5-aminolevulinic-acid-hexyl-ester and Precancerous-Conditions

Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well-established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient PpIX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non-irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1 mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104 au) than in corresponding concentrations of MAL (median 35-69 au) (P < 0.01). Fluorescence intensities in the superficial (35 au) and deep dermis (32 au) were similar for HAL and MAL (P = 0.51) and lower than epidermal fluorescence intensities (P < 0.001). Significantly, higher median PpIX fluorescence intensities (64 au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48 au) (P < 0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72 au, non-UV: 70 au) (P = 0.87). In conclusion, HAL express high affinity for epidermis and sebaceous gland epithelium, and MAL for actinically damaged skin, which raises future perspectives for improved selectivity in PDT.

Topics: Administration, Topical; Aminolevulinic Acid; Animals; Biological Availability; Female; Humans; Mice; Mice, Hairless; Microscopy, Fluorescence; Models, Animal; Photochemotherapy; Photosensitizing Agents; Porphyrins; Precancerous Conditions; Protoporphyrins; Skin; Skin Neoplasms; Tissue Distribution; Ultraviolet Rays

We aimed to determine the feasibility of obtaining selective fluorescence of precancerous/cancerous lesions in the colon with a new fluorescence video endoscope system in combination with the selective photosensitizer precursor hexaminolevulinate (HAL), and to carry out a dose-finding study with evaluation of the optimal dose and application time.. 12 patients with colorectal lesions underwent sensitization with locally applied HAL enemas in two concentrations (0.8 mmol and 1.6 mmol). The examination was conducted either 30 or 60 minutes after rectal administration of the sensitizer, using a special light source capable of delivering either white or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. Corresponding endoscopic, fluorescence, and microscopic findings were compared.. Using histological findings as the gold standard, 52/53 of the premalignant/malignant lesions showed red fluorescence under the photodynamic diagnosis (PDD) examination; 38/53 were detected with white-light endoscopy. The PDD mode showed 28 % more polyps than did white-light endoscopic imaging. The greatest fluorescence intensity in precancerous lesions was found with retention for 60 minutes of 500 ml of 1.6 mmol HAL.. Administration of HAL enema induces selective lesion fluorescence and increases the lesion detection rate in patients with colorectal adenoma and early carcinoma.

Topics: Aged; Aminolevulinic Acid; Biopsy, Needle; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Early Diagnosis; Feasibility Studies; Female; Fluorescence; Humans; Immunohistochemistry; Male; Middle Aged; Photosensitizing Agents; Precancerous Conditions; Sensitivity and Specificity

Fluorescence endoscopy is a promising new method for detection and treatment of premalignant and malignant lesions. The aim of this pilot study was to investigate the feasibility of hexaminolevulinate-based photodetection of rectal adenoma and cancer, including safety, dose finding, and efficacy.. Ten patients with known rectal adenoma or cancer were sensitized by instillation of 3.2 mM of hexaminolevulinate as an enema. Fluorescence endoscopy was performed after retention of the enema for 30 to 60 minutes, followed by a rest time of up to 30 minutes before endoscopy. Biopsy specimens were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to assess the distribution of protoporphyrin IX fluorescence in different tissue layers. Adverse events were reported by direct questioning of all patients; skin photosensitivity, changes in biochemical tests of liver function, blood pressure and heart rate, and the occurrence of GI symptoms (nausea, vomiting) were recorded for 5 patients.. Hexaminolevulinate-induced fluorescence endoscopy produced selective fluorescence of all rectal adenomas with intraepithelial neoplasia. For rectal cancer, there was only weak fluorescence or none at all. No hexaminolevulinate-induced side effect was observed. In two patients, fluorescence differentiated adenomas and hyperplastic polyps.. Hexaminolevulinate-based fluorescence endoscopy (3.2 mM administered as an enema) in patients with rectal cancer and adenoma was well tolerated and produced no significant skin sensitivity or other side effects. The optimal duration of application is 30 to 45 minutes, with a rest time of 30 minutes. Selective fluorescence of adenoma with intraepithelial neoplasia suggests that hexaminolevulinate-based fluorescence endoscopy may be useful for detection of premalignant lesions.

Topics: Adenoma; Aged; Aged, 80 and over; Aminolevulinic Acid; Biopsy; Carcinoma in Situ; Cell Transformation, Neoplastic; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Dose-Response Relationship, Drug; Feasibility Studies; Female; Fluorescent Dyes; Humans; Intestinal Mucosa; Male; Microscopy, Fluorescence; Middle Aged; Precancerous Conditions; Proctoscopy; Protoporphyrins