Absolute quantification of [(11)C]docetaxel kinetics in lung cancer patients using positron emission tomography

Abstract

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 ([(11)C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [(11)C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [(11)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 [(11)C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [(11)C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated.

Results: Reproducible quantification of [(11)C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size ≥4 cm(3)) were identified, having a variable net influx rate of [(11)C]docetaxel (range, 0.0023-0.0229 mL·cm(-3)·min(-1)). [(11)C]docetaxel uptake was highly related to tumor perfusion (Spearman's ρ = 0.815;P < 0.001), but not to tumor size (Spearman's ρ = -0.140; P = 0.446). Patients pretreated with dexamethasone showed lower [(11)C]docetaxel uptake in tumors (P = 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [(11)C]docetaxel uptake was related with improved tumor response.

Conclusions: Quantification of [(11)C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [(11)C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [(11)C]docetaxel uptake and the effects of comedication on [(11)C]docetaxel kinetics in tumors.