[18F]-3′Deoxy-3′-Fluorothymidine Positron Emission Tomography and Breast Cancer Response to Docetaxel

Purpose: To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [F-18]-3'deoxy-3'-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer. Experimental Design: This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II-IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles). Results: Average and maximum tumor standardized uptake values at 60 minutes (SUV60,av and SUV60,max) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 x 10(-5) m(2)/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (P = 0.0003 for SUV60,av and P = 0.0002 for SUV60,max). Reduction in tumor SUV60,av was associated with target lesion size changes midtherapy (Pearson R for SUV60,av 0.64; P = 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV60,av in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, K-i). Docetaxel significantly reduced K-i by 51.1% (+/- 28.4%, P = 0.0009). Conclusion: Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non-FLT-PET response. Clin Cancer Res; 17(24); 7664-72. (C)2011 AACR.