Effects of erlotinib therapy on [11C]erlotinib uptake in EGFR mutated, advanced NSCLC

Idris Bahce, Maqsood Yaqub, Hanane Errami, Robert C. Schuit, Patrick Schober, Erik Thunnissen, Albert D. Windhorst, Adriaan A. Lammertsma, Egbert F. Smit, N. Harry Hendrikse

In non-small cell lung cancer (NSCLC) patients off erlotinib therapy, positron emission tomography (PET) using [(11)C]erlotinib distinguished epidermal growth factor receptor (EGFR) mutations from wild-type EGFR. However, tumor uptake of [(11)C]erlotinib during erlotinib therapy is unknown. Therefore, the aims of this study were to evaluate tumor [(11)C]erlotinib uptake in NSCLC patients both on and off erlotinib therapy, to evaluate the effect of erlotinib therapy on tumor perfusion and its correlation to tumor [(11)C]erlotinib uptake, and also, to investigate simplified uptake parameters using arterial and venous blood samples. Ten patients were to be scanned twice with a 1-2-week interval, i.e., on (E+) and off (E-) erlotinib therapy. Each procedure consisted of a low-dose CT scan, a 10-min dynamic [(15)O]H2O PET scan, and a 60-min dynamic [(11)C]erlotinib PET scan with arterial and venous sampling at six time points. In patients(E+), the optimal compartment model was analyzed using Akaike information criterion. In patients(E-), the uptake parameter was the volume of distribution (V T), estimated by using metabolite-corrected plasma input curves based on image-derived input functions and discrete arterial and venous blood samples. Tumor blood flow (TBF) was determined by rate constant of influx (K1) of [(15)O]H2O using the 1T2k model and correlated with V T and K1 values of [(11)C]erlotinib. The investigated simplified parameters were standardized uptake value (SUV) and tumor-to-blood ratio (TBR) at 40-60 min pi interval. Of the 13 patients included, ten were scanned twice. In patients(E+), [(11)C]erlotinib best fitted the 2T4k model with V T. In all patients, tumor V T(E+) was lower than V T(E-) (median V T(E-) = 1.61, range 0.77-3.01; median V T(E+) = 1.17, range 0.53-1.74; P = 0.004). Using [(15)O]H2O, five patients were scanned twice. TBF did not change with erlotinib therapy, TBF showed a positive trend towards correlation with [(11)C]erlotinib K1, but not with V T. TBR40-50 and TBR50-60, using both arterial and venous sampling, correlated with V T(E-) (all r s >0.9, P < 0.001), while SUV did not. In patients off and on therapy, venous TBR underestimated arterial TBR by 26 ± 12 and 9 ± 9 %, respectively. In patients on erlotinib in therapeutic dose, tumor V T decreases with high variability, independent of tumor perfusion. For simplification of [(11)C]erlotinib PET scanning protocols, both arterial and venous TBR 40-60 min post injection can be used; however, arterial and venous TBR values should not be interchanged as venous values underestimate arterial values. Registered at the Netherlands Trial Registry: NTR3670 .