[^sup 89^Zr]Oxinate^sub 4^ for long-term in vivo cell tracking by positron emission tomography

• Published in: European journal of nuclear medicine and molecular imaging 2015-02, Vol.42 (2), p.278
• Main Authors: Charoenphun, Putthiporn, Meszaros, Levente K, Chuamsaamarkkee, Krisanat, Sharif-paghaleh, Ehsan, Ballinger, James R, Ferris, Trevor J, Went, Michael J, Mullen, Gregory E, D, Blower, Philip J
• Format: Article
• Language: English
• Subjects: Cell adhesion & migration; Leukocytes; Medical imaging; Tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-014-2945-x

^sup 111^In (typically as [^sup 111^In]oxinate^sub 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 ^sup 89^Zr PET tracer for cell labelling and compare it with [^sup 111^In]oxinate^sub 3^ single photon emission computed tomography (SPECT). [^sup 89^Zr]Oxinate^sub 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 [^sup 89^Zr]oxinate^sub 4^ or [^sup 111^In]oxinate^sub 3^ was monitored for up to 14 days. ^sup 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 ^sup 111^In labelling. Retention of ^sup 89^Zr in cells in vitro after 24 h was significantly better (range 71 to >90 %) than ^sup 111^In (43-52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with ^sup 111^In or ^sup 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 ^sup 111^In. In liver, spleen and bone marrow at least 92 % of ^sup 89^Zr remained associated with eGFP-positive cells after 7 days in vivo. [^sup 89^Zr]Oxinate^sub 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.