New Developments in Imaging Cell-Based Therapy

Abstract

Cancer immunotherapy is now established as a central therapeutic pillar in hematologic oncology. Cell-based therapies, with or without genetic modification ex vivo, have reached the clinic as the standard of care in limited indications and remain the subject of intense preclinical and translational development. Expanding on this, related therapeutic approaches are in development for solid-tumor and nonmalignant indications, broadening the scope of this technology. It has long been recognized that in vivo tracking of infused cellular therapies would provide unique opportunities to optimize their efficacy and aid in the assessment and management of toxicity. Recently, we have witnessed the introduction of novel tracers for passive labeling of cell products and advances in the introduction and use of reporter genes to enable longitudinal imaging. This review highlights the key developments over the last 5 y.

Imaging of T-cells and their responses during anti-cancer immunotherapy

“…Reporter gene imaging strategies are characterised by ectopic expression of a transporters or enzymes, which is passed on to and maintained in filial generations upon cell division, thereby enabling the assessment of in vivo localisation and survival through molecular imaging [134] (Table 5 and Figure 2). Notably, reporter gene methodology does not require complex ex vivo cell labelling facilities and is less prone to associated cell damage/toxicities.…”

The Future of Nuclear Medicine, Molecular Imaging, and Theranostics

“…Another attractive approach for imaging the TME will be focused on small-molecule or peptide imaging agents. These can be used on their own, such as FAP inhibitors to target the tumor stroma (8); can be combined with reporter genes transfected into cellbased therapies (e.g., PSMA-targeting CAR-T cells), which can attack both tumor cells in prostate cancer but also the PMSA-expressing tumor neovasculature; or can be incorporated into pretargeted approaches (e.g., bispecific antibodies or bioorthogonal click chemistry) (9). Newly developed approaches, such as TME assessment with FAP inhibitor and immune modulation therapy assessment with in vivo T-cell labeling and with radiolabeled checkpoint inhibitors, will require Food and Drug Administration (FDA) approval, likely by a route different from the usual phase 1-2-3 scheme used for conventional drugs.…”

“…As a prerequisite for future successful clinical translation, properly designed prospective, randomized trials need to be conducted and published in leading medical journals (9). In addition, radiation dosimetry and genomic assessment of radiosensitivity will guide precision theranostics to avoid both undertreatment and off-target toxicity.…”

A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy

“…Not covered are the topics of imaging for ex vivo cellular therapies or imaging with quantum dots, nanoparticles, fluorescent dyes, contrast agents, or imaging of endogenously expressed proteins such as the dopamine D2 receptor (D2R), somatostatin receptor 2 (SSTR2), prostate-specific membrane antigen (PSMA), or transferrin receptor-1 (Tfr), but resources are provided for the reader’s interest. 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 Additionally, detailed reviews of imaging for OV and gene therapy are recommended. 27 , 28 , 29

Figure 1 Reporter gene imaging in oncolytic virotherapy and gene therapy Reporter genes are organized by imaging modality.

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