Use of [11C]PBR28 to localize and quantify tumor associated macrophages in pancreas cancer (TUM6P.1008)

Abstract

Abstract Tumor associated macrophages (TAM) are an important part of the immune microenvironment in pancreas cancer (PC) and are associated with poor prognosis. We investigated the use of a novel radiolabeled small molecule ([11C]PBR28), which binds to the macrophage translocator protein (TSPO), to track TAMs in-vivo. A murine PC line was generated from a KRAS/P53 mutant transgenic mouse. Immunoblotting confirmed lack of endogenous TSPO expression. After subcutaneous implantation, mice were administered [11C]PBR28. After micro-PET imaging, organs and tumors were harvested for autoradiography. Immunoflourescent co-staining of tumors confirmed TAM infiltration with co-expression of F4/80 and TSPO. Following [11C]PBR28 injection, micro-PET successfully localized tumors and autoradiography demonstrated a 3-fold increase in tumor radioactivity compared to background (muscle). To confirm the observed activity was TAM specific, the experiment was repeated in CD11b+ diphtheria toxin receptor (DTR) transgenic mice. After tumor inoculation, diphtheria toxin (DT) was administered and macrophage depletion confirmed by immunofluorescence and flow cytometry. Autoradiography demonstrated equal tumor uptake relative to background and decreased levels compared to tumors from wild-type mice. We demonstrated a non-invasive method to quantify pancreatic cancer TAM infiltration in-vivo using a novel radiotracer. This could be used prognostically and to determine response to TAM based immunotherapy.