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Published in: European Journal of Nuclear Medicine and Molecular Imaging 2/2015

Open Access 01-02-2015 | Original Article

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

Authors: Putthiporn Charoenphun, Levente K. Meszaros, Krisanat Chuamsaamarkkee, Ehsan Sharif-Paghaleh, James R. Ballinger, Trevor J. Ferris, Michael J. Went, Gregory E. D. Mullen, Philip J. Blower

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2015

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Abstract

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.
Appendix
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Metadata
Title
[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography
Authors
Putthiporn Charoenphun
Levente K. Meszaros
Krisanat Chuamsaamarkkee
Ehsan Sharif-Paghaleh
James R. Ballinger
Trevor J. Ferris
Michael J. Went
Gregory E. D. Mullen
Philip J. Blower
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2015
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2945-x

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