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Background   Debio 1143, a potent orally available SMAC mimetic, targets inhibitors of apoptosis proteins (IAPs) members and is currently in clinical trials. In this study, nuclear imaging evaluated the effects of Debio 1143 on tumor cell death and metabolism in a triple-negative breast cancer (TNBC) cell line (MDA-MB-231)-based animal model.Methods   Apoptosis induced by Debio 1143 was assessed by FACS (caspase-3, annexin 5 (A5)), binding of  99m Tc-HYNIC-Annexin V, and a cell proliferation assay.  99m Tc-HYNIC-Annexin V SPECT and [ 18 F]-FDG PET were also performed in mice xenografted with MDA-MB-231 cells.Results   Debio 1143 induced early apoptosis both  in vitro  and  in vivo  6 h after treatment. Debio 1143 inhibited tumor growth, which was associated with a decreased tumor [ 18 F]-FDG uptake when measured during treatment.Conclusions   This imaging study combining SPECT and PET showed the early proapoptotic effects of Debio 1143 resulting in a robust antitumor activity in a preclinical TNBC model. These imaging biomarkers represent valuable noninvasive tools for translational and clinical research in TNBC.

contrast media and molecular imaging/contrast media and molecular imaging

Nuclear Imaging Study of the Pharmacodynamic Effects of Debio 1143, an Antagonist of Multiple Inhibitor of Apoptosis Proteins (IAPs), in a Triple-Negative Breast Cancer Model