Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid

Kriegmair, M.; Baumgartner, Reinhold; Knuechel, Ruth; Steinbach, Pia; Ehsan, A.; Lumper, W.; Hofstädter, Ferdinand; Hofstetter, A.

doi:10.1016/s0090-4295(94)80167-3

Cited by 263 publications

(134 citation statements)

References 13 publications

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“…The qualities of ALA however, make a clinical application for PDD more feasible. Kriegmair et al have used this procedure to detect carcinoma in situ of the human bladder (Kriegmair et al, 1994). The present study only evaluated women with palpable tumours.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies with PDD and PDT using ALA were performed for the treatment of neural tumours (Obwegeser et al, 1998), lesions of the oral cavity (Leuing et al, 1996), endoscopical detection of bronchial lesions (Campbell et al, 1996) and detection of carcinoma in situ of the bladder during cystoscopy (Kriegmair et al, 1994). The latter reached a sensitivity of 93%.…”

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confidence: 99%

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Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Ladner

Steiner²,

Allemann³

et al. 2001

Br J Cancer

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Photodynamic diagnosis is of increasing interest for diagnosis in oncology. It is based on a more intense incorporation of a fluorescent dye in tumours compared to normal tissue. As a feasibility study we investigated the effectiveness of oral application of 5-aminolevulinic acid for photodynamic diagnosis of human primary mammary tumours. The study included 16 patients with palpable breast tumours. Aminolevulinic acid was administered at a concentration of 40 mg kg −1 bodyweight 150–420 min prior to tumourectomy. Intraoperatively blue light (405 nm) was applied to the operation site. Sections of the excised tumour and some lymph nodes were prepared and analysed with a fluorescent microscope. All primary mammary tumour tissues showed significantly higher fluorescence intensity than surrounding normal mammary tissue. Fluorescence of the mammary tumours could also be discriminated macroscopically and intraoperatively. Fluorescence intensity in nonmetastatic lymph node tissue was higher in 2 out of 3 patients than in primary tumour tissue. By photodynamic diagnosis using aminolevulinic acid we were able to reliably distinguish primary mammary tumours from normal mammary tissue microscopically and macroscopically in all our patients. We suggest that photodynamic diagnosis with aminolevulinic acid for breast tumours should be further investigated and developed for intraoperative use and may well be a simple tool for better intraoperative diagnosis and recognition of tumour margins. We hypothesize that lymph node metastasis of breast tumours will not be detectable by this method. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Ladner

Steiner²,

Allemann³

et al. 2001

Br J Cancer

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“…For reasons that are not yet completely understood, PpIX is often produced in higher amounts by malignant cells, conferring selective photodynamic damage to the tumour area. Although most researchers have taken advantage of the selective PpIX accumulation in the tumour to treat the malignancy by means of photodynamic therapy, others have used PpIX fluorescence detection as a tool for the diagnosis of disease (Kriegmair et al, 1994;Kennedy et al, 1996).…”

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confidence: 99%

Hypoxia significantly reduces aminolaevulinic acid-induced protoporphyrin IX synthesis in EMT6 cells

1999

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SummaryWe have studied the effects of hypoxia on aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) synthesis in EMT6 monolayer cultures characterized by different cell densities and proliferation rates. Specifically, after ALA incubation under hypoxic or normoxic conditions, we detected spectrofluorometrically the PpIX content of the following populations: (a) low-density exponentially growing cells; (b) high-density fed-plateau cells; and (c) high-density unfed-plateau cells. These populations were selected either for the purpose of comparison with other in vitro studies (low-density exponentially growing cells) or as representatives of tumour regions adjacent to (highdensity fed-plateau cells) and further away from (high-density unfed-plateau cells) capillaries. The amount of PpIX per cell produced by each one of these populations was higher after normoxic ALA incubation. The magnitude of the effect of hypoxia on PpIX synthesis was dependent on cell density and proliferation rate. A 42-fold decrease in PpIX fluorescence was observed for the high-density unfed-plateau cells. PpIX production by the low-density exponential cells was affected the least by ALA incubation under hypoxic conditions (1.4-fold decrease), whereas the effect on the high-density fed-plateau population was intermediate (20-fold decrease).

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“…Topically applied ALA-PDT has proven to be a successful treatment modality for non-melanoma superficial malignant skin tumours Svanberg et al, 1994). Also, human studies have been performed using orally applied ALA (Grant et al, 1993;Regula et al, 1995) and topically applied ALA (Kriegmair et al, 1994) for endoscopic PDT treatments as well as photodetection of cancer. Sufficient tissue levels of PpIX for diagnostic and treatment purposes can also be achieved by administering ALA intravenously (i.v.…”

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confidence: 99%

Kinetics and localisation of PpIX fluorescence after topical and systemic ALA application, observed in skin and skin tumours of UVB-treated mice

Veen¹,

Bruijn²,

Berg³

et al. 1996

Br J Cancer

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SummaryIn this study the kinetics and localisation of protoporphyrin IX (PpIX) fluorescence in skin and skin tumours were examined after topically (20% for 4 h) or systemically (200 mg kg-', i.p.) administered 5-aminolaevulinic acid (ALA). As a model we used hairless mice with skin lesions (actinic keratoses and squamous cell carcinoma), which were induced by daily UVB irradiation. The epidermis of the skin surrounding the tumours (T) was altered (AS); owing to the UVB irradiation, the epidermis was thicker and less elastic. Therefore, non-UVBirradiated mice were used to assess fluorescence of normal skin (NS). Light from a halogen lamp was used to excite at 500 + 20 nm and fluorescence was detected through a filter that passes light of 670 + 50 nm. Maximal fluorescence following i.p. ALA was observed 2 h post injection (p.i.) and was three times less than after topically applied ALA. Furthermore, after i.p. ALA a lower T selectively (T/NS) could be obtained than after topically applied ALA. Maximal fluorescence following topically applied ALA was achieved 6 h after the end of the 4 h application time. At that interval fluorescence of T was twice as high as directly after the application period. Furthermore, T selectivity (T/NS) after topical ALA at the interval of maximal fluorescence was higher than at the interval directly after application. With fluorescence cryomicroscopy localisation of fluorescence in the skin at the interval of maximal fluorescence was determined after both administration routes. For both cases fluorescence was mainly located in T, epidermis and hair follicles. Fluorescence in subcutis could only be observed at 2 h post i.p. ALA and at 6 h post topical ALA. No fluorescence could be observed in muscle. We conclude that, in this model and with these ALA doses, a higher fluorescence intensity and selectivity (T/NS) was achieved after topically applied ALA than after systemically administered ALA. These results make topically applied ALA more favourable for ALA-PDT of superficial skin tumours in this model. In general these results imply that by optimising the time after ALA application the efficacy and selectivity of topical ALA-PDT for skin tumours may be improved.

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Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid

Cited by 263 publications

References 13 publications

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Hypoxia significantly reduces aminolaevulinic acid-induced protoporphyrin IX synthesis in EMT6 cells

Kinetics and localisation of PpIX fluorescence after topical and systemic ALA application, observed in skin and skin tumours of UVB-treated mice

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