Positron Emission Tomography Reporter Genes and Reporter Probes: Gene and Cell Therapy Applications

Abstract

Positron emission tomography (PET) imaging reporter genes (IRGs) and PET reporter probes (PRPs) are amongst the most valuable tools for gene and cell therapy. PET IRGs/PRPs can be used to non-invasively monitor all aspects of the kinetics of therapeutic transgenes and cells in all types of living mammals. This technology is generalizable and can allow long-term kinetics monitoring. In gene therapy, PET IRGs/PRPs can be used for whole-body imaging of therapeutic transgene expression, monitoring variations in the magnitude of transgene expression over time. In cell or cellular gene therapy, PET IRGs/PRPs can be used for whole-body monitoring of therapeutic cell locations, quantity at all locations, survival and proliferation over time and also possibly changes in characteristics or function over time. In this review, we have classified PET IRGs/PRPs into two groups based on the source from which they were derived: human or non-human. This classification addresses the important concern of potential immunogenicity in humans, which is important for expansion of PET IRG imaging in clinical trials. We have then discussed the application of this technology in gene/cell therapy and described its use in these fields, including a summary of using PET IRGs/PRPs in gene and cell therapy clinical trials. This review concludes with a discussion of the future direction of PET IRGs/PRPs and recommends cell and gene therapists collaborate with molecular imaging experts early in their investigations to choose a PET IRG/PRP system suitable for progression into clinical trials.

Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors

“…However, as ACT has demonstrated both profound potency and at times, lethal toxicity, there is a clear need for tracking modalities that can provide additional spatiotemporal information to enable both baseline mapping of T cell localization and real-time visualization of multiple sites of T cell expansion. Quantitative PET imaging is increasingly used for diagnostic purposes and to gauge therapy response in a more accurate and objective manner (42). To our knowledge, this study is the first to utilize PET/CT to conduct highquality, longitudinal whole-body mapping of ACT localization that illustrates how its dynamics affect the course of treatment and survival outcomes.…”

Engineered antibody fragments for immuno-PET imaging of endogenous CD8 + T cells in vivo

“…However, this method has inherent limitations, such as radioisotope t 1/2 and cell division in vivo that lead to probe dilution. Reporter gene imaging, whereby cells are transfected with a PET reporter gene that encodes a protein specifically targeted via a radiolabeled reporter probe (7,8), has been used to image adoptive cell transfer of transduced T-cell receptor-engineered lymphocytes (9). Reporter gene imaging allows for longitudinal tracking of cells but relies on the ex vivo transfection of cells and, for clinical translation, the development of nonimmunogenic PET reporter proteins (8).…”

Noninvasive Molecular Imaging Using Reporter Genes

“…For example, HSV1-tk can be used as a therapeutic gene as well as a reporter gene. Although HSV1-tk has been used extensively in gene therapy clinical trials performed in the United States and Europe (42,43), only 3 clinical HSV1-tk gene imaging studies ( Fig. 1) (36-38) and 1 hNIS gene imaging study (40) have been reported.…”