5-Aminolevulinic acid-mediated photodynamic activity in patient-derived cholangiocarcinoma organoids.

Abstract

BACKGROUND:

Accurate diagnosis of the disease extension of cholangiocarcinoma (CCA) is often difficult in clinical practice. The diagnostic yield of conventional pre-operative imaging or endoscopic procedures is sometimes insufficient for the evaluation of longitudinal spreading of CCA. Here we investigated the usefulness of 5-aminolevulinic acid (5-ALA) for the pre- or intra-operative diagnosis of CCA, using patient-derived organoids.

METHODS:

Four CCA- and two adjacent tissue-derived organoids were established. After 5-ALA treatment, we assessed their photodynamic activity using fluorescence microscopy.

RESULTS:

CCA organoids established from different patients showed diverse morphology in contrast to monolayer structures of non-tumor organoids, and had the ability to form subcutaneous tumors in immunodeficient mice. CCA organoids demonstrated remarkably high photodynamic activity based on higher accumulation of protoporphyrin IX as a metabolite of 5-ALA compared to non-tumor organoids (40-71% vs. < 4%, respectively). Importantly, cancer cell-specific high photodynamic activity distinguished the organoids originated from biliary stenotic lesions from those of non-stenotic lesions in a CCA patient. The high photodynamic activity did not depend on the expression profile of heme biosynthesis genes.

CONCLUSIONS:

Distinct 5-ALA-based photodynamic activity could have diagnostic potential for the discrimination of CCA from non-tumor tissues.

• Authors: Hiroaki Fujiwara, Naminatsu Takahara, Keisuke Tateishi, Mariko Tanaka, Sachiko Kanai, Hiroyuki Kato, Takuma Nakatsuka, Keisuke Yamamoto, Hirofumi Kogure, Junichi Arita, Yousuke Nakai, Masato Kasuga, Tetsuo Ushiku, Kiyoshi Hasegawa, Kazuhiko Koike
• Journal: Surgical oncology (Surg Oncol) Vol. 35 Pg. 484-490 (Dec 2020) ISSN: 1879-3320 [Electronic] Netherlands
• PMID: 33126085 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Levulinic Acids
• Protoporphyrins
• protoporphyrin IX

Topics

• Aged
• Aged, 80 and over
• Animals
• Bile Duct Neoplasms (drug therapy, metabolism, pathology)
• Cholangiocarcinoma (drug therapy, metabolism, pathology)
• Female
• Follow-Up Studies
• Humans
• Levulinic Acids (pharmacology)
• Male
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Middle Aged
• Organoids (drug effects, metabolism, pathology)
• Photochemotherapy (methods)
• Prognosis
• Protoporphyrins (analysis, metabolism)
• Xenograft Model Antitumor Assays
• Aminolevulinic Acid