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

Background: In non-small cell lung cancer (NSCLC) patients off erlotinib therapy, positron emission tomography (PET) using [C-11]erlotinib distinguished epidermal growth factor receptor (EGFR) mutations from wild-type EGFR. However, tumor uptake of [C-11]erlotinib during erlotinib therapy is unknown. Therefore, the aims of this study were to evaluate tumor [C-11]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 [C-11]erlotinib uptake, and also, to investigate simplified uptake parameters using arterial and venous blood samples. Methods: 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 [O-15]H2O PET scan, and a 60-min dynamic [C-11]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 [O-15]H2O using the 1T2k model and correlated with V-T and K1 values of [C-11]erlotinib. The investigated simplified parameters were standardized uptake value (SUV) and tumor-to-blood ratio (TBR) at 40-60 min pi interval. Results: Of the 13 patients included, ten were scanned twice. In patients(E+), [C-11]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 [O-15]H2O, five patients were scanned twice. TBF did not change with erlotinib therapy, TBF showed a positive trend towards correlation with [C-11]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. Conclusions: In patients on erlotinib in therapeutic dose, tumor V-T decreases with high variability, independent of tumor perfusion. For simplification of [C-11]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.