Purpose: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([11C]docetaxel). The objective of this study was to investigate whether a [11C]docetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel. Experimental Design: Docetaxel-näve lung cancer patients underwent 2 [11C]docetaxel PET scans; one after bolus injection of [11C]docetaxel and another during combined infusion of [11C]docetaxel and a therapeutic dose of docetaxel (75 mgm 2). Compartmental and spectral analyses were used to quantify [11C]docetaxel tumor kinetics. [11C]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 [11C]docetaxel in tumors were comparable during microdosing and therapeutic scans. [11C]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 [11C]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. [11C]docetaxel Ki derived from the microdosing scan correlated with AUCTumor of docetaxel (Spearman r = 0.715; P = 0.004) during the therapeutic scan and with tumor response to docetaxel therapy (Spearman r = 0.800; P = 0.010). Conclusions: Microdosing data of [11C]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.

doi.org/10.1158/1078-0432.CCR-12-3779, hdl.handle.net/1765/70656
Clinical Cancer Research
Department of Medical Oncology

van der Veldt, A., Lubberink, M., Mathijssen, R., Loos, W., Herder, G. J. M., Greuter, M., … Lammertsma, A. (2013). Toward prediction of efficacy of chemotherapy: A proof of concept study in lung cancer patients using [11C]docetaxel and positron emission tomography. Clinical Cancer Research, 19(15), 4163–4173. doi:10.1158/1078-0432.CCR-12-3779