Jipeng Yin1, Xiaoli Hui2, Liping Yao1, Ming Li1, Hao Hu1, Jing Zhang1, Bo Xin3, Minglei He4, Jing Wang5, Yongzhan Nie1, Kaichun Wu6. 1. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. 2. First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China. 3. The 88th Hospital of PLA, Taian, China. 4. School of Life Science, Dalian Nationalities University, Dalian, China. 5. Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China. 6. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. kaicwu@fmmu.edu.cn.
Abstract
PURPOSE: This study aimed to evaluate the potential of PEGylated dimeric GX1 peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo tumor xenografted mouse model. PROCEDURES: The [(99m)Tc]PEG-(GX1)2 peptide was synthesized and identified. Confocal immunofluorescence analysis, receptor binding assay, and competitive inhibition assay were performed to evaluate the binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human umbilical vein endothelial cells (HUVECs). Single photon emission computed tomography imaging and biodistribution were performed to evaluate the targeting ability of PEG-(GX1)2 to colorectal cancer. RESULTS: The studies in vitro suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity. The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was superior to GX1. CONCLUSIONS: PEGylation improved the affinity and the targeting ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of colorectal vasculature than GX1.
PURPOSE: This study aimed to evaluate the potential of PEGylated dimeric GX1 peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo tumor xenografted mouse model. PROCEDURES: The [(99m)Tc]PEG-(GX1)2 peptide was synthesized and identified. Confocal immunofluorescence analysis, receptor binding assay, and competitive inhibition assay were performed to evaluate the binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human umbilical vein endothelial cells (HUVECs). Single photon emission computed tomography imaging and biodistribution were performed to evaluate the targeting ability of PEG-(GX1)2 to colorectal cancer. RESULTS: The studies in vitro suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity. The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was superior to GX1. CONCLUSIONS: PEGylation improved the affinity and the targeting ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of colorectal vasculature than GX1.