title: Absolute quantification of [(11)C]docetaxel kinetics in lung cancer patients using positron emission tomography.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands. aam.vanderveldt@vumc.nl
authors.forename: Astrid A M
authors.initials: AA
authors.lastname: van der Veldt
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Henri N
authors.initials: HN
authors.lastname: Greuter
authors.forename: Emile F I
authors.initials: EF
authors.lastname: Comans
authors.forename: Gerarda J M
authors.initials: GJ
authors.lastname: Herder
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.forename: Arthur
authors.initials: A
authors.lastname: van Lingen
authors.forename: S Nafees
authors.initials: SN
authors.lastname: Rizvi
authors.forename: Martien P J
authors.initials: MP
authors.lastname: Mooijer
authors.forename: Anneloes Y
authors.initials: AY
authors.lastname: Rijnders
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: N Harry
authors.initials: NH
authors.lastname: Hendrikse
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002250:Carbon Radioisotopes; D003907:Dexamethasone / Q000494:pharmacology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010477:Perfusion; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results; D043823:Taxoids / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D043823:Taxoids; D000077143:Docetaxel; D003907:Dexamethasone