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Diagnostics 2013, 3(4), 344-355; doi:10.3390/diagnostics3040344
Article

Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

1,2,†,* , 2,†
, 2,3
, 4
, 5
, 2,6
, 4
, 4
 and 2,3
1 Peter Gorer Department of Immunobiology, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK 2 Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark 3 Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark 4 Department of Clinical Pathology, Næstved Hospital, Ringstedgade 61, Naestved, 4700, Denmark 5 Risø National Laboratory, Danish Technical University, Anker Engelunds Vej 1, Lyngby, 2100, Denmark 6 Department of Surgery C, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 26 August 2013 / Revised: 11 September 2013 / Accepted: 13 September 2013 / Published: 2 October 2013
(This article belongs to the collection Feature Papers)
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Abstract

Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.
Keywords: PRRT; 177Lu-DOTATATE; CD86+; CD49b+; FasL+; dendritic cells; NK cells PRRT; 177Lu-DOTATATE; CD86+; CD49b+; FasL+; dendritic cells; NK cells
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Wu, Y.; Pfeifer, A.K.; Myschetzky, R.; Garbyal, R.S.; Rasmussen, P.; Knigge, U.; Bzorek, M.; Kristensen, M.H.; Kjaer, A. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor. Diagnostics 2013, 3, 344-355.

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