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

Abstract

Purpose:To develop a clinically translatable method of cell labeling with zirconium 89 ( 89 Zr) and oxine to track cells with positron emission tomography (PET) in mouse models of cell-based therapy. Materials andMethods:This study was approved by the institutional animal care committee. 89Zr-oxine complex was synthesized in an aqueous solution. Cell labeling conditions were optimized by using EL4 mouse lymphoma cells, and labeling efficiency was examined by using dendritic cells (DCs) (n = 4), naïve (n = 3) and activated (n = 3) cytotoxic T cells (CTLs), and natural killer (NK) (n = 4), bone marrow (n = 4), and EL4 (n = 4) cells. The effect of ] cells, n = 4) and by measuring the tumor size (n = 6). Two-way analysis of variance was used to compare labeling conditions, the Wilcoxon test was used to assess cell survival and proliferation, and Holm-Sidak multiple tests were used to assess tumor growth and perform biodistribution analyses. Results:89 Zr-oxine complex was synthesized at a mean yield of 97.3% 6 2.8 (standard deviation). It readily labeled cells at room temperature or 4°C in phosphate-buffered saline (labeling efficiency range, 13.0%-43.9%) and was stably retained (83.5% 6 1.8 retention on day 5 in DCs). Labeling did not affect the viability of DCs and CTLs when compared with nonlabeled control mice (P . .05), nor did it affect functionality. 89Zr-oxine complex enabled extended cell tracking for 7 days. Labeled tumor-specific CTLs accumulated in the tumor (4.6% on day 7) and induced tumor regression (P , .05 on day 7). Conclusion:We have developed a 89Zr-oxine complex cell tracking technique for use with PET that is applicable to a broad range of cell types and could be a valuable tool with which to evaluate various cell-based therapies.q RSNA, 2015

Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model

“…Ideally, a PET cell labeling agent should readily permeate the plasma membrane and be stably retained inside the cell for a period of days, while also causing limited cytotoxicity. 89 Zr-oxine complex is a novel agent that has been developed to meet these requirements based on the 3-day half-life of 89 Zr and the minimal amounts of radioactivity needed for imaging (11). …”

“…89 Zr-oxine complex was synthesized from 89 ZrCl 4 and oxine following the method previously reported (11). Briefly, 4 μl of 20% tween 80 solution (Sigma-Aldrich) and 102 μl of 20 mM oxine in 0.04 N HCl were mixed in a tube, and then, 60 μl of 89 ZrCl 4 (37 to 74 kBq) was added and vortexed.…”

“…We have previously reported development of a cell labeling agent, zirconium-89 ( 89 Zr)-oxine complex, for tracking cells with positron emission tomography (PET) imaging (11). To better understand the trafficking of HSCs in transplantation and mobilization in vivo , we applied this 89 Zr-oxine cell tracking method and employed microPET/computed tomography (CT) imaging in a mouse bone marrow (BM) transplant model.…”

19F-MRI for monitoring human NK cellsin vivo

“…Longer lived PET isotopes such as 89 Zr have recently been used in combination with more specific cell labeling strategies such as so-called "click chemistry" to enhance signal half-life and specificity with promising results. [46][47][48] However, prolonged exposure to ionizing radiation remains problematic for cell-trafficking approaches in the clinic. Perfluorcarbon…”

Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET

“…Previous methods of cell tracking employ an in vitro cell labeling step that can modify the function of cells when tracked by imaging. [7] …”