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[(89)Zr]oxinate4 for long-term in vivo cell tracking by positron emission tomography

Significance Statement

Tracking the migration of a patients’ own leukocytes by labeling them with gamma-emitting radionuclides (mainly 111In and 99mTc) and imaging with a gamma camera has been a routine method for detecting sites of infection and inflammation for many years. Recently, the need for tracking cells in humans in animals has expanded greatly because of new insight in immunological aspects of diseases such as cancer, atherosclerosis, stroke, transplant and asthma, creating interest in imaging the migration of individual immune cell types such as eosinophils , neutrophils, T-lymphocytes, and dendritic cells. Moreover, the growth of regenerative medicine and cell-based therapies creates a need to track stem cells and chimeric antigen receptor-expressing T-lymphocytes in clinical trials. For these clinical uses positron emission tomography (PET) will be better than gamma camera imaging  because it offers better sensitivity, quantification and resolution. Now that PET is becoming more widely available, there is a need for easy and reliable ways to label living cells with long half-life positron emitting radioisotopes capable of tracking cells in humans for 7 days or more. So far, the search for positron-emitting radiolabels for cells has met with limited success. Zirconium-89 (89Zr) is a long half-life positron emitter that could meet this need. This paper describes a simple and general method for labelling various several cell lines, in which the cells survive and retain their radioactivity in vivo for several days. Using the method, the homing of myeloma cells from intravenous injection to initial accumulation in the lungs, and then migration to liver, spleen and bone marrow was imaged in mice for up to 14 days.


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










Journal Reference

P. Charoenphun1,L. K. Meszaros1,K. Chuamsaamarkkee1,E. Sharif-Paghaleh 1,J. R. Ballinger 1,T. Ferris 2,MJ. Went2,G. E. D. Mullen1,P. J. Blower1,3 . Eur J Nucl Med Mol Imaging. 2015 Feb;42(2):278-87.

Show Affiliations

1. King’s College London, Division of Imaging Sciences and Biomedical Engineering, 4th Floor Lambeth Wing, St Thomas’ Hospital, London, SE1 7EH, UK.

2. School of Physical Sciences, University of Kent, Canterbury, CT2 7NH, UK

3. Division of Chemistry, King’s College London, Britannia House, 7 Trinity St, London, SE11DB, UK.



(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).


[(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.


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.


[(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.

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