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

Purpose In-111 (typically as [In-111]oxinate(3)) 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 Zr-89 PET tracer for cell labelling and compare it with [In-111]oxinate(3) single photon emission computed tomography (SPECT). Methods [Zr-89]Oxinate(4) 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 [Zr-89]oxinate(4) or [In-111]oxinate3 was monitored for up to 14 days. Zr-89 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 In-111 labelling. Retention of Zr-89 in cells in vitro after 24 h was significantly better (range 71 to >90 %) than In-111 (43-52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with In-111 or Zr-89 (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for In-111. In liver, spleen and bone marrow at least 92 % of Zr-89 remained associated with eGFP-positive cells after 7 days in vivo. Conclusion [Zr-89]Oxinate(4) 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.