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

Autor:	van der Veldt AA; Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands. aam.vanderveldt@vumc.nl, Lubberink M, Greuter HN, Comans EF, Herder GJ, Yaqub M, Schuit RC, van Lingen A, Rizvi SN, Mooijer MP, Rijnders AY, Windhorst AD, Smit EF, Hendrikse NH, Lammertsma AA
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2011 Jul 15; Vol. 17 (14), pp. 4814-24. Date of Electronic Publication: 2011 Jul 12.
DOI:	10.1158/1078-0432.CCR-10-2933
Abstrakt:	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.
Databáze:	MEDLINE
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