In vivo biodistribution and accumulation of 89Zr in mice

Abstract

Introduction The present investigation focuses on the chemical and biological fate of 89Zr in mice. Electrophoreses of 89Zr solvated or chelated in different conditions are here presented. The biological fate of mice injected with [89Zr]Zr-oxalate, [89Zr]Zr-chloride, [89Zr]Zr-phosphate, [89Zr]Zr-desferrioxamine and [89Zr]Zr-citrate is studied with the biodistribution, the clearances and PET images. A special focus is also given regarding the quality of 89Zr 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 [89Zr]Zr-chloride and [89Zr]Zr-oxalate reached 20% of ID after 6 days whereas [89Zr]Zr-phosphate was only 5% of ID. [89Zr]Zr-citrate and [89Zr]Zr-DFO were noticeably excreted after the first day p.i.. [89Zr]Zr-chloride and [89Zr]Zr-oxalate resulted in a respective bone uptake of ~15% ID/g and~20% ID/g at 8 h p.i. with minor losses after 6 days. [89Zr]Zr-citrate bone uptake was also observed, but [89Zr]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, 89Zr is a bone seeker and has a strong affinity for phosphate.

Immuno-PET Imaging of Engineered Human T Cells in Tumors

“…However, 89 Zr-labeling of an anti-HER2-Fab showed much better in vivo stability and tumor uptake compared with 124 I-labeling (45). There are a number of options for potential improvement as the usage of smaller constructs with rapid blood clearance (46), amino acid preloading (47), infusion of cold renal-blocking agents (48), introduction of metabolizable linkages facilitating excretion of radiometabolites (44), or infusion of DFO to capture free 89 Zr (49), which need to be evaluated in the future.…”

89Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T1‐Weighted MR Imaging

“…[ 32 ] Bone uptake (4.0 ± 0.7% ID/g) might indicate (partial) release of 89 Zr in circulation, as free 89 Zr is known to deposit in the mineralized constituents of the bone, where it is assumed to be chelated by phosphate constituents and epiphysis. [ 33,34 ] However, in humans injected with 89 Zr-DFO-labeled antibodies minimal 89 Zr bone-uptake is observed. [ 35 ] The faster metabolism of mice together with their less specifi c peptidases involving rapid degradation of 89 Zr-DFO are likely the root cause for the 89 Zr bone uptake in mice as observed in both this work as well as in studies with 89 Zr-DFOlabeled antibodies.…”

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

“…However, there would be an obligate reduction in radioactivity at proliferation sites where the cells migrate away. An additional limitation and a potential pitfall is that small amounts of 89 Zr will be released after cell death, resulting in accumulation of 89 Zr in the bone due to chelation by hydroxylapatite (36), in addition to clearance from the kidneys. However, this is a slow process that occurs as the labeled cells die as compared with live cells homing to the bone marrow.…”