Predicting head and neck tumor nodule responses to TLD1433 photodynamic therapy using the image-guided surgery probe
Chanda Bhandari1, Siddharth Soma1, Maxwell Quaye1
1Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA.
Abstract:
Incomplete surgical resection in head and neck cancer can lead to locoregional recurrence in >35% of patients. Approaches such as image-guided surgery (IGS) and post-operative photodynamic therapy (PDT) have been proposed to reduce recurrence rates. However, the PDT doses needed to eliminate all unresected diseases are not established. This in vitro proof-of-concept study aims to predict head and neck tumor nodule viability in vitro following PDT with TLD1433 using the IGS probe ABY-029. ABY-029 is an EGFR-specific affibody-IRDye800CW conjugate that has undergone Phase 0 evaluation studies in head and neck cancer, among others. TLD1433 is a ruthenium-based photosensitizer in a Phase II trial for non-muscle invasive bladder cancer. Here, we demonstrate that decreases in fluorescence emission of ABY-029 bound to MOC1 mouse head and neck cancer nodules in vitro can be predictive of TLD1433 PDT responses. Results show that photoactivation of TLD1433 produces reactive oxygen species (ROS) that reduce MOC1 nodule fractional viability in a manner that is inversely correlated with ABY-029 fluorescence intensity (Pearson's r = -0.9148, R2 = 0.8369, p < 0.0001). We hypothesize that this is due to ROS-mediated degradation of IRDye800CW. The findings warrant further studies using head and neck cancer nodules with heterogenous PDT responses and EGFR expression levels. If successful, the future goal would be to use ABY-029 to guide the dosimetry of intraoperative PDT of the surgical bed after IGS to eliminate all microscopic diseases, reduce recurrence rates, and prolong survival.
Insights
This study shows that fluorescence from ABY-029 can predict head and neck cancer nodule viability after photodynamic therapy (PDT) with TLD1433. This may help guide PDT to eliminate residual cancer and reduce recurrence.
Area of Science:
- Oncology
- Biomedical Engineering
- Photodynamic Therapy
Background:
- Incomplete surgical resection in head and neck cancer leads to high locoregional recurrence rates (>35%).
- Image-guided surgery (IGS) and post-operative photodynamic therapy (PDT) are potential strategies to reduce recurrence.
- Establishing precise PDT doses to eliminate microscopic residual disease remains a challenge.
Purpose of the Study:
- To investigate if ABY-029 fluorescence can predict the efficacy of TLD1433-mediated PDT on head and neck cancer nodules in vitro.
- To establish a proof-of-concept for using image-guided probes to guide PDT dosimetry.
Main Methods:
- Utilized MOC1 mouse head and neck cancer nodules in an in vitro setting.
- Administered TLD1433 (a ruthenium-based photosensitizer) and activated it with light.
- Monitored changes in ABY-029 (an EGFR-specific affibody-IRDye800CW conjugate) fluorescence intensity.
- Assessed nodule viability and correlated it with fluorescence changes.
Main Results:
- Photoactivation of TLD1433 generated reactive oxygen species (ROS), reducing nodule viability.
- A significant inverse correlation was observed between ABY-029 fluorescence intensity and MOC1 nodule fractional viability (Pearson's r = -0.9148, R² = 0.8369, p < 0.0001).
- Hypothesized that ROS-mediated degradation of IRDye800CW contributes to the observed fluorescence decrease.
Conclusions:
- Decreased ABY-029 fluorescence is a potential predictor of TLD1433 PDT response in head and neck cancer.
- This finding supports further research into using ABY-029 for intraoperative PDT guidance to improve tumor resection and patient outcomes.
- Future studies should explore heterogeneous PDT responses and EGFR expression levels in head and neck cancer models.
