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Published in: European Journal of Nuclear Medicine and Molecular Imaging 7/2005

01-07-2005 | Molecular Imaging

Biodistribution of radiolabelled human dendritic cells injected by various routes

Authors: Véronique Quillien, Annick Moisan, Andre Carsin, Thierry Lesimple, Claudia Lefeuvre, Henri Adamski, Nicolas Bertho, Anne Devillers, Claudine Leberre, Louis Toujas

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2005

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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.
Literature
1.
go back to reference Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J Clin Oncol 2003;21:2415–32 Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J Clin Oncol 2003;21:2415–32
2.
go back to reference Figdor CG, De Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med 2004;10:475–80CrossRefPubMed Figdor CG, De Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med 2004;10:475–80CrossRefPubMed
3.
go back to reference Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001;193:233–8CrossRefPubMed Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001;193:233–8CrossRefPubMed
4.
go back to reference Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000;192:1213–22CrossRefPubMed Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000;192:1213–22CrossRefPubMed
5.
go back to reference Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P. Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J Immunol 2000;164:4507–12PubMed Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P. Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J Immunol 2000;164:4507–12PubMed
6.
go back to reference Sallusto F, Palermo B, Lenig D, Miettinen M, Matikainen S, Julkunen I, et al. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol 1999;29:1617–25CrossRefPubMed Sallusto F, Palermo B, Lenig D, Miettinen M, Matikainen S, Julkunen I, et al. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol 1999;29:1617–25CrossRefPubMed
7.
go back to reference Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, et al. A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 2001;93:243–51CrossRefPubMed Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, et al. A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 2001;93:243–51CrossRefPubMed
8.
go back to reference Gilliet M, Kleinhans M, Lantelme E, Schadendorf D, Burg G, Nestle FO. Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen. Blood 2003;102:36–42.CrossRef Gilliet M, Kleinhans M, Lantelme E, Schadendorf D, Burg G, Nestle FO. Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen. Blood 2003;102:36–42.CrossRef
9.
go back to reference Bedrosian I, Mick R, Xu S, Nisenbaum H, Faries M, Zhang P, et al. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol 2003;21:3826–35 Bedrosian I, Mick R, Xu S, Nisenbaum H, Faries M, Zhang P, et al. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol 2003;21:3826–35
10.
go back to reference Lesimple T, Moisan A, Carsin A, Ollivier I, Mousseau M, Meunier B, et al. Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects. Cancer Immunol Immunother 2003;52:438–44CrossRefPubMed Lesimple T, Moisan A, Carsin A, Ollivier I, Mousseau M, Meunier B, et al. Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects. Cancer Immunol Immunother 2003;52:438–44CrossRefPubMed
11.
go back to reference Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, et al. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 2002;195:1279–88PubMed Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, et al. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 2002;195:1279–88PubMed
12.
go back to reference Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 1997;159:28–35PubMed Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 1997;159:28–35PubMed
13.
go back to reference Goxe B, Latour N, Chokri M, Abastado JP, Salcedo M. Simplified method to generate large quantities of dendritic cells suitable for clinical applications. Immunol Invest 2000;29:319–36PubMed Goxe B, Latour N, Chokri M, Abastado JP, Salcedo M. Simplified method to generate large quantities of dendritic cells suitable for clinical applications. Immunol Invest 2000;29:319–36PubMed
14.
go back to reference Boccaccio C, Jacod S, Kaiser A, Boyer A, Abastado JP, Nardin A. Identification of a clinical-grade maturation factor for dendritic cells. J Immunother 2002;25:88–96CrossRefPubMed Boccaccio C, Jacod S, Kaiser A, Boyer A, Abastado JP, Nardin A. Identification of a clinical-grade maturation factor for dendritic cells. J Immunother 2002;25:88–96CrossRefPubMed
15.
go back to reference Blocklet D, Toungouz M, Kiss R, Lambermont M, Velu T, Duriau D, et al. 111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content. Eur J Nucl Med Mol Imaging 2003;30:440–7PubMed Blocklet D, Toungouz M, Kiss R, Lambermont M, Velu T, Duriau D, et al. 111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content. Eur J Nucl Med Mol Imaging 2003;30:440–7PubMed
16.
go back to reference Thomas R, Chambers M, Boytar R, Barker K, Cavanagh LL, MacFadyen S, et al. Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy. Melanoma Res 1999;9:474–81PubMed Thomas R, Chambers M, Boytar R, Barker K, Cavanagh LL, MacFadyen S, et al. Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy. Melanoma Res 1999;9:474–81PubMed
17.
go back to reference Fong L, Brockstedt D, Benike C, Wu L, Engleman EG. Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 2001;166:4254–9PubMed Fong L, Brockstedt D, Benike C, Wu L, Engleman EG. Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 2001;166:4254–9PubMed
18.
go back to reference De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, et al. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 2003;63:12–7PubMed De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, et al. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 2003;63:12–7PubMed
19.
go back to reference Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998;4:328–32PubMed Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998;4:328–32PubMed
20.
go back to reference Eggert AA, Schreurs MW, Boerman OC, Oyen WJ, de Boer AJ, Punt CJ, et al. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 1999;59:3340–5PubMed Eggert AA, Schreurs MW, Boerman OC, Oyen WJ, de Boer AJ, Punt CJ, et al. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 1999;59:3340–5PubMed
21.
go back to reference Barratt-Boyes SM, Zimmer MI, Harshyne LA, Meyer EM, Watkins SC, Capuano S III, et al. Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol 2000;164:2487–95PubMed Barratt-Boyes SM, Zimmer MI, Harshyne LA, Meyer EM, Watkins SC, Capuano S III, et al. Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol 2000;164:2487–95PubMed
22.
go back to reference Morse MA, Coleman RE, Akabani G, Niehaus N, Coleman D, Lyerly HK. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res 1999;59:56–8PubMed Morse MA, Coleman RE, Akabani G, Niehaus N, Coleman D, Lyerly HK. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res 1999;59:56–8PubMed
23.
go back to reference Nair S, McLaughlin C, Weizer A, Su Z, Boczkowski D, Dannull J, et al. Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation. J Immunol 2003;171:6275–82PubMed Nair S, McLaughlin C, Weizer A, Su Z, Boczkowski D, Dannull J, et al. Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation. J Immunol 2003;171:6275–82PubMed
24.
go back to reference Scandella E, Men Y, Gillessen S, Forster R, Groettrup M. Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 2002;100:1354–61CrossRefPubMed Scandella E, Men Y, Gillessen S, Forster R, Groettrup M. Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 2002;100:1354–61CrossRefPubMed
25.
go back to reference Luft T, Jefford M, Luetjens P, Toy T, Hochrein H, Masterman KA, et al. Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E(2) regulates the migratory capacity of specific DC subsets. Blood 2002;100:1362–72CrossRefPubMed Luft T, Jefford M, Luetjens P, Toy T, Hochrein H, Masterman KA, et al. Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E(2) regulates the migratory capacity of specific DC subsets. Blood 2002;100:1362–72CrossRefPubMed
26.
go back to reference Kalinski P, Schuitemaker JH, Hilkens CM, Kapsenberg ML. Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: the levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol 1998;161:2804–9PubMed Kalinski P, Schuitemaker JH, Hilkens CM, Kapsenberg ML. Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: the levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol 1998;161:2804–9PubMed
27.
go back to reference Scandella E, Men Y, Legler DF, Gillessen S, Prikler L, Ludewig B, et al. CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2. Blood 2004;103:1595–601CrossRefPubMed Scandella E, Men Y, Legler DF, Gillessen S, Prikler L, Ludewig B, et al. CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2. Blood 2004;103:1595–601CrossRefPubMed
28.
go back to reference MartIn-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, et al. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 2003;198:615–21CrossRefPubMed MartIn-Fontecha A, Sebastiani S, Hopken UE, Uguccioni M, Lipp M, Lanzavecchia A, et al. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 2003;198:615–21CrossRefPubMed
29.
go back to reference Mullins DW, Sheasley SL, Ream RM, Bullock TN, Fu YX, Engelhard VH. Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control. J Exp Med 2003;198:1023–34PubMed Mullins DW, Sheasley SL, Ream RM, Bullock TN, Fu YX, Engelhard VH. Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control. J Exp Med 2003;198:1023–34PubMed
Metadata
Title
Biodistribution of radiolabelled human dendritic cells injected by various routes
Authors
Véronique Quillien
Annick Moisan
Andre Carsin
Thierry Lesimple
Claudia Lefeuvre
Henri Adamski
Nicolas Bertho
Anne Devillers
Claudine Leberre
Louis Toujas
Publication date
01-07-2005
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2005
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-005-1825-9

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