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

Abstract

Purpose111In (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.ResultsZr 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-014-2945-x) contains supplementary material, which is available to authorized users.

89Zr-Oxine Complex PET Cell Imaging in Monitoring Cell-based Therapies

“…Zr-oxine complex was accomplished in an aqueous solution with simple steps of mixing, which resulted in more than 97% of 89 Zr being converted to the complex, allowing us to add the resulting solution to the cell suspension for labeling without further purification. Synthesis performed in an aqueous solution has substantial advantages over synthesis methods that use an organic solvent and require time-consuming procedures to evaporate the solvent and collect the lipophilic product with another solvent, as was recently reported (33). Our method eliminated the long preparation time and equipment required for these procedures.…”

Exploiting the Metal-Chelating Properties of the Drug Cargo for In Vivo Positron Emission Tomography Imaging of Liposomal Nanomedicines

“…8HQ, however, is extensively used in radiopharmacies for labeling cells with γ-emitting isotopes and hence does not represent a significant barrier for clinical translation 30 and has been recently been used for labeling cells with 89 Zr. 31 2HQ has been previously used to radiolabel with 64 Cu liposomes loaded with the chelator DOTA, 14 while here we report the use of 8HQ with the PET tracers 89 Zr and 52 Mn.…”

A new technique for the radiolabelling of mixed leukocytes with zirconium‐89 for inflammation imaging with positron emission tomography

“…[ 89 Zr]‐DFO‐NCS has however been used to randomly radiolabel primary amine groups at the surface of stem cells for PET‐based cell trafficking . More recently, [ 89 Zr]‐oxinate 4 has been used for in vivo cell trafficking with PET . This technique showed a radiolabelling yield comparable with that with indium‐111 SPECT, as well as a high retention of 89 Zr in cells; however, further evaluation of its potential cytotoxicity effects is required …”