title: Longitudinal PET imaging of doxorubicin-induced cell death with 18F-Annexin V.
abstract: OBJECTIVE
  This study aims to apply longitudinal positron emission tomography (PET) imaging with (18)F-Annexin V to visualize and evaluate cell death induced by doxorubicin in a human head and neck squamous cell cancer UM-SCC-22B tumor xenograft model.
  
  
  METHODS
  In vitro toxicity of doxorubicin to UM-SCC-22B cells was determined by a colorimetric assay. Recombinant human Annexin V protein was expressed and purified. The protein was labeled with fluorescein isothiocyanate for fluorescence staining and (18)F for PET imaging. Established UM-SCC-22B tumors in nude mice were treated with two doses of doxorubicin (10 mg/kg each dose) with 1 day interval. Longitudinal (18)F-Annexin V PET was performed at 6 h, 24 h, 3 days, and 7 days after the treatment started. Following PET imaging, direct tissue biodistribution study was performed to confirm the accuracy of PET quantification.
  
  
  RESULTS
  Two doses of doxorubicin effectively inhibited the growth of UM-SCC-22B tumors by inducing cell death including apoptosis. The cell death was clearly visualized by (18)F-Annexin V PET. The peak tumor uptake, which was observed at day 3 after treatment started, was significantly higher than that in the untreated tumors (1.56 ± 0.23 vs. 0.89 ± 0.31%ID/g, p < 0.05). Moreover, the tumor uptake could be blocked by co-injection of excess amount of unlabeled Annexin V protein. At day 7 after treatment, the tumor uptake of (18)F-Annexin had returned to baseline level.
  
  
  CONCLUSIONS
  (18)F-Annexin V PET imaging is sensitive enough to allow visualization of doxorubicin-induced cell death in UM-SCC-22B xenograft model. The longitudinal imaging with (18)F-Annexin will be helpful to monitor early response to chemotherapeutic anti-cancer drugs.
authors.affiliation: Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Hu
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Naoki
authors.initials: N
authors.lastname: Hida
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D017304:Annexin A5; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D013194:Staining and Labeling; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D017304:Annexin A5; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D004317:Doxorubicin