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Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy

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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Figure 1: Study protocol.
Figure 2: Phenotypical and functional characterization of SPIO-labeled dendritic cells.
Figure 3: In vivo scintigraphic and MRI.
Figure 4: Monitoring of the accuracy of delivery of SPIO-labeled cells using MRI.
Figure 5: Ex vivo magnetic resonance images and correlation with histology.

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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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Correspondence to Jeff 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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