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Optimal Delivery Time and Distribution of Photosensitizer in Pancreatic Cancer for Photodynamic Therapy Ablation

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P Vincent

P Vincent*, B Pogue , M Nieskoski , R Xie , K Marra , Dartmouth College, Hanover, NH


SU-I-GPD-T-647 (Sunday, July 30, 2017) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose: To determine the optimal time and regional distributions of iv injected verteporfin as a photosensitizer in photodynamic therapy (PDT) for pancreatic cancer, currently in clinical trial studies.

Methods: Verteporfin (1 mg/kg) was injected into mice with As-PC1 tumor line via tail vein and sacrificed at 6 different time points (0min, 5min, 15min, 30min, 1h and 3h) post injection. Ex vivo tumor slices (2mm) were collected and fluorescently imaged (633/685nm ex/em). The slices were embedded in paraffin, and then thinly sectioned (4μm) for Masson’s Trichrome, Lectin and H&E staining. These sections were viewed at 10x magnification. Coregistration of selective fluorescent images and pathological images were performed in Matlab. Fluorescence intensity was used to quantify verteporfin distribution in tumor tissue while information on vasculature, vascular patency and collagen was obtained by calculating the percent area stained from pathological images.

Results: Fluorescence image analysis showed increased verteporfin uptake from 5min to 1h and the photosensitizer was more evenly distributed over time with the optimal delivery time within one hour, however at the longer times also tended to pool into areas of necrosis. Optimal delivery time is characterized as the time in which veterporfin uptake from vascular areas is well-distributed in tumor tissue before it gets concentrated in necrosis areas due to pressure gradient. Percent area of stained tissue from 5min and 1h slices suggests that a minority of the tumor tissue is perfused with the agent, but that the limitations were dominated by high stroma, thereby inducing high solid stress pressures.

Conclusion: Distribution of photosensitizer uptake in tumor tissue is one of the key factors that affect treatment efficacy. While tissue heterogeneity hinders even distribution of drug uptake, this work has suggested delivery time within one hour to ensure proper distribution of verteporfin in active tumor tissues instead of necrosis areas.

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