In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate

Gammadelta T (gamma delta-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion, and favorable safety profile. The development of gamma delta-T cell therapies would benefit from non-invasive celltracking methods and increased targeting to tumor sites. Here we report the use of [Zr-89] Zr(oxinate) 4 to track V gamma 9V delta 2 T cells in vivo by positron emission tomography (PET). In vitro, we showed that Zr-89-labeled V gamma 9V delta 2T cells retained their viability, proliferative capacity, and anti-cancer cytotoxicity with minimal DNA damage for amounts of Zr-89 <= 20 mBq/cell. Using a mouse xenograft model of human breast cancer, Zr-89-labeled gd-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 nonliposomal alendronate, significantly increased the Zr-89 signal in the tumors, suggesting increased homing of gamma delta-T cells to the tumors. gamma delta-T cell trafficking to tumors occurred within 48 hr of administration. The presence of gamma delta-T cells in tumors, liver, and spleen was confirmed by histology. Our results demonstrate the suitability of [Zr-89] Zr(oxinate) 4 as a cell-labeling agent for therapeutic T cells and the potential benefits of liposomal bisphosphonate treatment before gamma delta-T cell administration.