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

• 来源期刊: 生物物理学报
• 年，卷（期）: 2018,（5）
• 页码范围: 254-264
• 页数: 11页
• 语种: 中文

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 fibrosis.Noninvasive imaging of integrin αvβ6 expression using a radiotracer with favorable in vivo pharmacokinetics would facilitate disease diagnosis and therapy monitoring.Through disulfide-cyclized method,we synthesized in this study,a new integrin αvβ6-targeted cyclic peptide (denoted as cHK),and radiolabeled it with 99mTC.The ability of the resulting radiotracer 99mTc-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 radiotracer 99mTc-HYNIC-HK.99mTc-HYNIC-cHK exhibited similar biodistribution properties to 99mTc-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 αvβ6-positive tumors and bleomycin-induced fibrotic lungs were obtained by SPECT/CT imaging using 99mTc-HYNIC-cHK.Overall,our studies demonstrate that 99mTc-HYNIC-cHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 in living subjects.