Examining Immunotherapy Response Using Multiple Radiotracers.

Purpose: Cancer immunotherapy has shown huge potential in the fight against cancer, but only a small proportion of patients respond successfully to treatment. Non-invasive methods to stratify responders from non-responders are critically important as immune therapies are often associated with immune-related side effects. Currently, conventional clinical imaging modalities do not provide a useful measure of immune therapy efficacy. Sensitive imaging biomarkers that provide information about the tumoural microenvironment may provide useful insights allowing for improved patient management.

Procedures: We have assessed the ability of a number of radiopharmaceuticals to non-invasively measure different aspects of the tumour microenvironment and correlated tumour uptake to immune therapy response in a syngeneic model of colon cancer, CT26-WT. Four radiopharmaceuticals, [F]FDG (a glucose analogue), [F]FEPPA (a marker for macrophage activation), [F]FB-IL2 (a marker for CD25 cells) and [Ga] Ga-mNOTA-GZP (a marker for granzyme B, the serine protease downstream effector of cytotoxic T cells), were assessed as potential biomarkers to help stratify response to PD-1 monotherapy or combined anti-PD1 and CLTA4 therapy in vivo correlating tumour uptake with changes in tumour-associated immune cell populations.

Results: [F]FDG, [F]FEPPA and [F]FB-IL2 (a marker for CD25 cells) showed limited ability to determine therapy response and showed little correlation to tumour-associated immune cell changes. However, [Ga] Ga-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8 T cells.

Conclusions: [Ga]Ga-mNOTA-GZP uptake correlates well with changes in CD8 T cell populations supporting continued development of granzyme B-based imaging agents for stratification of response to immunotherapy. Early assessment of immunotherapy efficacy with [Ga]Ga-mNOTA-GZP may allow for the reduction of unnecessary side effects while significantly improving patient management.