Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT:

Our goal was to validate the feasibility of 99mTc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of 99mTc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline. 99mTc-duramycin (37-55.5 MBq) was injected at 72 hours posttreatment, and single-photon emission computed tomography/computed tomography was performed at 2 hours postinjection. Apoptotic cells and activated caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular ultrastructural changes were assessed by light and transmission electron microscopy. 99mTc-duramycin with radiochemical purity of >90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-t...