Research Article
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
Pierre-Simon Bellaye ,
1
Alexandra Oudot,
1
Jean-Marc Vrigneaud,
1
Olivier Raguin,
2
Francis Bichat,
2
Anne Vaslin,
3
H´ el` ene Maby-El Hajjami,
3
Claudio Zanna,
3
Gr´ egoire Vuagniaux,
3
Pierre Fumoleau,
1
Franck Denat,
4
François Brunotte,
1
and Bertrand Collin
1,4
1
Centre Georges-François Leclerc, Dijon, France
2
Oncodesign, Dijon, France
3
Debiopharm International SA, Lausanne, Switzerland
4
ICMUB, Dijon, France
Correspondence should be addressed to Pierre-Simon Bellaye; psbellaye@cgfl.fr
Received 13 July 2018; Accepted 18 October 2018; Published 2 December 2018
Academic Editor: Orazio Schillaci
Copyright © 2018 Pierre-Simon Bellaye et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
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. is 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. ese imaging biomarkers represent valuable noninvasive tools for translational and clinical research
in TNBC.
1. Background
e World Health Organization (WHO) reported that 1.7
million women were diagnosed with breast cancer in 2012
with a global number of 6.3 million women diagnosed with
breast cancer between 2008 and 2012 [1]. Since the last WHO
report in 2008, breast cancer incidence and mortality have
increased by more than 20% and 14%, respectively. Breast
cancer is also the leading cause of cancer-related death
among women (522,000 deaths in 2012) and the most fre-
quently diagnosed cancer in 140 of 184 countries worldwide
[1]. e combination of surgery, radiation therapy,
chemotherapy, and hormone therapy represents the com-
mon therapeutic strategies used nowadays in clinic to treat
breast cancer. Clinical and pathologic features (based on
conventional histology and immunohistochemistry) allow
breast cancer classification as hormone-receptor positive
(estrogen receptor (ER) and progesterone receptor (PR)),
HER2 (human epidermal growth factor receptor 2) positive,
and triple negative (ER, PR, and HER2 negative). is
classification process is currently necessary for prognosis
evaluation and individualized selection of therapy. Triple-
negative breast cancer (TNBC) is a heterogeneous disease
associated with a high risk of recurrence and poor prognosis.
Hindawi
Contrast Media & Molecular Imaging
Volume 2018, Article ID 8494031, 11 pages
https://doi.org/10.1155/2018/8494031