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

Rui Luo, Lei Niu, Fan Qiu, Wei Fang, Tong Fu, Ming Zhao, Ying Jian Zhang, Zi Chun Hua, Xiao Feng Li, Feng Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of 99mTc-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 99mTc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts.

Original languageEnglish (US)
JournalMolecular Imaging
Volume15
DOIs
StatePublished - Jan 28 2016

Keywords

  • apoptosis
  • duramycin
  • neoadjuvant chemotherapy
  • phosphatidylethanolamine
  • tumor response monitoring

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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