Optimization of a Protease Activated Probe for Optical Surgical Navigation
Joshua J Yim, Martina Tholen, Alwin Klaassen1
1Intuitive Surgical Inc. , 1020 Kifer Road , Sunnyvale , California 94086 , United States.
Molecular Pharmaceutics
|November 28, 2017
Summary
A new molecularly targeted optical contrast agent, 6QC-ICG, uses indocyanine green (ICG) dye for improved tumor visualization. This probe enhances surgical precision by optimizing signal detection with clinical imaging systems, enabling earlier detection of small lesions.
Area of Science:
- Biomedical imaging
- Optical contrast agents
- Surgical navigation
Background:
- Molecularly targeted optical contrast agents can improve surgical precision by visualizing specific molecular markers.
- Protease-activated fluorescent probes highlight tumor microenvironments but often use dyes mismatched to clinical imaging systems.
- Clinical camera systems are typically optimized for indocyanine green (ICG) detection.
Purpose of the Study:
- To optimize a small molecule fluorescently quenched protease substrate probe (6QC-ICG) using indocyanine green (ICG) as the reporter dye.
- To evaluate the probe's dosing and kinetic parameters in tumor-bearing mice for optimal signal detection.
- To assess the probe's performance with clinical imaging systems for surgical navigation.
Main Methods:
- Optimization of a small molecule fluorescently quenched protease substrate probe (6QC-ICG) utilizing the indocyanine green (ICG) dye.
- Evaluation of dosing and kinetic parameters in tumor-bearing mice.
- Comparison of ICG-labeled probe signal intensity with a similar probe using a spectrally shifted dye on an FDA-approved surgical imaging system (da Vinci Si with Firefly).
Main Results:
- Optimal tumor-to-background signals were observed at 90 minutes with a 2.3 mg/kg dose of 6QC-ICG.
- The fluorescence intensity of the probe signal did not linearly scale with dose, highlighting the need for detailed dosing studies.
- The ICG-labeled probe (6QC-ICG) generated significantly higher signals compared to a spectrally similar dye probe, enabling detection of small lesions (<5 mm).
Conclusions:
- The 6QC-ICG probe is highly sensitive and performs optimally with clinical imaging systems.
- The probe's ability to generate strong signals with FDA-approved systems enhances its potential for optical surgical navigation.
- Optimized dye selection and dosing are crucial for maximizing the efficacy of molecularly targeted optical contrast agents in surgery.
