Laser-induced fluorescence studies of normal and malignant tumour tissue of rat following intravenous injection of δ-amino levulinic acid

Johansson, Jonas; Berg, Roger; Svanberg, Katarina; Svanberg, Sune

doi:10.1002/(sici)1096-9101(1997)20:3<272::aid-lsm6>3.0.co;2-n

Cited by 27 publications

(11 citation statements)

References 29 publications

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“…Laser-induced fluorescence of endogenous PPIX was investigated in malignant and normal tissues in mice (Nilsson et al 1994), as well as in rats (Johansson et al 1997). Comparable studies have been performed in patients in connection with photodynamic therapy (PDT) of basal cell carcinomas and adjacent normal skin following topical application of 5-Ala in order to study PPIX build-up (Klinteberg et al 1999;Palsson et al 2003), as well as in various kinds of malignant, premalignant, and benign lesions in the head and neck region ; see also Andersson-Engels et al 2009 andCelli et al 2010 for review and Chapters 16 through 18 and 23 for more details).…”

Section: Cancer Diagnostics and Therapy Employing Porphyrinssupporting

confidence: 64%

Oncology applications: Brain

Butte¹,

Mamelak²,

Marcu³

2014

Fluorescence Lifetime Spectroscopy and Imaging

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Section: Cancer Diagnostics and Therapy Employing Porphyrinssupporting

confidence: 64%

Oncology applications: Brain

Butte¹,

Mamelak²,

Marcu³

2014

Fluorescence Lifetime Spectroscopy and Imaging

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“…At 4 and 6 h, tumors showed a marked increase in the fluorescence intensity at 635 nm and 705 nm relative to the pre-ALA baseline, and after correcting for autofluorescent background, the fluorescence intensity at 635 nm showed a high tumor-to-normal skin ratio, ranging from 9:1 to 15:1. A similar kind of study was done by Johansson et al [40] to investigate the kinetics and dose-dependence of ALA-induced PpIX accumulation in different organs and tissue types in rats after intravenous administration of ALA. Fluorescence spectra from tumors and normal surrounding tissue were obtained using an optical fiber-based fluorosensor at 405 nm excitation wavelength. Using the recorded fluorescence spectra and correcting for autofluorescence, they observed that a maximum PpIX build-up in tumors was achieved within 1 h after ALA administration, as compared to the surrounding muscle, which is in harmony with other reports on intravenously (i.v.)…”

Section: Detection Of Ppix In the Skin Using Surface Measurementsmentioning

confidence: 94%

Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy

Rollakanti

Kanick

Davis

et al. 2013

Photonics &Amp; Lasers in Medicine

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Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients.

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“…Topical application of ALA was used because this method of administration is common in the treatment of skin tumors and is advantageous over systemic administration because overall body sensitization is avoided and also high systemic concentrations of ALA may be slightly neurotoxic (27,28). The amount of PpIX formed in the skin was determined by means of a fluorescence spectroscopy, which is an efficient method for noninvasive tissue imaging in vivo (29,30). Considerations for dosimetry parameters such as the drug concentration and the application time are discussed on the basis of the experimental results presented.…”

Section: Introductionmentioning

confidence: 99%

Topical Application of 5-Aminolevulinic Acid and its Methylester, Hexylester and Octylester Derivatives: Considerations for Dosimetry in Mouse Skin Model¶

Juzeniene

Juzenas

Iani

et al. 2007

Photochemistry and Photobiology

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Ester derivatives of 5‐aminolevulinic acid (ALA‐esters) have been proposed as alternative drugs for ALA in photodynamic therapy. After topical application of creams containing ALA, ALA methylester (ALA‐Me), ALA hexylester (ALA‐Hex) and ALA octylester (ALA‐Oct) on mouse skin, typical fluorescence excitation and emission spectra of protoporphyrin IX (PpIX) were recorded, exhibiting a similar spectral shape for all the drugs in the range of concentrations (0.5–20%) studied. The accumulation kinetics of PpIX followed nearly a similar profile for all the drug formulations. The fluorescence of PpIX peaked at around 6–12 h of continuous cream application. Nevertheless, some differences in pharmacokinetics were noticed. For ALA cream, the highest PpIX fluorescence was achieved using 20% of ALA in an ointment. Conversely, 10% of ALA‐Me and ALA‐Hex, but not of ALA‐Oct, in the cream was more efficient (P < 0.05) than was 20%. The cream becomes rather fluid when 20% of any of these ALA‐esters is used in ointment, whereas 10% and lower concentrations of ALA‐esters do not significantly increase fluidity of the cream. The dependence of PpIX accumulation on the concentration of ALA and ALA‐ester in the applied cream followed (P < 0.002) kinetics as described by a mathematical model based on the Michaelis–Menten equation for enzymatic processes. Under the present conditions, the PpIX amount in the skin increased by around 50% by the application of ALA‐Me, ALA‐Hex or ALA‐Oct for 4–12 h as compared with ALA for the same period. Observations of the mice under exposure to blue light showed that after 8–24 h of continuous application of ALA, the whole mouse was fluorescent, whereas in the case of ALA‐Me, ALA‐Hex and ALA‐Oct the fluorescence of PpIX was located only at the area of initial cream application. The amount of the active compound in the applied cream necessary to induce 90% of the maximal amount of PpIX was determined for normal mouse skin. Optimal PpIX fluorescence can be attained using around 5% ALA, 10% ALA‐Me and 5% ALA‐Hex creams during short application times (2–4 h). Topical application of ALA‐Oct may not gain optimal PpIX accumulation for short applications (<5 h). For long application times (8–12 h), it seems that around 1% ALA, 4% ALA‐Me, 6% ALA‐Hex and 16% ALA‐Oct can give optimal PpIX fluorescence. But for long application times and high concentrations, systemic effect of ALA applied topically on relatively large areas should be considered.

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Laser-induced fluorescence studies of normal and malignant tumour tissue of rat following intravenous injection of δ-amino levulinic acid

Cited by 27 publications

References 29 publications

Oncology applications: Brain

Oncology applications: Brain

Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy

Topical Application of 5-Aminolevulinic Acid and its Methylester, Hexylester and Octylester Derivatives: Considerations for Dosimetry in Mouse Skin Model¶

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