Early prediction of antiepidermal growth factor receptor therapy with 18[F]FDG-PET: A preclinical and clinical correlation.

B35

Background. The ability to predict response to anti-epidermal growth factor receptor (EGFR) therapy is pivotal to individualized cancer treatment. We hypothesized that early changes in 18[F]FDG tumor uptake predicts response to anti-EGFR therapy. We investigated this question in a mice model and correlated these findings in human patients undergoing anti-EGFR therapy. Methods. Mice bearing erlotinib-resistant (Hep2) and -sensitive (Cal27) head and neck squamous cell cancer (HNSCC) xenografts were treated with vehicle or erlotinib for 3 weeks. Uptake of 18[F]FDG were imaged with small animal micro-PET at baseline and after 1 week of therapy, and reported in SUVmax. For clinical correlation, human patients with HNSCC receiving erlotinib were identified from an ongoing clinical trial. Clinical 18[F]FDG-PET images were obtained at baseline and after 2 weeks of erlotinib monotherapy. Both xenograft and human tumor specimens were obtained at baseline and when follow-up PET scans were performed. A panel of pharmacodynamic markers (including Ki-67 and pMAPK) were assessed. Results. The Hep2 xenografts were resistant to erlotinib (Tumor/Control ratio [T/C]: 0.8) and Cal27 was sensitive (T/C: 0.2). In the resistant Hep2 xenografts, the SUVmax increased significantly from baseline after treatment and was not significantly different from the control tumors (86% of control; +/- 70%). In the sensitive Cal27 xenografts, the SUVmax remained stable from baseline and was significantly lower than control (-2% of control; +/-7%). Ki-67 in the treated Hep2 was not significantly different from control while that in Cal27 was <50% of control. In the clinical cases, the ki-67 score was higher after 2 weeks from baseline in the patient resistant to erlotinib monotherapy by 18[F]FDG-PET (SUVmax increased by 14%; +/- 11%) while the proliferative index was lower than baseline in the patient who was 18[F]FDG-PET sensitive (SUVmax decreased by 56%; +/- 13%). pMAPK decreased after 2 weeks of erlotinib therapy in all cases and had a poor correlation with efficacy. Conclusions. Early dynamic changes in 18[F]FDG tumor uptake is predictive of response to anti-EGFR therapy and correlates with changes in ki-67 expression, both in a preclinical and a clinical scenario. This study demonstrated the feasibility and provides the rationale for the use of small animal FDG-PET imaging in the development of targeted agents and individualized therapy.