12 February 2018 Verteporfin heterogeneity in pancreatic adenocarcinoma and the relationship to tumor vasculature and collagen distribution
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Abstract
Photodynamic therapy (PDT) has emerged as one promising treatment regimen for several cancer types, with a clinical trial ongoing in pancreatic adenocarcinoma (PDAC). PDT treatment efficacy mainly depends on the combination of light delivery, oxygen availability and photosensitizer uptake, each of which can be limited in pancreas cancer. Therefore, increasing drug uptake in the tumor would make an important impact on treatment outcome. This study was conducted to focus on the issue with drug resistance by examining the relationship between photosensitizer verteporfin and tissue parameters such as collagen and vascular patency. Verteporfin uptake in the tumors was assessed by fluorescence imaging while collagen content and patent vessel area fraction were quantified by evaluating Masson’s Trichrome and Lectin pathology staining images. Two tumor cell lines – AsPC-1 and BxPC-3 – were modeled in nude mice to investigate the impact of different tumor microenvironments. Experimental results highlighted the correlation between vascular patency and verteporfin uptake. Collagen content was found to be an independent factor within each tumor line, but a comparison across two tumor types suggested that collagen area of greater than 10% of tumor cross section reflected a lower verteporfin uptake. It was observed that whole-slice tumor quantifications have showcased some interesting trends which could be greatly enhanced and further supported by regional analysis.
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Phuong Vincent, Phuong Vincent, Rui Xie, Rui Xie, Michael Nieskoski, Michael Nieskoski, Kayla Marra, Kayla Marra, Jason Gunn, Jason Gunn, Brian W. Pogue, Brian W. Pogue, } "Verteporfin heterogeneity in pancreatic adenocarcinoma and the relationship to tumor vasculature and collagen distribution ", Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 1047617 (12 February 2018); doi: 10.1117/12.2309291; https://doi.org/10.1117/12.2309291
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