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

Figure 2

D1143 induces tumor apoptosis in vivo in a human breast adenocarcinoma murine model. (a) In vivo biodistribution of ^99mTc-HYNIC-Annexin V in tumor (MDA-MB-231 cells) bearing SCID mice (tumor in the right shoulder) 6 h and 24 h after receiving paclitaxel (iv), D1143 (po), or vehicle as control. Liver/spleen, kidneys, bladder, spine, and tumor activity are expressed as % ID/mm³. Results are presented as mean ± SEM; . (b) Representative SPECT pictures of ^99mTc-HYNIC-Annexin V in tumor (MDA-MB-231 cells) bearing SCID mice 6 h and 24 h after receiving paclitaxel (iv), D1143 (po), or vehicle as control. (c) Representative tumor-centered SPECT pictures of tumor (MDA-MB-231 cells) bearing SCID mice 6 h after receiving D1143 (po). (d) Specific ^99mTc-HYNIC-Annexin V tumor activity (% ID/mm³) of tumor- (MDA-MB-231 cells-) bearing SCID mice (tumor in the right shoulder) 6 h and 24 h after receiving paclitaxel (iv), D1143 (po), or vehicle as control. Results are presented as mean ± SEM; ; . (e) Gamma counting of ^99mTc-HYNIC-Annexin V in tumors in SCID mice 6h and 24h after receiving paclitaxel (iv), D1143 (po), or vehicle as control (%ID/g). Results are presented as mean ± SEM; and for the paclitaxel group 6 h, .