Heterobivalent agents targeting PSMA and integrin-αvβ3

Area of Science:

• Biomedical imaging
• Cancer diagnostics
• Molecular targeting

Background:

• Differential surface protein expression between normal and malignant cells is key for targeted cancer therapies.
• Tumor heterogeneity poses a challenge, as reliable tumor-specific markers are not always present.
• Development of flexible targeting platforms is needed to address multiple markers concurrently.

Purpose of the Study:

• To synthesize and evaluate a novel heterobivalent (HtBv) imaging agent.
• To assess the agent's ability to target both prostate-specific membrane antigen (PSMA) and integrin-αvβ3.
• To address tumor heterogeneity in cancer imaging through dual-targeting.

Main Methods:

• Synthesis of heterobivalent (HtBv) agents functionalized with DOTA or IRDye800CW.
• Biochemical and in vitro evaluation of binding affinities to PSMA and integrin-αvβ3.
• Preliminary in vivo evaluation using xenografts overexpressing target markers.

Main Results:

• DOTA-conjugated HtBv probe 9 exhibited binding affinities to PSMA and αvβ3 comparable to monovalent compounds.
• Conformational analysis supported the model of probe 9 binding to both targets.
• IRDye800-conjugated HtBv probe 10 demonstrated target-specific binding in xenografts.

Conclusions:

• The developed heterobivalent (HtBv) agents show promise for dual-targeted imaging.
• This approach may help overcome limitations posed by tumor heterogeneity in cancer imaging.
• Potential for improved visualization of malignant cells and tissues.