Whole-body immunoPET imaging to monitor immune activation status in situ

Abstract

Abstract Advances in immune modulation for cancer and inflammation warrant parallel development of imaging technologies to gauge in situ immune activity. We have developed a toolbox of full-length monoclonal antibody (mAb) positron emission tomography (immunoPET) tracers by desferrioxamine conjugation and 89Zr radiolabeling. Tracer uptake is reported as % injected dose/gram (%ID/g) tissue. Because mAbs to cell surface molecules often facilitate depletion, we tested enzymatic removal of the Fc glycan of CD8 mAb 2.43 to disrupt Fc:FcR interaction and prevent depletion. In the CT26 tumor model, CD8 immunoPET showed similar uptake between WT and deglycosylated tracers. However, unlike WT 2.43, the deglycosylated tracer did not deplete peripheral CD8 T cells, supporting this approach. In addition to surface markers, tracers that define cell function may have great utility. Checkpoint blockade therapy (anti-PD-1/anti-CTLA-4) in CT26-bearing mice shows IFNg immunoPET tracer uptake in 5/5 treated (16.5 ± 3.6 %ID/g) and 2/5 untreated (12.1 ± 4.8 %ID/g) tumors, possibly indicating baseline CT26 immunogenicity. To evaluate antigen presenting cell activation, an IL-12-specific tracer was also developed. Mouse mammary tumor TUBO-bearing mice showed enhanced tracer uptake after intratumoral injection of adenovirus encoding GM-CSF (2.6 ± 0.7 %ID/g) versus controls (0.4 ± 0.4 %ID/g). IL-12 PET was also tested for applications outside of cancer by mimicking inflammation with i.m. LPS injection. LPS-treated mice showed localized, elevated uptake at the site of injection (3.7 ± 0.7 %ID/g) versus controls (0.7 ± 0.1 %ID/g). These results support the use of immunoPET imaging for non-invasive monitoring of immune activity in situ. NIH R37 CA220482.