Jennifer G. Whisenant (1) (2), J. Oliver McIntyre (1) (2) (3), Todd E. Peterson (1) (2) (4), Hakmook Kang (5), Violeta Sánchez (10), H. Charles Manning (1) (10) (2) (6) (7), Carlos L. Arteaga (3) (8) (9), Thomas E. Yankeelov 
(1) (10) (2) (3) (4) (6)
1. Institute of Imaging Science, Vanderbilt University, 1161 21st Ave. South, MCN AA-1105, Nashville, TN, 37232-2675, USA
2. Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, 37232-2675, USA
3. Department of Cancer Biology, Vanderbilt University, Nashville, TN, 37232-2675, USA
4. Department of Physics, Vanderbilt University, Nashville, TN, 37232-2675, USA
5. Department of Biostatistics, Vanderbilt University, Nashville, TN, 37232-2675, USA
10. Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, 37232-2675, USA
6. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232-2675, USA
7. Department of Neurological Surgery, Vanderbilt University, Nashville, TN, 37232-2675, USA
8. Department of Medicine, Vanderbilt University, Nashville, TN, 37232-2675, USA
9. Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, 37232-2675, USA
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.