Advancing Molecular-Guided Surgery through probe development and testing in a moderate cost evaluation pipeline

Area of Science:

• Oncology
• Surgical Navigation
• Molecular Imaging

Background:

• Molecular guided surgery offers transformative potential, especially in neurosurgery where tumor margins are unclear.
• Significant financial barriers hinder the clinical advancement of imaging agents due to high upfront costs and limited revenue models.
• Current development paradigms for biological therapeutics are not viable for imaging contrast agents.

Purpose of the Study:

• To propose and test a novel, cost-effective pathway for developing molecular imaging agents for fluorescence-guided surgery (FGS).
• To overcome financial barriers by utilizing the chemical agent approval pathway and targeting initial Phase 0 trials funded by grants.
• To accelerate the de-risking of the development pipeline and facilitate human testing of FGS reporters.

Main Methods:

• Development of small molecular biologicals tagged with a fluorescent reporter (IRDye 800CW).
• Utilizing peptide synthesis for epidermal growth factor receptor (EGFR)-binding Affibody molecules.
• Leveraging established GMP production, toxicity testing, and early-phase clinical trial expertise.

Main Results:

• The proposed pathway enables initial startup phases to be fully funded by a single NIH grant.
• Fast-tracked trials can be completed to de-risk the development pipeline.
• This approach facilitates the advancement of FGS reporters into human testing more efficiently.

Conclusions:

• The proposed pathway offers a stable and productive method for advancing fluorescence-guided surgery reporters.
• This strategy mitigates the high cost and risk associated with developing isolated molecular agents.
• The successful testing of EGFR-binding Affibody molecules conjugated to IRDye 800CW demonstrates the viability of this approach.