TY - JOUR T1 - Monitoring Afatinib Treatment in HER2-Positive Gastric Cancer with <sup>18</sup>F-FDG and <sup>89</sup>Zr-Trastuzumab PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 936 LP - 943 DO - 10.2967/jnumed.112.110239 VL - 54 IS - 6 AU - Yelena Y. Janjigian AU - Nerissa Viola-Villegas AU - Jason P. Holland AU - Vadim Divilov AU - Sean D. Carlin AU - Erica M. Gomes-DaGama AU - Gabriela Chiosis AU - Gregory Carbonetti AU - Elisa de Stanchina AU - Jason S. Lewis Y1 - 2013/06/01 UR - http://jnm.snmjournals.org/content/54/6/936.abstract N2 - We evaluated the ability of the PET imaging agent 89Zr-trastuzumab to delineate HER2-positive gastric cancer and to monitor the pharmacodynamic effects of the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor afatinib. Methods: Using 89Zr-trastuzumab, 18F-FDG, or 3′-deoxy-3′-18F-fluorothymidine (18F-FLT PET), we imaged HER2-positive NCI-N87 and HER2-negative MKN74 gastric cancer xenografts in mice. Next, we examined the pharmacodynamic effects of afatinib in NCI-N87 xenografts using 89Zr-trastuzumab and 18F-FDG PET and comparing imaging results to changes in tumor size and in protein expression as monitored by Western blot and histologic studies. Results: Although 18F-FDG uptake in NCI-N87 tumors did not change, a decrease in 89Zr-trastuzumab uptake was observed in the afatinib-treated versus control groups (3.0 ± 0.0 percentage injected dose per gram (%ID/g) vs. 21.0 ± 3.4 %ID/g, respectively; P &lt; 0.05). 89Zr-trastuzumab PET results corresponded with tumor reduction, apoptosis, and downregulation of HER2 observed on treatment with afatinib. Downregulation of total HER2, phosphorylated (p)-HER2, and p-EGFR occurred within 24 h of the first dose of afatinib, with a sustained effect over 21 d of treatment. Conclusion: Afatinib demonstrated antitumor activity in HER2-positive gastric cancer in vivo. 89Zr-trastuzumab PET specifically delineated HER2-positive gastric cancer and can be used to measure the pharmacodynamic effects of afatinib. ER -