title: In vivo phage display selection of an ovarian cancer targeting peptide for SPECT/CT imaging.
abstract: 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 (111)In. 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 (111)In-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 (111)In-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.
authors.affiliation: Department of Biochemistry, University of Missouri Rm117 Schweitzer Hall, Columbia, MO 65211.
authors.forename: Mette
authors.initials: M
authors.lastname: Soendergaard
authors.affiliation: Department of Biochemistry, University of Missouri Rm117 Schweitzer Hall, Columbia, MO 65211.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Newton-Northup
authors.affiliation: Department of Biochemistry, University of Missouri Rm117 Schweitzer Hall, Columbia, MO 65211 ; Harry S. Truman Memorial Veterans Hospital, 1 Hospital Drive Columbia, MO 65201.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Deutscher
keywords: Ovarian cancer; SPECT imaging; peptide; phage display