5-Aminolevulinic-acid-mediated Photodynamic Diagnosis Enhances the Detection of Peritoneal Metastases in Biliary Tract Cancer in Mice

Kubota, Toshihiro; Noji, Takehiro; Ebihara, Yuma; Hontani, Koji; Ono, Masato; Kuwabara, Shota; Nakamura, Tõru; Tsuchikawa, Takahiro; Okamura, Keisuke; Ishizuka, Masahiro; Hirano, Satoshi

doi:10.21873/invivo.11145

Cited by 8 publications

(7 citation statements)

References 25 publications

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“…Previous studies incorporating in vivo fluorescence endoscopy for bladder cancer detection in rats used xenograft or orthotopic tumor models [ 27 , 28 ]. Unlike these models, BBN causes tumorigenesis without surgery.…”

Section: Discussionmentioning

confidence: 99%

Fluorescence-Based Microendoscopic Sensing System for Minimally Invasive In Vivo Bladder Cancer Diagnosis

Lee

Cho

et al. 2022

Biosensors

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Bladder cancer is commonly diagnosed by evaluating the tissue morphology through cystoscopy, and tumor resection is used as the primary treatment approach. However, these methods are limited by lesion site specificity and resection margin, and can thereby fail to detect cancer lesions at early stages. Nevertheless, rapid diagnosis without biopsy may be possible through fluorescence sensing. Herein, we describe a minimally invasive imaging system capable of sensing even small tumors through a 1.2 mm diameter flexible fiber bundle microprobe. We demonstrate that this new device can be used for the early diagnosis of bladder cancer in rats. Bladder cancer was induced in rats using the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), and a togglable filter capable of PpIX fluorescence sensing was installed in the microendoscopic system. Following 5-aminolevulinic acid administration, tissue in the early stages of bladder cancer was successfully identified with fluorescence detection and confirmed with hematoxylin/eosin and ferrochelatase staining. Although the time required for BBN to induce bladder cancer varied between 3 and 4 weeks among the rats, the microendoscopic system allowed the minimally invasive follow-up on cancer development.

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Section: Discussionmentioning

confidence: 99%

Fluorescence-Based Microendoscopic Sensing System for Minimally Invasive In Vivo Bladder Cancer Diagnosis

Lee

Cho

et al. 2022

Biosensors

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“…Similarly, clear fluorescence was observed only within a specific timeframe following 5-ALA administration. In previous studies, the optimal time to evaluate the fluorescence of 5-ALA in PDD was indicated to be 1–4 h [ 51 , 53 ]. Although these studies involved different cell lines and routes of drug administration, they do not contradict our results.…”

Section: Discussionmentioning

confidence: 99%

5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models

et al. 2021

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Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.

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“… 19 Here, nude mice with subcutaneous human pancreatic adenocarcinoma BxPC3 tumors were used for imaging, which was performed 6 h after intraperitoneal injection of ALA (

). 20 This extended time point was chosen to allow PpIX production throughout the mouse body and subsequent accumulation in the tumor. Even though two of the five specimens analyzed in this study showed sufficient contrast naturally between tumor and normal tissue, tissues were palpated before imaging to further amplify hypoxia transiently [ Fig.…”

Section: Resultsmentioning

confidence: 99%

Protoporphyrin IX delayed fluorescence imaging: a modality for hypoxia-based surgical guidance

2022

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. Significance Hypoxia imaging for surgical guidance has never been possible, yet it is well known that most tumors have microregional chronic and/or cycling hypoxia present as well as chaotic blood flow. The ability to image oxygen partial pressure ( ) is therefore a unique control of tissue metabolism and can be used in a range of disease applications to understand the complex biochemistry of oxygen supply and consumption. Aim Delayed fluorescence (DF) from the endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique reporter of the local oxygen partial pressure in tissue. PpIX is endogenously synthesized by mitochondria in most tissues, and the particular property of DF emission is directly related to low microenvironmental oxygen concentration. Here, it is shown that PpIX has a unique emission in hypoxic tumor tissue regions, which is measured as a DF signal in the red to near-infrared spectrum. Approach A time-gated imaging system was used for PpIX DF for wide field direct mapping of changes. Acquiring both prompt and DF in a rapid sequential cycle allowed for imaging oxygenation in a way that was insensitive to the PpIX concentration. By choosing adequate parameters, the video rate acquisition of images could be achieved, providing real-time tissue metabolic information. Results In this report, we show the first demonstration of imaging hypoxia signals from PpIX in a pancreatic cancer model, exhibiting contrast relative to surrounding normal oxygenated tissues. Additionally, tissue palpation amplifies the signal and provides intuitive temporal contrast based upon neoangiogenic blood flow differences. Conclusions PpIX DF provides a mechanism for tumor contrast that could easily be translated to human use as an intrinsic contrast mechanism for oncologic surgical guidance.

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5-Aminolevulinic-acid-mediated Photodynamic Diagnosis Enhances the Detection of Peritoneal Metastases in Biliary Tract Cancer in Mice

Cited by 8 publications

References 25 publications

Fluorescence-Based Microendoscopic Sensing System for Minimally Invasive In Vivo Bladder Cancer Diagnosis

Fluorescence-Based Microendoscopic Sensing System for Minimally Invasive In Vivo Bladder Cancer Diagnosis

5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models

Protoporphyrin IX delayed fluorescence imaging: a modality for hypoxia-based surgical guidance

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