In vivo phage display selection of an ovarian cancer targeting peptide for SPECT/CT imaging
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Published on: September 30, 2019
Mette Soendergaard1, Jessica R Newton-Northup1, Susan L Deutscher2
1Department of Biochemistry, University of Missouri Rm117 Schweitzer Hall, Columbia, MO 65211.
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.
Insights
Researchers developed a novel ovarian cancer imaging agent using a two-tier phage display. This new peptide, J18, shows excellent tumor targeting and SPECT/CT imaging capabilities for early ovarian cancer detection.
Area of Science:
- Biomedical imaging
- Molecular imaging
- Oncology
Background:
- Ovarian cancer (OC) detection remains a challenge, often leading to fatal outcomes.
- Current nuclear imaging agents frequently target tumor vasculature, not the cancer cells directly.
- Phage display technology offers a method for identifying cancer-targeting peptides.
Purpose of the Study:
- To develop a novel nuclear imaging agent for ovarian cancer.
- To identify a peptide with high affinity for ovarian cancer cells and favorable imaging properties.
- To evaluate the diagnostic potential of the developed agent using SPECT/CT.
Main Methods:
- A two-tier phage display selection process was employed against human OC SKOV-3 xenografts and cells.
- The selected peptide (J18) was synthesized with a DOTA chelator and radiolabeled with Indium-111 ((111)In).
- Biodistribution and SPECT/CT imaging were performed in mice bearing SKOV-3 xenografts.
Main Results:
- A specific ovarian cancer-targeting peptide, J18 (RSLWSDFYASASRGP), was identified.
- Radiolabeled (111)In-DOTA-GSG-J18 demonstrated good tumor uptake and minimal background signal in SPECT/CT imaging.
- Competitive binding assays showed a half maximal inhibitory concentration (IC50) of 10.5 ± 1.1 μM for the peptide.
Conclusions:
- The two-tier phage display method successfully identified an ovarian cancer-avid peptide (J18).
- The radiolabeled peptide exhibits promising characteristics for SPECT/CT imaging of ovarian cancer.
- This approach holds potential for improving early detection and diagnosis of ovarian cancer.
