[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography

PURPOSE: (111)In (typically as [(111)In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an (89)Zr PET tracer for cell labelling and compare it with [(111)In]oxinate3 single photon emission computed tomography (SPECT). METHODS: [(89)Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [(89)Zr]oxinate4 or [(111)In]oxinate3 was monitored for up to 14 days. (89)Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. RESULTS: Zr labelling was effective in all cell types with yields comparable with (111)In labelling. Retention of (89)Zr in cells in vitro after 24 h was significantly better (range 71 to >90%) than (111)In (43-52%). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with (111)In or (89)Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for (111)In. In liver, spleen and bone marrow at least 92% of (89)Zr remained associated with eGFP-positive cells after 7 days in vivo. CONCLUSION: [(89)Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types.