Related Experiment Video
Updated: May 30, 2026
Investigating Angiogenesis on a Functional and Molecular Level by Leveraging the Scratch Wound Migration Assay and the Spheroid Sprouting Assay
Published on: May 31, 2024
The development of peptide-based tools for the analysis of angiogenesis
Anna Fedorova1, Kerry Zobel, Herman S Gill
1Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA.
Abstract:
Limitations to the application of molecularly targeted cancer therapies are the inability to accurately match patient with effective treatment and the absence of a prompt readout of posttreatment response. Noninvasive agents that rapidly report vascular endothelial growth factor (VEGF) levels using positron emission tomography (PET) have the potential to enhance anti-angiogenesis therapies. Using phage display, two distinct classes of peptides were identified that bind to VEGF with nanomolar affinity and high selectivity. Co-crystal structures of these different peptide classes demonstrate that both bind to the receptor-binding region of VEGF. (18)F-radiolabelling of these peptides facilitated the acquisition of PET images of tumor VEGF levels in a HM7 xenograph model. The images obtained from one 59-residue probe, (18)F-Z-3B, 2 hr postinjection are comparable to those obtained with anti-VEGF antibody B20 72 hr postinjection. Furthermore, VEGF levels in growing SKOV3 tumors were followed using (18)F-Z-3B as a PET probe with VEGF levels increasing with tumor size.
Insights
New positron emission tomography (PET) imaging agents can now track vascular endothelial growth factor (VEGF) levels in tumors. This breakthrough aids in matching cancer patients with targeted therapies and monitoring treatment response.
Area of Science:
- Oncology
- Molecular Imaging
- Biotechnology
Background:
- Molecularly targeted cancer therapies face challenges in patient selection and prompt response assessment.
- Anti-angiogenesis therapies require methods to monitor treatment efficacy.
- Noninvasive imaging of vascular endothelial growth factor (VEGF) can potentially improve anti-angiogenesis therapy.
Purpose of the Study:
- To develop novel positron emission tomography (PET) imaging agents for noninvasive detection of tumor vascular endothelial growth factor (VEGF).
- To assess the potential of these agents in matching patients to effective treatments and monitoring therapeutic response.
Main Methods:
- Phage display was employed to identify peptides with high affinity and selectivity for VEGF.
- Co-crystal structures were determined to understand the binding mechanism of the identified peptides.
- Fluorine-18 ((18)F) radiolabeling was performed for PET imaging of tumor VEGF levels in a xenograph model.
Main Results:
- Two distinct classes of peptides binding to VEGF with nanomolar affinity were discovered.
- Co-crystal structures revealed that both peptide classes bind to the receptor-binding region of VEGF.
- The (18)F-radiolabeled peptide (18)F-Z-3B enabled PET imaging of tumor VEGF levels, comparable to antibody B20 at an earlier time point.
- VEGF levels in SKOV3 tumors correlated with tumor size, as visualized by (18)F-Z-3B PET imaging.
Conclusions:
- Novel (18)F-labeled peptides targeting VEGF were successfully developed for PET imaging.
- These PET probes offer a rapid, noninvasive method to assess tumor VEGF levels and monitor anti-angiogenesis therapy response.
- The findings support the clinical utility of these agents for personalized cancer treatment strategies.
Related Concept Videos
01:10Mechanism of Angiogenesis
01:24Regulation of Angiogenesis and Blood Supply