imaging the immune tme

The goal of this project is to develop a robust diagnostic imaging tool for immunotherapy selection and assessment. Our goal is to directly measure the level of PD-L1 in tumors at baseline and in response to radiation using PET/MRI imaging.

Tumors expressing high levels of PD-L1 are susceptible to targeting with immunotherapy [9]. In contrast tumors with low expression of PD-L1 are resistant and can benefit from radiation as a mechanism for synergy with anti-PD-L1 as we previously demonstrated [7, 8]. Other groups have developed PET tracers based on labeled anti-PD-L1 antibodies that show high specificity in vitro but improvable in vivo results with only roughly 40% of the signal which is specific (60% cannot be blocked) [10]. A plausible reason for this discrepancy is the known link between inflammation and vascular permeability whose amplitude can vary from one tumor type to another. This means that accumulation of a targeted agent is attributed to both specific and non-specific uptake. As a confirmation for this mechanism, unspecific labeled antibodies are also detected in inflamed tumors. Therefore, it appears clearly that the specificity of PET tracer uptake must be measured along with the vascular permeability obtained from MRI.