Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

Abstract

With the rapid development of anti-cancer cell-based therapies, such as adoptive T cell therapies using tumor-infiltrating T cells, T cell receptor transduced T cells, and chimeric antigen receptor T cells, there has been a growing interest in imaging technologies to non-invasively track transferred cells in vivo. Cell tracking using ex vivo cell labeling with positron emitting radioisotopes for positron emission tomography (PET) imaging has potential advantages over single-photon emitting radioisotopes. These advantages include intrinsically higher resolution, higher sensitivity, and higher signal-to-background ratios. Here, we review the current status of recently developed Zirconium-89 (89 Zr)-oxine ex vivo cell labeling with PET imaging focusing on its applications and future perspectives. Labeling of cells with 89 Zr-oxine is completed in a series of relatively simple steps, and its low radioactivity doses required for imaging does not interfere with the proliferation or function of the labeled immune cells. Preclinical studies have revealed that 89 Zr-oxine PET allows high-resolution in vivo tracking of labeled cells for 1-2 weeks after cell transfer both in mice and non-human primates. These results provide a strong rationale for the clinical translation of 89 Zr-oxine PET-based imaging of cell-based therapy.

Translational Development of a Zr-89-Labeled Inhibitor of Prostate-specific Membrane Antigen for PET Imaging in Prostate Cancer

“…This assumption is supported by a number of studies. Current publications show that Zr-89 is bound intracellularly after it has been able to penetrate the cell wall as a lipophilic complex [ 30 , 31 ]. Fung et al[ 32 ] observed differences in the clearance rates of radioactivity from the tumor for two forms of the humanized monoclonal antibody J591 ([ 124 I]I-J591 and [ 89 Zr]Zr-J591) against prostate-specific membrane antigen (PSMA) in mice with LNCaP tumors.…”

The Future of Cancer Diagnosis, Treatment and Surveillance: A Systemic Review on Immunotherapy and Immuno-PET Radiotracers

“…In 2003, Meidenbauer et al [ 49 ] labeled Melan-A-specific CD8 + cytotoxic T lymphocytes with [ 111 In]oxine and demonstrated the localization of these radiolabeled cells to metastatic sites 48 h after injection [ 49 ]. More recently, several groups [ 50 , 51 , 52 ] have studied ex-vivo CAR-T cells labeling techniques using [ 89 Zr] for PET imaging. The synthesis and labelling steps are similar to those used for the [ 111 In]oxine complex, but the use of [ 89 Zr] is more promising, owing to the higher spatial resolution, higher sensitivity, and better signal-to-background ratio of PET compared with SPECT, and owing to its comparably long half-life of 3.27 days compared to 2.80 days for 111In, which is helpful to monitor cell distribution in murine models after administration [ 53 ].…”

Toward comprehensive imaging of oncolytic viroimmunotherapy

“…Perhaps the most clinically advanced form of in vivo targeting and also adoptive cell radiolabeling is found in zirconium (89-Zr). 29 Notably more specific than other tracers such as 18-F given its independence from glucose metabolism, 30 89-Zr also has the advantages of a long half-life (3.3 days), making it helpful for tracking Molecular Therapy: Oncolytics Vol. 23 December 2021 cells during at least several days with serial CT-PET imaging.…”

“…23 December 2021 cells during at least several days with serial CT-PET imaging. 29 Moreover, its relatively lower positron energy fosters enhanced resolution of PET images. While other more specific tracers such as copper are also being studied, the half-life is comparatively short and the background signal is also prohibitive in some cases.…”