期刊
JOURNAL OF NUCLEAR MEDICINE
卷 55, 期 6, 页码 1002-1007出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.114.137000
关键词
molecular imaging; EGFR; HER2; immunotherapy; tumor response
资金
- National Natural Science Foundation of China (NSFC) [81222019, 81125011, 30930030, 81000625, 81201127]
- 973 projects [2013CB733802, 2011CB707703]
- Ministry of Science and Technology of China [2011YQ030114, 2012ZX09102301-018, 2012BA1C25B03-16]
- Ministry of Education of China [31300, BMU20110263]
- Beijing Natural Science Foundation [7132131, 7132123]
- Beijing Nova Program [Z121107002512010]
Previous in vitro studies demonstrated that treating tumors expressing both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 with trastuzumab resulted in increased EGFR homodimerization and subsequent rapid downregulation of EGFR. We investigated whether molecular imaging using near-infrared fluorescence (NIRF) imaging and PET probes could sensitively detect trastuzumab-induced EGFR downregulation in vivo. Methods: The F(ab')2 antibody fragment PaniF(ab')(2) was generated by digesting the anti-EGFR monoclonal antibody panitumumab. PaniF(ab')(2) was labeled with either a NIRF dye or Ga-68, and optical imaging and small-animal PET imaging of Dye-PaniF(ab')(2) and Ga-68-PaniF(ab')(2), respectively, were performed in HT-29 tumor bearing nude mice treated with trastuzumab or untreated control. Results: Longitudinal NIRF imaging studies revealed significantly reduced tumor uptake of Dye-PaniF(ab')(2) on days 5 and 7 in trastuzumab-treated HT-29 tumors, compared with control. Western blotting confirmed the downregulation of EGFR after treatment with trastuzumab. Small-animal PET on day 5 after trastuzumab treatment also demonstrated decreased Ga-68-PaniF(ab')(2) uptake in trastuzumab-treated HT-29 tumors. The tumor uptake value of Ga-68-PaniF(ab')(2) obtained from PET imaging had an excellent linear correlation with the uptake value measured using biodistribution. Conclusion: The downregulation of EGFR induced by trastuzumab treatment could be detected noninvasively using optical and PET imaging. This molecular imaging strategy could provide a dynamic readout of changes in the tumor signaling and may facilitate the noninvasive monitoring of the early tumor response to drug treatment.
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