In Vivo PET Tracking of ⁸⁹Zr-Labeled V?9V?2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate.

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