Teng Ma1, Xianlei Sun1, Liyang Cui1, Liquan Gao1, Yue Wu1, Hao Liu1, Zhaohui Zhu2, Fan Wang1, Zhaofei Liu3. 1. Medical Isotopes Research Center, Peking University, Beijing, China Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; and. 2. Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China. 3. Medical Isotopes Research Center, Peking University, Beijing, China Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; and liuzf@bjmu.edu.cn.
Abstract
UNLABELLED: 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 (68)Ga, and optical imaging and small-animal PET imaging of Dye-PaniF(ab')2 and (68)Ga-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 (68)Ga-PaniF(ab')2 uptake in trastuzumab-treated HT-29 tumors. The tumor uptake value of (68)Ga-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.
UNLABELLED: Previous in vitro studies demonstrated that treating tumors expressing both epidermal growth factor receptor (EGFR) and humanepidermal 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 (68)Ga, and optical imaging and small-animal PET imaging of Dye-PaniF(ab')2 and (68)Ga-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 (68)Ga-PaniF(ab')2 uptake in trastuzumab-treated HT-29 tumors. The tumor uptake value of (68)Ga-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.
Authors: Zhengyuan Zhou; Ganesan Vaidyanathan; Darryl McDougald; Choong Mo Kang; Irina Balyasnikova; Nick Devoogdt; Angeline N Ta; Brian R McNaughton; Michael R Zalutsky Journal: Mol Imaging Biol Date: 2017-12 Impact factor: 3.488
Authors: Jonathan G Sham; Forrest M Kievit; John R Grierson; Peter A Chiarelli; Robert S Miyaoka; Miqin Zhang; Raymond S Yeung; Satoshi Minoshima; James O Park Journal: J Nucl Med Date: 2014-10-30 Impact factor: 10.057