Positron Emission Tomography Imaging of Functional Transforming Growth Factor β (TGFβ) Activity and Benefit of TGFβ Inhibition in Irradiated Intracranial Tumors

Purpose Transforming growth factor β (TGFβ) promotes cell survival by endorsing DNA damage repair and mediates an immunosuppressive tumor microenvironment. Thus, TGFβ activation in response to radiation therapy is potentially targetable because it opposes therapeutic control. Strategies assess this potential the clinic are needed. Methods Materials We evaluated positron emission tomography (PET) image 89Zr -fresolimumab, a humanized neutralizing monoclonal antibody, as means detect intracranial models. Pathway activity of was validated immunodetection phosphorylated SMAD2 target, tenascin. The contribution assessed Kaplan-Meier analysis mice bearing murine models GL261 SB28 glioblastoma brain-adapted 4T1 breast cancer (4T1-BrA) treated with 1D11, and/or focal (10 Gy). Results 89Zr-fresolimumab PET imaging detected engineered, physiological, radiation-induced activation, which confirmed immunostaining biological markers. tumors had greater signal compared similar-sized tumors, whereas widespread 4T1-BrA consistent their highly dispersed histologic distribution. Survival 1D11 antibody alone similar that control improved when given combination radiation. extent benefit associated degree PET. Conclusions This study demonstrates detects tumors. Functional indicated range but blockade provided only context treatment. provides further evidence