3590 Background: Epidermal growth factor receptor (EGFR) plays a key role in tumorgenosis and is therefore an important target for new therapeutic and prognostic strategies. Our pilot study has demonstrated that 11C-PD153035, a highly EGFR selective tracer for positron emission tomography (PET), accumulated in tumor mass of non-small cell lung cancer (NSCLC) and the tracer uptake correlated with EGFR expression. Here, we further evaluate correlation between the intensity of 11C-PD153035 uptake and EGFR protein expression level and gene mutation. Methods: Fourteen patients (45–71y, mean 59.2±9.2 y, Male: Female = 8:6, squamous carcinoma: adenocarcinoma = 9:5) with pathologically proved NSCLC were examined with PET using 11C-PD153035 one week before surgery. Radioactivity concentrations, derived from regions of interest (ROI), were analyzed mathematically to maximum standardized uptake value (SUVmax). The EGFR protein expression of surgical specimen was utilized by immunohistochemistry (IHC) with a three-tier system intensity scored and Western Blot assay. The EGFR genetic alterations in exon 19 and 21 were examined by direct sequencing of polymerase chain reaction (PCR) products. Results: 11C-PD153035 uptake was observed in 9 out of 14 NSCLC patients (mean SUV 3.94±1.06, range 0.8–5.9) and the biodistribution study further demonstrated accumulation of radioactivity in the tumor mass. The SUVmax of 11C-PD153035 molecular images did not correlate with tumor size and injection dose of the tracer. A closely correlation between SUVmax and EGFR protein expression as determined by IHC (r = 0.84, p = 0.005) was observed but not with the protein expression level of Western Blot analysis (r = 0.442, p = 0.114), as well as EGFR exon 19 (r = -0.078, p = 0.790) or exon 21 (r = 0.118, p = 0.689) gene mutation. With ROC analysis according to IHC intensity, the cut-off value of SUVmax was 2.45. Conclusions: PET with 11C-PD153035 might therefore be used to visualize EGFR pattern on tumor in NSCLC patients and for individualized planning of therapeutic strategies with EGFR targeted drugs, especially small-molecule TKIs (gefitinib and erlotinib) which targeting the intracellular EGFR tyrosine kinase domain as PD153035. No significant financial relationships to disclose.
Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib