Abstract
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 68Ga, and optical imaging and small-animal PET imaging of Dye-PaniF(ab′)2 and 68Ga-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 68Ga-PaniF(ab′)2 uptake in trastuzumab-treated HT-29 tumors. The tumor uptake value of 68Ga-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.
Footnotes
Published online Apr. 14, 2014.
- © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.