The other immuno-PET: Metabolic tracers in evaluation of immune responses to immune checkpoint inhibitor therapy for solid tumors

Abstract

Unique patterns of response to immune checkpoint inhibitor therapy, discernable in the earliest clinical trials, demanded a reconsideration of the standard methods of radiological treatment assessment. Immunomonitoring, that characterizes immune responses, offers several significant advantages over the tumor-centric approach currently used in the clinical practice: 1) better understanding of the drugs’ mechanism of action and treatment resistance, 2) earlier assessment of response to therapy, 3) patient/therapy selection, 4) evaluation of toxicity and 5) more accurate end-point in clinical trials. PET imaging in combination with the right agent offers non-invasive tracking of immune processes on a whole-body level and thus represents a method uniquely well-suited for immunomonitoring. Small molecule metabolic tracers, largely neglected in the immuno-PET discourse, offer a way to monitor immune responses by assessing cellular metabolism known to be intricately linked with immune cell function. In this review, we highlight the use of small molecule metabolic tracers in imaging immune responses, provide a view of their value in the clinic and discuss the importance of image analysis in the context of tracking a moving target.

The development process of ‘fit-for-purpose’ imaging biomarkers to characterize the tumor microenvironment

“…Many PET ligands ranging in size from 11 C-or 18 F-labeled small molecules to 89 Zr-labeled therapeutic antibodies targeting molecular features of the TME have been described (Figures 2, 3) (13,14,(25)(26)(27). They provide impressive insights into TME's enabling assessment of intralesional heterogeneity as well as of the tumor lesion heterogeneity within and between patients and its modulation caused by a pharmacological intervention (17,(28)(29)(30).…”

A feasibility study of [18F]F-AraG positron emission tomography (PET) for cardiac imaging – myocardial viability in ischemia-reperfusion injury model

“…[ 18 F]F-AraG was originally developed for imaging activated T cells [ 13 – 15 ]., and has been evaluated in a number of preclinical models including response to immune checkpoint inhibitor (ICI) therapy [ 16 ], acute graft-versus-host disease [ 17 ], immunomodulation and tumor profiling [ 18 ], arthritis [ 19 ] and multiple sclerosis [ 20 ]. [ 18 F]F-AraG was also investigated in healthy human subjects [ 21 , 22 ], cancer patients [ 23 ] and in COVID–19 convalescent subjects [ 24 ].…”