Imaging Early-Stage Metastases Using an ¹⁸F-Labeled VEGFR-1-Specific Single Chain VEGF Mutant

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Metastatic breast cancer is a leading cause of cancer death with a persistent low survival rate.
• Early detection of metastasis is crucial for effective treatment and improved patient outcomes.
• Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) is implicated in metastasis formation.

Purpose of the Study:

• To develop and evaluate an 18F-labeled positron emission tomography (PET) imaging agent for non-invasive detection of early-stage breast cancer metastases.
• To create a single-chain antibody fragment (scVR1) targeting VEGFR-1 for improved metastatic imaging.
• To assess the diagnostic potential of the novel [18F]AlF-NODA-scVR1 tracer in preclinical models.

Main Methods:

• 18F-labeling of scVR1 using a click reaction with Al18F-labeled tetrazine-NODA.
• Purification and radiochemical purity analysis of the [18F]AlF-NODA-scVR1 tracer.
• PET imaging and ex vivo biodistribution studies in murine models with orthotopic tumors or metastatic lesions.

Main Results:

• The [18F]AlF-NODA-scVR1 tracer was prepared with high radiochemical purity (>98%) and specific binding to VEGFR-1.
• PET imaging demonstrated clear visualization of tumor uptake and metastatic lesions in mice.
• Ex vivo analysis confirmed tracer colocalization with metastatic sites and VEGFR-1 expression.

Conclusions:

• The [18F]AlF-NODA-scVR1 PET tracer demonstrated diagnostic capability in preclinical models of breast cancer metastasis.
• This novel tracer shows promise for non-invasively imaging metastases.
• It could serve as a valuable tool for clinicians to guide adjuvant therapy decisions in breast cancer patients.