Monitoring afatinib treatment in HER2-positive gastric cancer with (18)F-FDG and (89)Zr-trastuzumab PET Journal Article

   


Authors: Janjigian, Y. Y.; Viola-Villegas, N.; Holland, J. P.; Divilov, V.; Carlin, S. D.; Gomes DaGama, E. M.; Chiosis, G.; Carbonetti, G.; de Stanchina, E.; Lewis, J. S.
Article Title: Monitoring afatinib treatment in HER2-positive gastric cancer with (18)F-FDG and (89)Zr-trastuzumab PET
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 ± 0.0 percentage injected dose per gram (%ID/g) vs. 21.0 ± 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. Copyright © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Keywords: her2; gastric cancer; 18f-fdg; afatinib; 89zr-trastuzumab
Journal Title: Journal of Nuclear Medicine
Volume: 54
Issue: 6
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2013-06-01
Start Page: 936
End Page: 943
Language: English
DOI: 10.2967/jnumed.112.110239
PROVIDER: scopus
PUBMED: 23578997
PMCID: PMC4967936
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84878663006&partnerID=40&md5=aa00240f4734dc4a6916b8979eec62d9
Notes: --- - "Export Date: 1 July 2013" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Yelena Yuriy Janjigian
    400 Janjigian
  2. Jason Philip Holland
    31 Holland
  3. Erica M. Gomes-Dagama
    15 Gomes-Dagama
  4. Nerissa Therese V Villegas
    14 Villegas
  5. Gabriela Chiosis
    279 Chiosis
  6. Elisa De Stanchina
    352 De Stanchina
  7. Jason S Lewis
    461 Lewis
  8. Sean Denis Carlin
    83 Carlin
  9. Vadim Divilov
    16 Divilov
  10. Gregory Carbonetti
    6 Carbonetti
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