Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine

Nakai, Yasushi; Ozawa, Toshiyuki; Mizuno, Fumiko; Onishi, Sayuri; Owari, Takuya; Hori, Syunta; Morizawa, Yosuke; Tatsumi, Yosihiro; Miyake, Makito; Tanaka, Nobumichi; Tsuruta, Daisuke; Fujimoto, Kiyohide

doi:10.1007/s00432-017-2476-5

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…This original work did demonstrate the potential of HAL-induced fluorescence for the detection of cancer cells in urine samples [70]. The Fujimoto group reported that using HAL improved the detection of bladder cancer cells in urine samples compared to 5-ALA [73]. More recently, our findings also showed that HAL-induced PpIX fluorescence was significantly high in bladder cancer cells compared to noncancer cells [71].…”

Section: -Ala-based Approachessupporting

confidence: 52%

“…Since then, the ex vivo administration of 5-ALA [67,69] and HAL [73] or the noninvasive photodynamic diagnostic of bladder cancer in urine has been evaluated in six studies, three of which were undertaken by Fujimoto's research group (Table 4).…”

Section: -Ala-based Approachesmentioning

confidence: 99%

“…Using HAL may, therefore, reduce the chance of false-positive results and increase the potential specificity of the tests. Yet, reports investigating the usefulness of HAL for the noninvasive diagnosis of bladder cancer are sparse and only three studies [70,71,73] have been published to date.Čunderlíková and colleagues examined the rate of HAL-induced PpIX production by flow cytometry in normal urinary bladder transitional epithelial cells (NBECs) from healthy volunteer urine and in the human bladder transitional carcinoma cell line (TCCSUP). This original work did demonstrate the potential of HAL-induced fluorescence for the detection of cancer cells in urine samples [70].…”

Section: -Ala-based Approachesmentioning

confidence: 99%

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Shedding Light on Bladder Cancer Diagnosis in Urine

Chan

Gleadle

et al. 2020

Diagnostics

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Blue light cystoscopy (BLC) is the most recent clinical approach in the detection and diagnosis of bladder cancer, a common type of cancer with a high rate of recurrence. Representing a significant advance over previous approaches, this photodynamic diagnostic technique uses a photosensitiser prodrug as an adjunct to white light cystoscopy to enhance the in vivo detection of malignant tissues in the bladder based on their distinctive fluorescence. Whilst it does improve detection rates, BLC remains an invasive and costly procedure. Meanwhile, a variety of noninvasive urine detection methods and related microdevices have been developed, none of which have yet entered routine clinical use due to unsatisfactory sensitivity. Following a brief description of the current approaches and their limitations, we provide here a systematic review of a newer niche research aiming to develop a noninvasive adaptation of photodynamic diagnosis. The research to date surrounding the ex situ use of photosensitiser prodrugs for urinary diagnosis of bladder cancer is also discussed.

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Section: -Ala-based Approachessupporting

confidence: 52%

Section: -Ala-based Approachesmentioning

confidence: 99%

Section: -Ala-based Approachesmentioning

confidence: 99%

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Shedding Light on Bladder Cancer Diagnosis in Urine

Chan

Gleadle

et al. 2020

Diagnostics

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“…Over the last two decades, 5-aminolevulinic acid (5-ALA) or hexaminolevulinate-induced fluorescence cystoscopy has been established with the aim of detecting flat and/or small lesions that are hardly visible under conventional cystoscopy, leading to the decreased rate of post-TURBT residual tumor and recurrence 42. Since 2014, we have investigated the feasibility and usefulness of urine-based tests taking advantage of 5-ALA-derived fluorescence 43,44. Detection modalities are based on fluorescence microscopic cytology, fluorescence spectrophotometry, and flow cytometry.…”

Section: Introduction: Clinical Issues In Urothelial Carcinoma Of Thementioning

confidence: 99%

Emerging biomarkers for the diagnosis and monitoring of urothelial carcinoma

Miyake¹,

Owari²,

Nakai³

et al. 2018

RRU

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Urothelial carcinoma (UC) arises extensively from the renal pelvis, ureter, urinary bladder, and urethra. UC represents a clinical and social challenge because of its incidence, post-treatment recurrence rate, and prognosis. Combinations of urine cytology, cystoscopy, and conventional imaging such as computed tomography are currently used for diagnosis and monitoring modalities of UC. Both the poor diagnostic accuracy of urine cytology and poor cost performance of cystoscopy and conventional imaging modalities emphasize the urgent need for advancement in clinical guidance for UC. Urine- and blood-based biomarkers for detection of UC of the bladder and upper urinary tract represent a considerable research area. Biomarkers can help to improve UC diagnosis with the aim of replacing cystoscopy and other imaging examinations in future and may enable individualizing risk stratification regarding therapy and follow-up. Over the decades, numerous studies have focused on the potential application of biomarkers for UC, including urine, circulating tumor DNA, RNAs, proteins, and extracellular vesicles. Although some biomarkers such as ImmunoCyt/uCyt+, UroVysion, NMP-22, bladder tumor antigen, CxBladder, and Xpert Bladder Cancer are currently available in clinical practice, few biomarkers achieve high sensitivity and specificity. Emerging biomarkers are continuously developed and reported in medical journals. However, there is a significant lack on following external validation using different cohorts. The positive results are needed to be confirmed by more studies with large-scale cohorts and long follow-up periods to prove the true value of novel biomarkers, followed by their adoption in clinical practice. The present paper provides an overview of the evidence based on high-impact studies regarding urine- and blood-based biomarkers and their clinical applications in bladder cancer and upper tract UC.

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“…However, the difference in PpIX fluorescence intensity between normal and cancer cells is highly variable from one cell type to another [14]. In fact, the contrast is, in some cases, insufficient to reliably discriminate between the two, especially when applying PDD principles ex vivo, at the single cell level [15,16]. To enable the development of noninvasive diagnostic methods using PDD on body fluid sediments, such as urine [17][18][19][20], practical ways to enhance the PpIX fluorescence contrast ex vivo are required [21].…”

mentioning

confidence: 99%

Probing Hexaminolevulinate Mediated PpIX Fluorescence in Cancer Cell Suspensions in the Presence of Chemical Adjuvants

Chan

Gleadle

Vasilev

et al. 2020

IJMS

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Exogenous administration of hexaminolevulinate (HAL) induces fluorescent protoporphyrin IX (PpIX) accumulation preferentially in cancer cells. However, the PpIX fluorescence intensities between noncancer and cancer cells are highly variable. The contrast between cancer and noncancer cells may be insufficient to reliably discriminate, especially at the single cell level in cancer diagnostics. This study examines the use of the chemical adjuvants dimethylsulphoxide (DMSO) or deferoxamine (DFO) to enhance the HAL induced PpIX accumulation in cancer cells. Our results showed that in some of the incubation conditions tested, the addition of DFO with HAL significantly increased PpIX 21 fluorescence of adherent monolayer cancer cells, but this was never the case for cells in suspension. Permeabilisation with DMSO did not increase PpIX fluorescence. Cell-to-cell interaction may well play an important role in the PpIX accumulation when suspended cells are treated in HAL and adjuvant chemicals.presence of intracellular PpIX. 5-ALA based PDD is used in the detection of a wide range of cancers, such as brain [5], ovarian [6], colorectal [7], breast [8] and bladder [9]. In urology, blue light cystoscopy PPD is now recommended by several guidelines around the world. Yet the underlying mechanisms responsible for the specificity of PpIX accumulation in tumour cells remains poorly understood [10]. To date, it has been attributed to the distinctive nature of cancer cells, primarily, to reduced FECH activity [11] and to the limited availability of iron in cancer cells [12,13] or to the reduced availability of nicotinamide adenine dinucleotide phosphate (NADPH) provision. However, the difference in PpIX fluorescence intensity between normal and cancer cells is highly variable from one cell type to another [14]. In fact, the contrast is, in some cases, insufficient to reliably discriminate between the two, especially when applying PDD principles ex vivo, at the single cell level [15,16]. To enable the development of noninvasive diagnostic methods using PDD on body fluid sediments, such as urine [17][18][19][20], practical ways to enhance the PpIX fluorescence contrast ex vivo are required [21]. Strategies to do so may well be different from those that are successful in vivo, simply because the cell microenvironments are drastically different in those two scenarios.

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Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine

Abstract: Spectrophotometric photodynamic detection involving extracorporeal treatment with HAL for bladder cancer cells in voided urine showed high accuracy. This bladder cancer detection method is easy and cost-effective, and has the potential for clinical use.

Cited by 16 publications

References 26 publications

Shedding Light on Bladder Cancer Diagnosis in Urine

Shedding Light on Bladder Cancer Diagnosis in Urine

Emerging biomarkers for the diagnosis and monitoring of urothelial carcinoma

Probing Hexaminolevulinate Mediated PpIX Fluorescence in Cancer Cell Suspensions in the Presence of Chemical Adjuvants

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