Generation and use of long-lasting cell labeling agent for positron emission tomography (PET) imaging

Objectives Cell-based therapies, such as dendritic cell (DC) vaccines, immunotherapy, and stem cell transplants, have become increasingly important in the treatment of cancers. Development of non-invasive monitoring systems to track cells in a patient is critical for better understanding of the biology of these cells and to improve and optimize therapeutic strategies. Therefore, we developed a new cell labeling agent using a PET radiouclide emitter, Zirconium-89 (⁸⁹Zr).

Methods ⁸⁹Zr-oxine complex was synthesized and used for cell radiolabeling. Radiolabeling of cells with ⁸⁹Zr-oxine was tested using mouse bone marrow derived DCs, NK cells, and T cells; those cell types often used in cell-mediated therapies. Retention of radiolabel within the cells and survival of the cells after the labeling were examined. The labeled cells were transferred to C57BL/6 mice via a tail vein injection (148-370 kBq/5 million cells per mouse) and serial whole body images were acquired using a microPET imager up to 7 days post-injection.

Results Synthesis of ⁸⁹Zr-oxine complex from ⁸⁹Zr was accomplished in >97% yield. Sufficient cell labeling with ⁸⁹Zr-oxine for imaging was achieved within 15 min of incubation at room temperature in PBS. The labeling could be performed in serum free medium, if desired, when radiolabeling some types of cells sensitive to buffer conditions. Importantly, this labeling procedure did not negatively affect cell survival. ⁸⁹Zr incorporated into the cells was stable and enabled tracking of cells in mice for 7 days using a microPET imager. Compared to conventional ¹¹¹In-oxine, ⁸⁹Zr-oxine required only about 1/10 th of the radioactivity to acquire comparable images.

Conclusions We have developed a stable cell labeling agent for PET, ⁸⁹Zr-oxine, that enabled extended tracking of the cells with high sensitivity at a very low radioactive dose. This labeling method can be applied to various cell types used in clinical and basic research.