Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Tumor heterogeneity and genetic adaptation complicate cancer detection and treatment targeting specific mutations.
• Aberrant protein phosphorylation and calcium signaling are conserved hallmarks of cancer, offering potential therapeutic and diagnostic targets.

Purpose of the Study:

• To develop a novel imaging agent targeting broadly conserved cancer hallmarks.
• To investigate the potential of a cyclic octapeptide for selective tumor detection and drug delivery.

Main Methods:

• A near-infrared dye-labeled cyclic octapeptide was synthesized and tested for binding affinity to phosphorylated Annexin A2 (pANXA2) under varying calcium concentrations.
• The peptide's tumor-targeting capabilities were evaluated in mouse models with xenografts and metastatic lesions.
• Applications in fluorescence-guided surgery and drug delivery were demonstrated in proof-of-concept studies.

Main Results:

• The octapeptide selectively binds to pANXA2 with high affinity in the presence of elevated calcium levels.
• The peptide preferentially targets the invasive edges of tumors due to cancer-cell-induced pANXA2 expression in stromal cells.
• The peptide successfully detected tumor xenografts and metastatic lesions, and facilitated fluorescence-guided tumor resection in mice.

Conclusions:

• Elevated pANXA2 and calcium are prevalent in the microenvironment of most solid cancers, representing a viable therapeutic target.
• The developed octapeptide shows broad utility for selective tumor imaging and targeted drug delivery to tumor peripheries and core.
• This approach offers a promising strategy for overcoming limitations in current cancer detection and treatment modalities.