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

Purpose 111In (typically as [111In]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 89Zr PET tracer for cell

labelling and compare it with [111In]oxinate3 single photon

emission computed tomography (SPECT).

Methods [89Zr]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 [89Zr]oxinate4 or [111In]oxinate3

was monitored for up to 14 days. 89Zr 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 111In labelling. Retention of 89Zr in cells

in vitro after 24 h was significantly better (range 71 to

>90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo

showed the same early biodistribution whether labelled with

111In or 89Zr (initial pulmonary accumulation followed by

migration to liver, spleen and bone marrow), but later translocation

of radioactivity to kidneys was much greater for 111In.

In liver, spleen and bone marrow at least 92 % of 89Zr

remained associated with eGFP-positive cells after 7 days

in vivo.

Conclusion [89Zr]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.