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Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using
Jaeyul Lee1,2, Sangyeob Han1,3, Til Bahadur Thapa Magar4
1School of Electronic and Electrical Engineering, College of IT Engineering, Kyungpook National University, Daegu 41566, Republic of Korea.
Abstract:
To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.
Insights
This study developed a waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system to monitor vascular changes during photodynamic therapy (PDT) in pancreatic cancer. WGS-PAM revealed significant vascular reduction and anti-vascularization effects post-PDT.
Area of Science:
- Biomedical Optics
- Cancer Research
- Medical Imaging
Background:
- Photodynamic therapy (PDT) shows promise for cancer treatment, but its effects on tumor vasculature require detailed investigation.
- Previous studies have limited attention to dynamic vascular changes during PDT in orthotopic pancreatic cancer models.
- High-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) offers potential for real-time monitoring of these vascular alterations.
Purpose of the Study:
- To develop and implement a novel waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system for in vivo monitoring of vascular dynamics during PDT.
- To investigate the anti-vascularization effects of Chlorin e6 (Ce6)-mediated PDT in an orthotopic pancreatic cancer mouse model.
- To analyze the impact of PDT on microvasculature, apoptosis, necrosis, and VEGF expression in pancreatic cancer.
Main Methods:
- Development of a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system.
- In vivo monitoring of microvasculature in an orthotopic pancreatic cancer mouse model using WGS-PAM at 30-minute intervals for 3 hours post-PDT treatment with Ce6 and 660 nm light irradiation.
- Analysis of PAM images for vascular intensity and density changes, complemented by fluorescent imaging and assessment of apoptotic/necrotic markers and VEGF expression in cancer cell lines.
Main Results:
- The WGS-PAM system successfully visualized microvasculature changes in a 40 mm² area over 3 hours post-PDT.
- A significant decline in vascular intensity (24.5%) and vascular density (32.4%) was observed at 3 hours post-PDT.
- Ce6-PDT demonstrated an anti-vascularization effect, increased apoptotic and necrotic markers, and decreased VEGF expression in pancreatic cancer cells.
Conclusions:
- The developed WGS-PAM system provides high-resolution, wide-field imaging for investigating dynamic angiographic changes during PDT.
- WGS-PAM is a valuable tool for understanding the anti-vascularization mechanisms of PDT in pancreatic cancer.
- This approach holds potential for monitoring PDT efficacy and guiding treatment strategies.
