Utility of [18 F]FLT-PET to Assess Treatment Response in Trastuzumab-Resistant and Trastuzumab-Sensitive HER2-Overexpressing Human Breast Cancer Xenografts

Jennifer G. Whisenant, J. Oliver McIntyre, Todd E. Peterson, Hakmook Kang, Violeta Sánchez, H. Charles Manning, Carlos L. Arteaga, Thomas E. Yankeelov

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: 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.Procedures: 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.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalMolecular Imaging and Biology
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • Assessing treatment response
  • Breast cancer
  • HER2+ xenografts
  • Trastuzumab
  • [<sup>18</sup> F]FLT-PET

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

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