title: Development of [(11)C]erlotinib positron emission tomography for in vivo evaluation of EGF receptor mutational status.
abstract: OBJECTIVE
  To evaluate whether, in patients with non-small cell lung carcinoma (NSCLC), tumor uptake of [(11)C]erlotinib can be quantified and imaged using positron emission tomography and to assess whether the level of tracer uptake corresponds with the presence of activating tumor EGF receptor (EGFR) mutations.
  
  
  METHODS
  Ten patients with NSCLCs, five with an EGFR exon 19 deletion, and five without were scanned twice (test retest) on the same day with an interval of at least 4 hours. Each scanning procedure included a low-dose computed tomographic scan, a 10-minute dynamic [(15)O]H(2)O scan, and a 1-hour dynamic [(11)C]erlotinib scan. Data were analyzed using full tracer kinetic modeling. EGFR expression was evaluated using immunohistochemistry.
  
  
  RESULTS
  The quantitative measure of [(11)C]erlotinib uptake, that is, volume of distribution (V(T)), was significantly higher in tumors with activating mutations, that is, all with exon 19 deletions (median V(T), 1.76; range, 1.25-2.93), than in those without activating mutations (median V(T), 1.06; range, 0.67-1.22) for both test and retest data (P = 0.014 and P = 0.009, respectively). Good reproducibility of [(11)C]erlotinib V(T) was seen (intraclass correlation coefficient = 0.88). Intergroup differences in [(11)C]erlotinib uptake were not correlated with EGFR expression levels, nor tumor blood flow.
  
  
  CONCLUSIONS
  [(11)C]erlotinib V(T) was significantly higher in NSCLCs tumors with EGFR exon 19 deletions.
authors.affiliation: Departments of Pulmonary Diseases, VU University Medical Center, Amsterdam, Netherlands. i.bahce@vumc.nl
authors.forename: Idris
authors.initials: I
authors.lastname: Bahce
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Astrid A M
authors.initials: AA
authors.lastname: van der Veldt
authors.forename: Maqsood
authors.initials: M
authors.lastname: Yaqub
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: N Harry
authors.initials: NH
authors.lastname: Hendrikse
mesh_terms: D000328:Adult; D001483:Base Sequence; D002250:Carbon Radioisotopes / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009154:Mutation; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011799:Quinazolines / Q000737:chemistry / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed
chemical_list: D002250:Carbon Radioisotopes; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors