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

Purpose: The objective of this study was to evaluate 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]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 similar to 50 % less in trastuzumab-sensitive xenografts. Conclusions: [F-18]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.