A new technique for the radiolabelling of mixed leukocytes with zirconium‐89 for inflammation imaging with positron emission tomography

Abstract

Mixed leukocyte (white blood cells [WBCs]) trafficking using positron emission tomography (PET) is receiving growing interest to diagnose and monitor inflammatory conditions. PET, a high sensitivity molecular imaging technique, allows precise quantification of the signal produced from radiolabelled moieties. We have evaluated a new method for radiolabelling WBCs with either zirconium‐89 (89Zr) or copper‐64 (64Cu) for PET imaging. Chitosan nanoparticles (CNs) were produced by a process of ionotropic gelation and used to deliver radiometals into WBCs. Experiments were carried out using mixed WBCs freshly isolated from whole human blood. WBCs radiolabelling efficiency was higher with [89Zr]‐loaded CN (76.8 ± 9.6% (n = 12)) than with [64Cu]‐loaded CN (26.3 ± 7.0 % (n = 7)). [89Zr]‐WBCs showed an initial loss of 28.4 ± 5.8% (n = 2) of the radioactivity after 2 h. This loss was then followed by a plateau as 89Zr remains stable in the cells. [64Cu]‐WBCs showed a loss of 85 ± 6% (n = 3) of the radioactivity after 1 h, which increased to 96 ± 6% (n = 3) loss after 3 h. WBC labelling with [89Zr]‐loaded CN showed a fast kinetic of leukocyte association, high labelling efficiency and a relatively good retention of the radioactivity. This method using 89Zr has a potential application for PET imaging of inflammation.

Cell Tracking in Cancer Immunotherapy

“…More recently 89 Zrlabeled CAR (Chimeric Antigen Receptor) T cells were shown to retain more than 60% of the 89 Zr over 6 days while their capacity of in vitro cytokine production, migration, and tumor cytotoxicity, as well as their in vivo antitumor activity (13) were preserved. To further reduce efflux rate and improve viability and cell functions, labeling mixed lymphocyte cell populations with Zr-89 radiolabeled nanoparticles was explored (14,15).…”

Radioactive polymeric nanoparticles for biomedical application

“…Polymeric nanoparticulate systems are reported as excellent diagnostic, therapeutic, and theranostic precursor agents. These systems are used for studies in numerous diseases such as ischemia, cardiovascular diseases (Hwang et al., 2014 ), angiogenesis (Almutairi et al., 2009 ), atherosclerosis (Delgado et al., 2000 ; Subramanian et al., 2010 ; Stendahl and Sinusas, 2015 ; Wang et al., 2017 ), inflammation, cancer (Delgado et al., 2000 ; Subramanian et al., 2010 ; Criscione et al., 2011 ; Liu et al., 2011 ; Wang et al., 2017 ), and infectious diseases (Delgado et al., 2000 ; Subramanian et al., 2010 ; Criscione et al., 2011 ; Liu et al., 2011 ; Seo et al., 2014 ; Aweda et al., 2015 ; Fairclough et al., 2016 ; Woodard et al., 2016 ; Dos Santos et al., 2017 ; Tu et al., 2018 ; Simonetti et al., 2019 ), among others. The radiolabeled NPs decorated or functionalized with amino acids, simple peptides, or dendrimers promote targeting to improve uptake, biocompatibility, and stability.…”

Multimodality Imaging in the Diagnostic Work-Up of Endocarditis and Cardiac Implantable Electronic Device (CIED) Infection

“…As for the radiopharmaceutical perspective, while radiolabeled granulocytes are a common clinical practice with SPECT applications, tracking WBC in vivo with PET using the positron emitting is still in the research phase [73][74][75]. A very interesting innovative strategy, based on the development of selective metabolic probes that are substrate for specific strains, has recently renewed the interest in pathogen-specific imaging agents.…”