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Biodistribution of radiolabelled human dendritic cells injected by various routes

  • Véronique QuillienEmail author
  • Annick Moisan
  • Andre Carsin
  • Thierry Lesimple
  • Claudia Lefeuvre
  • Henri Adamski
  • Nicolas Bertho
  • Anne Devillers
  • Claudine Leberre
  • Louis Toujas
Molecular Imaging

Abstract

Purpose

The purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol.

Methods

In the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with 111In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times).

Results

Scintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1–2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24 h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-α, IL-1β, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities.

Conclusion

The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection.

Keywords

Dendritic cells 111In-oxine Clinical trial Migration CC chemokine receptor 7 

Notes

Acknowledgements

We thank A. Gaudin, G. Duval, S. Abgrall and A. Trichet for their invaluable technical contribution. We are grateful to IDM company for its constant help and for provision of the VacCell Processor systems. The clinical protocol was carried out in conformity with the regulations in force in France, and, in particular, was accepted by the CCPPRB.

This trial was financed by a Hospital Clinical Research Programme (PHRC).

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Véronique Quillien
    • 1
    • 4
    Email author
  • Annick Moisan
    • 1
  • Andre Carsin
    • 1
  • Thierry Lesimple
    • 1
  • Claudia Lefeuvre
    • 1
  • Henri Adamski
    • 2
  • Nicolas Bertho
    • 1
  • Anne Devillers
    • 1
  • Claudine Leberre
    • 3
  • Louis Toujas
    • 1
  1. 1.Centre Régional de Lutte Contre le CancerRennesFrance
  2. 2.Service de dermatologieCHURennesFrance
  3. 3.Etablissement Français du Sang (EFS)RennesFrance
  4. 4.Unité de thérapie cellulaireCentre Eugène MarquisRennesFrance

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