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

Abstract

PURPOSE: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([(11)C]docetaxel). The objective of this study was to investigate whether a [(11)C]docetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel. EXPERIMENTAL DESIGN: Docetaxel-naïve lung cancer patients underwent 2 [(11)C]docetaxel PET scans; one after bolus injection of [(11)C]docetaxel and another during combined infusion of [(11)C]docetaxel and a therapeutic dose of docetaxel (75 mg·m(-2)). Compartmental and spectral analyses were used to quantify [(11)C]docetaxel tumor kinetics. [(11)C]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 (Ki) of [(11)C]docetaxel in tumors were comparable during microdosing and therapeutic scans. [(11)C]docetaxel AUCTumor during the therapeutic scan could be predicted reliably using an impulse response function derived from the microdosing scan together with the plasma curve of [(11)C]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. [(11)C]docetaxel Ki derived from the microdosing scan correlated with AUCTumor of docetaxel (Spearman ρ = 0.715; P = 0.004) during the therapeutic scan and with tumor response to docetaxel therapy (Spearman ρ = -0.800; P = 0.010). CONCLUSIONS: Microdosing data of [(11)C]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.