@article {Janjigian936, author = {Yelena Y. Janjigian and Nerissa Viola-Villegas and Jason P. Holland and Vadim Divilov and Sean D. Carlin and Erica M. Gomes-DaGama and Gabriela Chiosis and Gregory Carbonetti and Elisa de Stanchina and Jason S. Lewis}, title = {Monitoring Afatinib Treatment in HER2-Positive Gastric Cancer with 18F-FDG and 89Zr-Trastuzumab PET}, volume = {54}, number = {6}, pages = {936--943}, year = {2013}, doi = {10.2967/jnumed.112.110239}, publisher = {Society of Nuclear Medicine}, abstract = {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 {\textpm} 0.0 percentage injected dose per gram (\%ID/g) vs. 21.0 {\textpm} 3.4 \%ID/g, respectively; P \< 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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/54/6/936}, eprint = {https://jnm.snmjournals.org/content/54/6/936.full.pdf}, journal = {Journal of Nuclear Medicine} }