Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a 99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability

作     者：Hao Liu Liquan Gao Xinhe Yu Lijun Zhong Jiyun Shi Bing Jia Nan Li Zhaofei Liu Fan Wang 

作者机构：Medical Isotopes Research Center and Department of Radiation Medicine School of Basic Medical Sciences Peking University Health Science Center Medical and Healthy Analytical Center Peking University Key Laboratory of Protein and Peptide Pharmaceuticals CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Department of Nuclear Medicine Peking University Cancer Hospital & Institute 

出 版 物：《Biophysics Reports》 (生物物理学报(英文))

年 卷 期：2018年第4卷第5期

页      面：254-264页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100106[医学-放射医学] 10[医学] 

基　　金：partially supported by the National Key R&D Program of China (2018YFC1313300 and 2017YFA0205600) the National Natural Science Foundation of China (81471712, 81671747, 81630045, 81873907, and 81420108019) the Beijing Natural Science Foundation (L172007) the Beijing Nova Program Interdisciplinary Cooperation Project (Z181100006218136) the Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2018LCXQ017) 

主　　题：Integrin αvβ6 Molecular imaging Pancreatic cancer Peptide cyclization Pulmonary fibrosis Single-photon emission computed tomography (SPECT) 

摘      要：Integrin αvβ6 is expressed at an undetectable level in normal tissues,but is remarkably upregulated during many pathological processes,especially in cancer and *** imaging of integrin αvβ6 expression using a radiotracer with favorable in vivo pharmacokinetics would facilitate disease diagnosis and therapy *** disulfide-cyclized method,we synthesized in this study,a new integrin avb6-targeted cyclic peptide (denoted as cHK),and radiolabeled it *** ability of the resulting radiotracer99mTc–HYNIC–cHK to detect integrin αvβ6 expression in pancreatic cancer xenografts and idiopathic pulmonary fibrosis was evaluated using small-animal single-photon emission computed tomography (SPECT)/computed tomography (CT).99mTc–HYNIC–cHK showed significantly improved in vivo metabolic stability compared to the linear peptide-based radiotracer99mTc–HYNIC–HK.99mTc–HYNIC–cHK exhibited similar biodistribution properties to99mTc–HYNIC–HK,but the tumorto-muscle ratio was significantly increased (2.99±0.87 vs.1.82±0.27,P\0.05).High-contrast images of integrin avb6-positive tumors and bleomycin-induced fibrotic lungs were obtained by SPECT/CT imaging using99mTc–HYNIC–***,our studies demonstrate that99mTc–HYNIC–cHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 in living subjects.