Absolute Quantification of [C]docetaxel Kinetics in Lung Cancer Patients Using Positron Emission Tomography

Purpose: Tumor resistance to docetaxel may be associated with reduced drug concentrations in tumor tissue. Positron emission tomography (PET) allows for quantification of radiolabeled docetaxel ([C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [C]docetaxel kinetics were associated with tumor perfusion, tumor size, and dexamethasone administration. Experimental Design: Thirty-four lung cancer patients underwent dynamic PET–computed tomography (CT) scans using [C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated. Results: Reproducible quantification of [C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size 4 cm) were identified, having a variable net influx rate of [C]docetaxel (range, 0.0023–0.0229mL cm 3 min ). [C]docetaxel uptake was highly related to tumor perfusion (Spearman’s r 1⁄4 0.815; P < 0.001), but not to tumor size (Spearman’s r 1⁄4 0.140; P 1⁄4 0.446). Patients pretreated with dexamethasone showed lower [C]docetaxel uptake in tumors (P1⁄4 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [C]docetaxel uptake was related with improved tumor response. Conclusions: Quantification of [C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [C]docetaxel uptake and the effects of comedication on [C]docetaxel kinetics in tumors. Clin Cancer Res; 17(14); 4814–24. 2011 AACR.