title: Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT.
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.
authors.affiliation: Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Niu
authors.affiliation: Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Cardiovascular Institute & Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Fu
authors.affiliation: Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Ying-Jian
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
authors.affiliation: Department of Radiology, University of Louisville, Louisville, KY, USA.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China fengwangcn@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D001430:Bacteriocins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D051379:Mice; D015609:Organotechnetium Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001430:Bacteriocins; D015609:Organotechnetium Compounds; D010714:Phosphatidylethanolamines; D019275:Radiopharmaceuticals; C578182:technetium 99m HYNIC-duramycin; C483858:phosphatidylethanolamine; D017239:Paclitaxel
keywords: apoptosis; duramycin; neoadjuvant chemotherapy; phosphatidylethanolamine; tumor response monitoring