Develop a PET radiotracer suitable for in vivo imaging of TGFβ

Project Summary/Abstract Transcription growth factor beta (TGFβ) is a pleiotropic cytokine with a significant role in creating an immunosuppressive tumor microenvironment. High levels of TGFβ are strongly associated with poor cancer prognosis, but there are currently no non-invasive methods available to quantify the cytokine in vivo. This

proposal describes the design and evaluation of a novel biologic positron emission tomography (PET) radiotracer to selectively and quantitatively detect TGFβ in vivo. The proposed biologic construct is a recombinant protein incorporating the extracellular domain of human TGFβ receptor II (TβRII) linked to the Fc fragment of human

IgG2 via the antibody hinge region. This recombinant protein was further modified by appending 1,4,7- triazacyclononane-1,4,7-triacetic acid (NOTA) copper chelator via a p-SCN-Bn reactive moiety. The resulting precursor molecule will be labeled with 64Cu to produce the active radiotracer, 64Cu-Fc:TβRII. The 64Cu-Fc:TβRII

radiotracer will be evaluated for preclinical efficacy by imaging mice using small animal PET-MRI. This proposal aims to assess the efficacy of 64Cu-Fc:TβRII including a dose titration experiment to determine the optimal dosage and incubation time for the radiotracer, a blocking study, a comparison of in vivo PET standardized

uptake values (SUVs) with ex vivo tumor lysate TGFβ concentrations in four murine tumor models, and an experiment to detect changes in TGFβ expression before and after radiation therapy.