In vivo phage display selection of an ovarian cancer targeting peptide for SPECT/CT imaging

American Journal of Nuclear Medicine and Molecular Imaging

Susan L Deutscher¹  Mette Soendergaard¹  Jessica R Newton-Northup¹ 

关键词: Ovarian cancer;    peptide;    phage display;    SPECT imaging;   

DOI  :  

学科分类：过敏症与临床免疫学

来源: e-Century Publishing Corporation

【 摘 要 】

The often fatal outcome of ovarian cancer (OC) is related to inadequate detection methods, which may be overcome by development of nuclear imaging agents. Cancer targeting peptides have been identified using in vivo bacteriophage (phage) display technology; however, the majority of these ligands target tumor vasculature. To overcome this problem, a two-tier phage display method was employed to select an ovarian cancer targeting peptide with good pharmacokinetic and imaging properties. A fUSE5 15-amino acid peptide library was screened against xenografted human OC SKOV-3 tumors in mice, which was followed by selection against enriched SKOV-3 cells. The selected peptide RSLWSDFYASASRGP (J18) was synthesized with a GSG-spacer and a 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) chelator and radiolabeled with ¹¹¹In. SKOV-3 xenografted mice were used to evaluate the biodistribution and single photon emission computed tomography (SPECT) imaging capabilities of the radiolabeled peptide. Competitive binding experiments using ¹¹¹In-DOTA-GSG-J18 indicated that the peptide displayed a half maximal inhibitory concentration (IC₅₀) value of 10.5 ± 1.1 μM. Biodistribution studies revealed that tumor uptake was 1.63 ± 0.68, 0.60 ± 0.32, 0.31 ± 0.12 and 0.10 ± 0.02% injected dose/g at 30 min, 1 h, 2 h and 4 h post-injection of ¹¹¹In-DOTA-GSG-J18, respectively. SPECT/CT imaging demonstrated good tumor uptake and minimal background binding. This study demonstrated successful utilization of a two-tier phage display selection process to identify an ovarian cancer avid peptide with excellent SPECT/CT imaging capabilities.

【 授权许可】

Unknown