Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging

An Effective Immuno-PET Imaging Method to Monitor CD8-Dependent Responses to Immunotherapy

“…Direct radiolabeling of lymphocytes ex vivo allows for monitoring initial cell migration of adoptively transferred cells, but suffers from radionuclide half-life, probe dilution due to cell division and potential toxic effects of the radionuclide on radiosensitive lymphocytes (33–35). Reporter gene transduction of cells ex vivo benefits from signal amplification due to cell division, repeat monitoring, and longitudinal tracking of genetically engineered cells (36–39). However, reporter probes demonstrate high background in clearance organs and reporter genes require development of non-immunogenic reporters for translation (37, 40).…”

Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors

“…Similarly, while the quantification of adoptively transferred cells in circulation provides useful information regarding their proliferation, researchers and clinicians are blind as to whether the dynamism in T cell numbers relates to expansion at the primary tumor site, metastatic foci, or at off-tumor sites (5). The ability to map the physical distribution and expansion of adoptively transferred T cells throughout the body in a longitudinal manner could therefore significantly improve real-time monitoring of T cell activity against tumors, potential toxicity from off-tumor-site targeting, and contribute to exploring adjuvant therapies to enhance adoptive T cell efficacy against solid cancers (5)(6)(7).…”

“…Current reporter genes used in preclinical and clinical studies are based on both intracellular enzymes, e.g., herpes simplex virus type-1 thymidine kinase (HSV1-tk) and human deoxycytidine kinase (14)(15)(16), and surface receptors, e.g., sodium iodide symporter (NIS) (17), prostate-specific membrane antigen (PSMA) (18), and SSTR2 (19). However, previous imaging studies have failed to demonstrate quantitative monitoring of critical T cell efficacy parameters, namely, whole-body, longitudinal visualization of T cell dynamics spanning initial localization, expansion, and subsequent contraction at primary and/or metastatic tumor sites, and the relationship between these parameters and tumor killing (5,13,(20)(21)(22). More importantly, imaging studies have yet to fully define treatment response parameters or prognostic markers of ACT efficacy and toxicity, and how these affect clinical outcomes in patients.…”

Immuno-PET Imaging of Engineered Human T Cells in Tumors

“…Promising novel approaches include the usage of reporter genes or antibody derivatives for imaging. Usage of reporter genes such as HSV1-tk has been closest to clinical translation with few patients treated, although technical and regulatory hurdles so far impede broader application (5,(11)(12)(13)(14)(15). In vivo imaging by Immuno-PET using antibody derivatives for targeting has been already clinically applied, although mainly for delineation of tumors (16).…”