Toward Prediction of Efficacy of Chemotherapy: A Proof of Concept Study in Lung Cancer Patients Using [11C]docetaxel and Positron Emission Tomography

Purpose: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([C-11]docetaxel). The objective of this study was to investigate whether a [C-11]docetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel. Experimental Design: Docetaxel-naive lung cancer patients underwent 2 [C-11]docetaxel PET scans; one after bolus injection of [C-11]docetaxel and another during combined infusion of [C-11]docetaxel and a therapeutic dose of docetaxel (75 mg.m(-2)). Compartmental and spectral analyses were used to quantify [C-11]docetaxel tumor kinetics. [C-11]docetaxel PET measurements were used to estimate the area under the curve (AUC) of docetaxel in tumors. Tumor response was evaluated using computed tomography scans. Results: Net rates of influx (K-i) of [C-11]docetaxel in tumors were comparable during microdosing and therapeutic scans. [C-11]docetaxel AUC(Tumor) during the therapeutic scan could be predicted reliably using an impulse response function derived from the microdosing scan together with the plasma curve of [C-11]docetaxel during the therapeutic scan. At 90 minutes, the accumulated amount of docetaxel in tumors was less than 1% of the total infused dose of docetaxel. [C-11]docetaxel K-i derived from the microdosing scan correlated with AUC(Tumor) of docetaxel (Spearman rho = 0.715; P = 0.004) during the therapeutic scan and with tumor response to docetaxel therapy (Spearman rho = -0.800; P = 0.010). Conclusions: Microdosing data of [C-11]docetaxel PET can be used to predict tumor uptake of docetaxel during chemotherapy. The present study provides a framework for investigating the PET microdosing concept for radiolabeled anticancer drugs in patients. (C) 2013 AACR.