1. Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT.
- Author
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Luo R, Niu L, Qiu F, Fang W, Fu T, Zhao M, Zhang YJ, Hua ZC, Li XF, and Wang F
- Subjects
- Animals, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis, Bacteriocins pharmacokinetics, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Cell Line, Tumor, Feasibility Studies, Female, Humans, Mice, Organotechnetium Compounds pharmacokinetics, Paclitaxel pharmacology, Phosphatidylethanolamines metabolism, Radiopharmaceuticals pharmacokinetics, Random Allocation, Tomography, Emission-Computed, Single-Photon methods, Treatment Outcome, Xenograft Model Antitumor Assays, Antineoplastic Agents, Phytogenic administration & dosage, Bacteriocins administration & dosage, Breast Neoplasms diagnostic imaging, Organotechnetium Compounds administration & dosage, Paclitaxel administration & dosage, Radiopharmaceuticals administration & dosage
- Abstract
Our goal was to validate the feasibility of(99m)Tc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of(99m)Tc-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.(99m)Tc-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.(99m)Tc-duramycin with radiochemical purity of >90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of(99m)Tc-duramycin (ex vivo) significantly increased following paclitaxel treatment, which was consistent with apoptotic index, histological findings, and ultrastructural changes. Our data demonstrated the feasibility of(99m)Tc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts., (© The Author(s) 2016.)
- Published
- 2016
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