In Vivo PET Tracking of 89Zr-Labeled V?9V?2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate.
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ABSTRACT: Gammadelta T (??-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion, and favorable safety profile. The development of ??-T cell therapies would benefit from non-invasive cell-tracking methods and increased targeting to tumor sites. Here we report the use of [89Zr]Zr(oxinate)4 to track V?9V?2 T cells in vivo by positron emission tomography (PET). In vitro, we showed that 89Zr-labeled V?9V?2 T cells retained their viability, proliferative capacity, and anti-cancer cytotoxicity with minimal DNA damage for amounts of 89Zr ?20 mBq/cell. Using a mouse xenograft model of human breast cancer, 89Zr-labeled ??-T cells were tracked by PET imaging over 1 week. To increase tumor antigen expression, the mice were pre-treated with PEGylated liposomal alendronate. Liposomal alendronate, but not placebo liposomes or non-liposomal alendronate, significantly increased the 89Zr signal in the tumors, suggesting increased homing of ??-T cells to the tumors. ??-T cell trafficking to tumors occurred within 48 hr of administration. The presence of ??-T cells in tumors, liver, and spleen was confirmed by histology. Our results demonstrate the suitability of [89Zr]Zr(oxinate)4 as a cell-labeling agent for therapeutic T cells and the potential benefits of liposomal bisphosphonate treatment before ??-T cell administration.
SUBMITTER: Man F
PROVIDER: S-EPMC6318719 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
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