Background
Advances in immunology and cell-based therapies are creating a need to track individual cell types, such as immune cells (neutrophils, eosinophils, chimeric antigen receptor (CAR) T cells, etc.) and stem cells. As the fate of administered cells remains largely unknown, nuclear imaging could determine the migration and survival of cells in patients. [89Zr]Zr(oxinate)4, or [89Zr]Zr-oxine, is a radiotracer for positron emission tomography (PET) that has been evaluated in preclinical models of cell tracking and could improve on [111In]In-oxine, the current gold standard radiotracer for cell tracking by scintigraphy and single-photon emission computed tomography (SPECT), because of the better sensitivity, spatial resolution and quantification of PET. However, a clinically usable formulation of [89Zr]Zr-oxine is lacking. This study demonstrates a 1-step procedure for preparing [89Zr]Zr-oxine and evaluates it against [111In]In-oxine in white blood cell (WBC) labelling.
Methods
Commercial [89Zr]Zr-oxalate was added to a formulation containing oxine, a buffering agent, a base and a surfactant or organic solvent. WBC isolated from 10 human volunteers were radiolabelled with [89Zr]Zr-oxine following a clinical radiolabelling protocol. Labelling efficiency, cell viability, chemotaxis and DNA damage were evaluated in vitro, in an intra-individual comparison against [111In]In-oxine.
Results
An optimised formulation of [89Zr]Zr-oxine containing oxine, polysorbate 80 and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) was developed. This enabled 1-step radiolabelling of oxine with commercial [89Zr]Zr-oxalate (0.1-25 MBq) in 5 min and radiotracer stability for 1 week. WBC labelling efficiency was 48.7 ± 6.3%, compared to 89.1 ± 9.5% (P < 0.0001, n = 10) for [111In]In-oxine. Intracellular retention of 89Zr and cell viability after radiolabelling were comparable to 111In. There were no significant differences in leukocyte chemotaxis or DNA damage between [89Zr]Zr-oxine or [111In]In-oxine. CONCLUSIONS, ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Our results demonstrate that [89Zr]Zr-oxine is a suitable PET alternative to [111In]In-oxine for WBC imaging. Our formulation allows rapid, stable, high-yield, single-step preparation of [89Zr]Zr-oxine from commercially available 89Zr. This will facilitate the clinical translation of cell tracking using [89Zr]Zr-oxine.