[89Zr(oxinate)4] for cell tracking using PET

1239 Objectives For decades 111In-oxine has been used in nuclear medicine for labelling WBCs to diagnose infection/inflammation. Clinical PET provides greater resolution than SPECT hence may offer improved sensitivity to detect small lesions. A suitable PET tracer for cell labelling has long been sought. Cell labelling with 18F-FDG and 64Cu-PTSM are problematic due to short half life and rapid release from labelled cells. Long-lived PET isotopes offer the advantage to track labelled stem cells or immune cells for longer period. In this study a novel compound [89Zr(oxinate)4] was synthesised and evaluated in vitro and in vivo using PET imaging in eGFP-5T33 murine multiple myeloma model. 5T33 cells exclusively home in the spleen, liver and skeleton of C57Bl/KaLwRij mice. Methods eGFP-5T33 cells were labelled with [89Zr(oxinate)4] to determine labelling efficiency and rate of efflux. For in vivo studies cells were labelled with [89Zr(oxinate)4] and injected i.v. into C57Bl/KaLwRij mice (1MBq for ex vivo tissue counting (n=4), 2 MBq for FACS sorting (n=3) and 5 MBq for imaging (n=1). Mice were sacrificed 7 days post inoculation for ex vivo tissue counting. Liver, spleen and bone marrow homogenates were FACS sorted to confirm that radioactivity was associated with eGFP+ cells. One mouse was imaged for up to 14 days. Results Labelling yield of [89Zr(oxinate)4] with the cells was 32±1% and 71±1% was retained in cells 24 h after labelling. In vivo, [89Zr(oxinate)4] labelled cells accumulated mostly in liver, spleen and skeleton whereas uptake in other tissues and organs was low. These results were confirmed by PET. Activity in eGFP+ cell populations was ca.10-times higher than in eGFP- populations confirming that cells retained the tracer in vivo. Conclusions [89Zr(oxinate)4] was successfully used to track labelled cells in vivo for up to 14 days. FACS results proved that 89Zr was associated with the cells for at least 7 days in vivo. [89Zr(oxinate)4] is a promising PET tracer for cell tracking in vivo.