Chapter 7 Towards prediction of efficacy of chemotherapy : a proof of concept study in lung cancer using [ 11 C ] docetaxel and positron emission tomography

Background: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and [C]docetaxel. The objective of this study was to investigate whether a tracer [ Methods: Docetaxel-naïve lung cancer patients underwent two [ C]docetaxel PET study could predict tumor uptake of unlabeled (cold) docetaxel during a therapeutic infusion. C]docetaxel PET scans; one after bolus injection of [C]docetaxel and another during combined infusion of [C]docetaxel and a therapeutic dose of docetaxel (75 mg·m). Compartmental and spectral analyses were used to quantify [C]docetaxel tumor kinetics. [ Results: Net rates of influx (K C]docetaxel PET measurements were used to estimate the area under the curve (AUC) of cold docetaxel in tumors. Tumor response was evaluated using computed tomography scans. i) of [C]docetaxel in tumors were comparable during microdosing and therapeutic scans. [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 [C]docetaxel during the therapeutic scan. At 90 min, the accumulated amount of cold docetaxel in tumors was < 1% of the total infused dose of docetaxel. [C]docetaxel Ki derived from the microdosing scan correlated with AUCTumor Conclusions: Microdosing data of [ of cold docetaxel (Spearman’ = 0.715; P = 0.004) during the therapeutic scan and with tumor = -0.800; P = 0.010). 11 C]docetaxel PET can be used to predict tumor uptake of cold docetaxel during chemotherapy. The present study provides a framework for investigating the PET microdosing concept for radiolabeled anticancer drugs in patients. INTRODUCTION Docetaxel belongs to the class of taxanes, which act by disrupting the microtubular network that is essential for mitosis (1). Initially, the drug was approved as single agent for the treatment of anthracycline refractory advanced breast cancer (2). Thereafter, docetaxel has been approved both as single agent and in combination therapy to treat several advanced malignancies including gastric, head and neck, prostate and non-small cell lung cancer (3). Nevertheless, docetaxel fails to exert antitumor activity in a substantial number of patients and it is associated with potentially severe toxicities. Hence, there is a need for a tool to predict efficacy of docetaxel in individual patients. The response to docetaxel treatment is thought to be directly related to drug concentrations in tumor tissue. As a direct relationship between plasma concentration