A kit formulation for the preparation of [89Zr]Zr(oxinate)4 for PET cell tracking: White blood cell labelling and comparison with [111In]In(oxinate)3

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Abstract

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.

Original languageEnglish
Pages (from-to)31-40
Number of pages10
JournalNuclear Medicine and Biology
Volume90-91
Early online date14 Sept 2020
DOIs
Publication statusPublished - 1 Nov 2020

Keywords

  • CAR-T
  • Cell therapy
  • Cell tracking
  • Nanomedicine
  • PET
  • Zirconium-89

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