Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy (original) (raw)

Nature Biotechnology volume 23, pages 1407–1413 (2005)Cite this article

Abstract

The success of cellular therapies will depend in part on accurate delivery of cells to target organs. In dendritic cell therapy, in particular, delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. We show here that in vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information. Autologous dendritic cells were labeled with a clinical superparamagnetic iron oxide formulation or 111In-oxine and were co-injected intranodally in melanoma patients under ultrasound guidance. In contrast to scintigraphic imaging, magnetic resonance imaging (MRI) allowed assessment of the accuracy of dendritic cell delivery and of inter- and intra-nodal cell migration patterns. MRI cell tracking using iron oxides appears clinically safe and well suited to monitor cellular therapy in humans.

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Acknowledgements

Nicole Scharenborg, Mary-lène Brouwer, Annemiek de Boer, Mandy van de Rakt, Mariëlle Philippens, Giulio Gambarota, Andor Veltien, Simon Strijk, Sandra Croockewit, Jos Rijntjes, Emile Koenders, Peter Laverman and Hans Jacobs are acknowledged for their assistance. This work was supported by grants KUN 1999/1950 and 2004/3126 from the Dutch Cancer Society, grant 920-03-250 from the Netherlands Organization for Scientific Research, grants NGT.6719 and NGT.6721 of the Dutch Program for Tissue Engineering, the TIL-foundation, NOTK-foundation and NIH RO1 NS045062. The authors are grateful to Richard A.J. Janssen for his contribution in the initiation of this work.

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Authors and Affiliations

  1. Department of Tumor Immunology, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    I Jolanda M de Vries, Pauline Verdijk, Gosse J Adema & Carl G Figdor
  2. Department of Pediatric Oncology, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    I Jolanda M de Vries
  3. Department of Medical Oncology, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    W Joost Lesterhuis & Cornelis J A Punt
  4. Department of Radiology, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    Jelle O Barentsz, Tom W J Scheenen & Arend Heerschap
  5. Department of Pathology, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    J Han van Krieken
  6. Department of Nuclear Medicine, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    Otto C Boerman & Wim J G Oyen
  7. Department of Surgery, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    Johannes J Bonenkamp
  8. Central Hematological Laboratory, Radboud University Nijmegen Medical Center and Nijmegen Center for Molecular Life Sciences, Geert Grooteplein 28, Nijmegen, 6500 HB, The Netherlands
    Jan B Boezeman
  9. The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, and Institute for Cell Engineering, Johns Hopkins University School of Medicine, 217 Traylor, 720 Rutland Ave., Baltimore, 21205, Maryland, USA
    Jeff W M Bulte

Authors

  1. I Jolanda M de Vries
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  2. W Joost Lesterhuis
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  3. Jelle O Barentsz
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  4. Pauline Verdijk
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  5. J Han van Krieken
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  6. Otto C Boerman
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  7. Wim J G Oyen
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  8. Johannes J Bonenkamp
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  9. Jan B Boezeman
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  10. Gosse J Adema
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  11. Jeff W M Bulte
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  12. Tom W J Scheenen
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  13. Cornelis J A Punt
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  14. Arend Heerschap
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  15. Carl G Figdor
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Corresponding authors

Correspondence toJeff W M Bulte or Carl G Figdor.

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Supplementary information

Supplementary Fig. 1

Monitoring of in vivo migration of SPIO and 111In-labeled DCs with MR imaging and scintigraphy. (PDF 523 kb)

Supplementary Fig. 2

Number of LN positive for labeled DC imaged with MR and scintigraphy. (PDF 38 kb)

Supplementary Video 1

A movie of MR images showing the LN injected with SPIO-labeled DCs (injection site) and three surrounding LNs (migration sites). (MOV 931 kb)

Supplementary Video 2

MR images of sequential slices through a LN injected with SPIO-labeled cells and a draining LN. (MOV 885 kb)

Supplementary Video 3

MR images of sequential slices through a following LN beyond the injection node. (MOV 724 kb)

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de Vries, I., Lesterhuis, W., Barentsz, J. et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy.Nat Biotechnol 23, 1407–1413 (2005). https://doi.org/10.1038/nbt1154

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