grandy, D. K., Albert, P., Salon, J., Christie, M., et al. (1988). Cloning and expression of a rat D2 dopamine receptor cDNA. Nature, 336(6201), 783–7.

    CAS  PubMed  Google Scholar 

  84. Strange, P. G. (1990). Aspects of the structure of the D2 dopamine receptor. Trends in Neurosciences, 13(9), 373–8.

    CAS  PubMed  Google Scholar 

  85. Liang, Q., Satyamurthy, N., Barrio, J. R., Toyokuni, T., Phelps, M. P., Gambhir, S. S., et al. (2001). Noninvasive, quantitative imaging in living animals of a mutant dopamine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction. Gene Therapy, 8(19), 1490–8.

    CAS  PubMed  Google Scholar 

  86. Chen, I. Y., Wu, J. C., Min, J. J., Sundaresan, G., Lewis, X., Liang, Q., et al. (2004). Micro-positron emission tomography imaging of cardiac gene expression in rats using bicistronic adenoviral vector-mediated gene delivery. Circulation, 109(11), 1415–20.

    PubMed Central  PubMed  Google Scholar 

  87. Hwang do, W., Kang, J. H., Chang, Y. S., Jeong, J. M., Chung, J. K., Lee, M. C., et al. (2007). Development of a dual membrane protein reporter system using sodium iodide symporter and mutant dopamine D2 receptor transgenes. Journal of Nuclear Medicine, 48(4), 588–95.

    PubMed  Google Scholar 

  88. Bousquet, C., Puente, E., Buscail, L., Vaysse, N., & Susini, C. (2001). Antiproliferative effect of somatostatin and analogs. Chemotherapy, 47(Suppl 2), 30–9.

    CAS  PubMed  Google Scholar 

  89. Reubi, J. C., Kvols, L., Krenning, E., & Lamberts, S. W. (1990). Distribution of somatostatin receptors in normal and tumor tissue. Metabolism, 39(9 Suppl 2), 78–81.

    CAS  PubMed  Google Scholar 

  90. Forrer, F., Valkema, R., Kwekkeboom, D. J., de Jong, M., & Krenning, E. P. (2007). Neuroendocrine tumors. Peptide receptor radionuclide therapy. Best Practice & Research Clinical Endocrinology & Metabolism, 21(1), 111–29.

    CAS  Google Scholar 

  91. Ginj, M., Zhang, H., Waser, B., Cescato, R., Wild, D., Wang, X., et al. (2006). Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proceedings of the National Academy of Sciences of the United States of America, 103(44), 16436–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Parry, J. J., Chen, R., Andrews, R., Lears, K. A., & Rogers, B. E. (2012). Identification of critical residues involved in ligand binding and G protein signaling in human somatostatin receptor subtype 2. Endocrinology, 153(6), 2747–55.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Rogers, B. E., Chaudhuri, T. R., Reynolds, P. N., Della Manna, D., & Zinn, K. R. (2003). Non-invasive gamma camera imaging of gene transfer using an adenoviral vector encoding an epitope-tagged receptor as a reporter. Gene Therapy, 10(2), 105–14.

    CAS  PubMed  Google Scholar 

  94. Rogers, B. E., McLean, S. F., Kirkman, R. L., Della Manna, D., Bright, S. J., Olsen, C. C., et al. (1999). In vivo localization of [(111)In]-DTPA-D-Phe1-octreotide to human ovarian tumor xenografts induced to express the somatostatin receptor subtype 2 using an adenoviral vector. Clinical Cancer Research, 5(2), 383–93.

    CAS  PubMed  Google Scholar 

  95. Chaudhuri, T. R., Rogers, B. E., Buchsbaum, D. J., Mountz, J. M., & Zinn, K. R. (2001). A noninvasive reporter system to image adenoviral-mediated gene transfer to ovarian cancer xenografts. Gynecologic Oncology, 83(2), 432–8.

    CAS  PubMed  Google Scholar 

  96. Zinn, K. R., Buchsbaum, D. J., Chaudhuri, T. R., Mountz, J. M., Grizzle, W. E., & Rogers, B. E. (2000). Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with 99mTc or 188Re. Journal of Nuclear Medicine, 41(5), 887–95.

    CAS  PubMed  Google Scholar 

  97. Singh, S. P., Yang, D., Ravoori, M., Han, L., & Kundra, V. (2009). In vivo functional and anatomic imaging for assessment of in vivo gene transfer. Radiology, 252(3), 763–71.

    PubMed Central  PubMed  Google Scholar 

  98. Cotugno, G., Aurilio, M., Annunziata, P., Capalbo, A., Faella, A., Rinaldi, V., et al. (2011). Noninvasive repetitive imaging of somatostatin receptor 2 gene transfer with positron emission tomography. Human Gene Therapy, 22(2), 189–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Furukawa, T., Lohith, T. G., Takamatsu, S., Mori, T., Tanaka, T., & Fujibayashi, Y. (2006). Potential of the FES-hERL PET reporter gene system – basic evaluation for gene therapy monitoring. Nuclear Medicine and Biology, 33(1), 145–51.

    CAS  PubMed  Google Scholar 

  100. Vandeputte, C., Evens, N., Toelen, J., Deroose, C. M., Bosier, B., Ibrahimi, A., et al. (2011). A PET brain reporter gene system based on type 2 cannabinoid receptors. Journal of Nuclear Medicine, 52(7), 1102–9.

    CAS  PubMed  Google Scholar 

  101. Dohan, O., De la Vieja, A., Paroder, V., Riedel, C., Artani, M., Reed, M., et al. (2003). The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocrine Reviews, 24(1), 48–77.

    CAS  PubMed  Google Scholar 

  102. Van Sande, J., Massart, C., Beauwens, R., Schoutens, A., Costagliola, S., Dumont, J. E., et al. (2003). Anion selectivity by the sodium iodide symporter. Endocrinology, 144(1), 247–52.

    PubMed  Google Scholar 

  103. Chung, J. K. (2002). Sodium iodide symporter: its role in nuclear medicine. Journal of Nuclear Medicine, 43(9), 1188–200.

    CAS  PubMed  Google Scholar 

  104. Mandell, R. B., Mandell, L. Z., & Link, C. J., Jr. (1999). Radioisotope concentrator gene therapy using the sodium/iodide symporter gene. Cancer Research, 59(3), 661–8.

    CAS  PubMed  Google Scholar 

  105. Shimura, H., Haraguchi, K., Miyazaki, A., Endo, T., & Onaya, T. (1997). Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I- symporter gene. Endocrinology, 138(10), 4493–6.

    CAS  PubMed  Google Scholar 

  106. Spitzweg, C., O’Connor, M. K., Bergert, E. R., Tindall, D. J., Young, C. Y., & Morris, J. C. (2000). Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Research, 60(22), 6526–30.

    CAS  PubMed  Google Scholar 

  107. Schipper, M. L., Weber, A., Behe, M., Goke, R., Joba, W., Schmidt, H., et al. (2003). Radioiodide treatment after sodium iodide symporter gene transfer is a highly effective therapy in neuroendocrine tumor cells. Cancer Research, 63(6), 1333–8.

    CAS  PubMed  Google Scholar 

  108. Faivre, J., Clerc, J., Gerolami, R., Herve, J., Longuet, M., Liu, B., et al. (2004). Long-term radioiodine retention and regression of liver cancer after sodium iodide symporter gene transfer in wistar rats. Cancer Research, 64(21), 8045–51.

    CAS  PubMed  Google Scholar 

  109. Terrovitis, J., Kwok, K. F., Lautamaki, R., Engles, J. M., Barth, A. S., Kizana, E., et al. (2008). Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography. Journal of the American College of Cardiology, 52(20), 1652–60.

    PubMed  Google Scholar 

  110. Quach, C. H., Jung, K. H., Paik, J. Y., Park, J. W., Lee, E. J., & Lee, K. H. (2012). Quantification of early adipose-derived stem cell survival: comparison between sodium iodide symporter and enhanced green fluorescence protein imaging. Nuclear Medicine and Biology, 39(8), 1251–60.

    CAS  PubMed  Google Scholar 

  111. Wolfs, E., Holvoet, B., Gijsbers, R., Casteels, C., Roberts, S. J., Struys, T., et al. (2014). Optimization of multimodal imaging of mesenchymal stem cells using the human sodium iodide symporter for PET and Cerenkov luminescence imaging. PloS One, 9(4), e94833.

    PubMed Central  PubMed  Google Scholar 

  112. Higuchi, T., Anton, M., Dumler, K., Seidl, S., Pelisek, J., Saraste, A., et al. (2009). Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart. Journal of Nuclear Medicine, 50(7), 1088–94.

    CAS  PubMed  Google Scholar 

  113. Dwyer, R. M., Ryan, J., Havelin, R. J., Morris, J. C., Miller, B. W., Liu, Z., et al. (2011). Mesenchymal stem cell-mediated delivery of the sodium iodide symporter supports radionuclide imaging and treatment of breast cancer. Stem Cells, 29(7), 1149–57.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Knoop, K., Kolokythas, M., Klutz, K., Willhauck, M. J., Wunderlich, N., Draganovici, D., et al. (2011). Image-guided, tumor stroma-targeted 131I therapy of hepatocellular cancer after systemic mesenchymal stem cell-mediated NIS gene delivery. Molecular Therapy, 19(9), 1704–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Templin, C., Zweigerdt, R., Schwanke, K., Olmer, R., Ghadri, J. R., Emmert, M. Y., et al. (2012). Transplantation and tracking of human-induced pluripotent stem cells in a pig model of myocardial infarction: assessment of cell survival, engraftment, and distribution by hybrid single photon emission computed tomography/computed tomography of sodium iodide symporter transgene expression. Circulation, 126(4), 430–9.

    CAS  PubMed  Google Scholar 

  116. Barton, K. N., Stricker, H., Brown, S. L., Elshaikh, M., Aref, I., Lu, M., et al. (2008). Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate. Molecular Therapy, 16(10), 1761–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Moroz, M. A., Serganova, I., Zanzonico, P., Ageyeva, L., Beresten, T., Dyomina, E., et al. (2007). Imaging hNET reporter gene expression with 124I-MIBG. Journal of Nuclear Medicine, 48(5), 827–36.

    CAS  PubMed  Google Scholar 

  118. Doubrovin, M. M., Doubrovina, E. S., Zanzonico, P., Sadelain, M., Larson, S. M., & O’Reilly, R. J. (2007). In vivo imaging and quantitation of adoptively transferred human antigen-specific T cells transduced to express a human norepinephrine transporter gene. Cancer Research, 67(24), 11959–69.

    CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

The authors declare no potential conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christophe M. Deroose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wolfs, E., Verfaillie, C.M., Van Laere, K. et al. Radiolabeling Strategies for Radionuclide Imaging of Stem Cells. Stem Cell Rev and Rep 11, 254–274 (2015). https://doi.org/10.1007/s12015-014-9575-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-014-9575-3

Keywords

Navigation