Development of [(11)C]erlotinib positron emission tomography for in vivo evaluation of EGF receptor mutational status

Idris Bahce*, Egbert F Smit, Mark Lubberink, Astrid A M van der Veldt, Maqsood Yaqub, Albert D Windhorst, Robert C Schuit, Erik Thunnissen, Daniëlle A M Heideman, Pieter E Postmus, Adriaan A Lammertsma, N Harry Hendrikse

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

108 Citations (Scopus)

Abstract

PURPOSE: 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.

EXPERIMENTAL DESIGN: 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.

CONCLUSION: [(11)C]erlotinib V(T) was significantly higher in NSCLCs tumors with EGFR exon 19 deletions.

Original languageEnglish
Pages (from-to)183-1993
Number of pages11
JournalClinical Cancer Research : an official journal of the American Association for Cancer Research
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

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