In vivo biodistribution and accumulation of 89Zr in mice

Introduction: The present investigation focuses on the chemical and biological fate of Zr-89 in mice. Electrophoreses of Zr-89 solvated or chelated in different conditions are here presented. The biological fate of mice injected with [Zr-89]Zr-oxalate, [Zr-89]Zr-chloride, [Zr-89]Zr-phosphate, [Zr-89]Zr-desferrioxamine and [Zr-89]Zr-citrate is studied with the biodistribution, the clearances and positron emission tomography images. A special focus is also given regarding the quality of Zr-89 bone accumulation. Methods: Electrophoreses were carried out on chromatography paper and read by gamma counting. Then, the solutions were intravenously injected in mice, imaged at different time points and sacrificed. The bones, the epiphysis and the marrow substance were separated and evaluated with gamma counts. Results: The clearances of [Zr-89]Zr-chloride and [Zr-89]Zr-oxalate reached 20% of injected dose (ID) after 6 days whereas [Zr-89]Zr-phosphate was only 5% of ID. [Zr-89-]Zr-citrate and [Zr-89]Zr-DFO were noticeably excreted after the first day postinjection (p.i.). [Zr-89]Zr-chloride and [Zr-89]Zr-oxalate resulted in a respective bone uptake of similar to 15% ID/g and similar to 20% ID/g at 8 h p.i. with minor losses after 6 days. [Zr-89]Zr-citrate bone uptake was also observed, but [Zr-89]Zr-phosphate was absorbed in high amounts in the liver and the spleen. The marrow cells were insignificantly radioactive in comparison to the calcified tissues. Conclusion: Despite the complexity of Zr coordination, the electrophoretic analyses provided detailed evidences of Zr charges either as salts or as complexes. This study also shows that weakly chelated, Zr-89 is a bone seeker and has a strong affinity for phosphate. (C) 2011 Elsevier Inc. All rights reserved.