title: Utility of [18 F]FLT-PET to assess treatment response in trastuzumab-resistant and trastuzumab-sensitive HER2-overexpressing human breast cancer xenografts.
abstract: OBJECTIVE
  The objective of this study was to evaluate 3'-deoxy-3'-[(18) F]fluorothymidine ([(18) F]FLT) positron emission tomography (PET) as an early marker of trastuzumab response in HER2-overexpressing xenografts.
  
  
  METHODS
  Tumor-to-muscle ratios were compared between both trastuzumab-sensitive and trastuzumab-resistant cohorts prior to and after one and two treatments.
  
  
  RESULTS
  A significant difference (P = 0.03) was observed between treated and control trastuzumab-sensitive xenografts after one treatment, which preceded between-group differences in tumor volume. Reduced Ki67 (P = 0.02) and thymidine kinase 1 (TK1) (P = 0.35) immunoreactivity was observed in the treated xenografts. No significant differences in volume, tumor-to-muscle ratio, or immunoreactivity were observed between treated and control trastuzumab-resistant cohorts. A significant difference (P = 0.02) in tumor-to-muscle ratio was observed between trastuzumab-sensitive and trastuzumab-resistant cohorts after two treatments; however, tumor volumes were also different (P = 0.04). Ki67 (P = 0.04) and TK1 (P = 0.24) immunoreactivity was ~50 % less in trastuzumab-sensitive xenografts.
  
  
  CONCLUSIONS
  [(18) F]FLT-PET provided early response assessment in trastuzumab-sensitive xenografts but only differentiated between trastuzumab-resistant and trastuzumab-sensitive xenografts concurrent with differences in tumor size.
authors.affiliation: Institute of Imaging Science, Vanderbilt University, 1161 21st Ave. South, MCN AA-1105, Nashville, TN, 37232-2675, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Whisenant
authors.forename: J Oliver
authors.initials: JO
authors.lastname: McIntyre
authors.forename: Todd E
authors.initials: TE
authors.lastname: Peterson
authors.forename: Hakmook
authors.initials: H
authors.lastname: Kang
authors.forename: Violeta
authors.initials: V
authors.lastname: Sánchez
authors.forename: H Charles
authors.initials: HC
authors.lastname: Manning
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Arteaga
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D015224:Dideoxynucleosides / Q000737:chemistry*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C002854:alovudine