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Ref Type | Journal Article | ||||||||||||
PMID | (23578997) | ||||||||||||
Authors | Janjigian YY, Viola-Villegas N, Holland JP, Divilov V, Carlin SD, Gomes-DaGama EM, Chiosis G, Carbonetti G, de Stanchina E, Lewis JS | ||||||||||||
Title | Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and 89Zr-trastuzumab PET. | ||||||||||||
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Abstract Text | We evaluated the ability of the PET imaging agent (89)Zr-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.Using (89)Zr-trastuzumab, (18)F-FDG, or 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-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 (89)Zr-trastuzumab and (18)F-FDG PET and comparing imaging results to changes in tumor size and in protein expression as monitored by Western blot and histologic studies.Although (18)F-FDG uptake in NCI-N87 tumors did not change, a decrease in (89)Zr-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 < 0.05). (89)Zr-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.Afatinib demonstrated antitumor activity in HER2-positive gastric cancer in vivo. (89)Zr-trastuzumab PET specifically delineated HER2-positive gastric cancer and can be used to measure the pharmacodynamic effects of afatinib. |
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