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.

ABSTRACT:

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 ^99mTc-HYNIC-Annexin V, and a cell proliferation assay. ^99mTc-HYNIC-Annexin V SPECT and [¹⁸F]-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

SUBMITTER: Bellaye PS 

PROVIDER: S-EPMC6305031 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature