title: 5-aminolevulinic acid for quantitative seek-and-treat of high-grade dysplasia in Barrett's esophagus cellular models.
abstract: High-grade dysplasia (HGD) in Barrett’s esophagus (BE) poses increased risk for developing esophageal adenocarcinoma. To date, early detection and treatment of HGD regions are still challenging due to the sampling error from tissue biopsy and relocation error during the treatment after histopathological analysis. In this study, CP-A (metaplasia) and CP-B (HGD) cell lines were used to investigate the “seek-and-treat” potential using 5-aminolevulinic acid-induced protoporphyrin IX (PpIX). The photodynamic therapy photosensitizer then provides both a phototoxic effect and additional image contrast for automatic detection and real-time laser treatment. Complementary to our studies on automatic classification, this work focused on characterizing subcellular irradiation and the potential phototoxicity on both metaplasia and HGD. The treatment results showed that the HGD cells are less viable than metaplastic cells due to more PpIX production at earlier times. Also, due to mitochondrial localization of PpIX, a better killing effect was achieved by involving mitochondria or whole cells compared with just nucleus irradiation in the detected region. With the additional toxicity given by PpIX and potential morphological/textural differences for pattern recognition, this cellular platform serves as a platform to further investigate real-time “seek-and-treat” strategies in three-dimensional models for improving early detection and treatment of BE.
authors: McMaster University, School of Biomedical Engineering, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: Shu-Chi Allison
authors: SC
authors: Yeh
authors: McMaster University, Department of Engineering Physics, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: Celine S N
authors: CS
authors: Ling
authors: Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 Canada.
authors: David W
authors: DW
authors: Andrews
authors: McMaster University, Department of Medical Physics and Applied Radiation Sciences, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: Michael S
authors: MS
authors: Patterson
authors: McMaster University, Department of Medical Physics and Applied Radiation Sciences, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: Kevin R
authors: KR
authors: Diamond
authors: McMaster University, Department of Medical Physics and Applied Radiation Sciences, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: Joseph E
authors: JE
authors: Hayward
authors: McMaster University, Division of Gastroenterology, Department of Medicine, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: David
authors: D
authors: Armstrong
authors: McMaster University, School of Biomedical Engineering, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 CanadabMcMaster University, Department of Engineering Physics, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 Canada.
authors: Qiyin
authors: Q
authors: Fang
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008954:Models, Biological; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX