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

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Author(s): Yin Wu | Andreas Klaus Pfeifer | Rebecca Myschetzky | Rajendra Singh Garbyal | Palle Rasmussen | Ulrich Knigge | Michael Bzorek | Michael Holmsgaard Kristensen | Andreas Kjaer

Journal: Diagnostics
ISSN 2075-4418

Volume: 3;
Issue: 4;
Start page: 344;
Date: 2013;
Original page

Keywords: PRRT | 177Lu-DOTATATE | CD86+ | CD49b+ | FasL+ | dendritic cells | NK cells

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.
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