Tissue distribution and penetration of 5-ALA induced fluorescence in an amelanotic melanoma after topical application.
BACKGROUND
Photodynamic therapy (PDT) following topical application of 5-aminolevulinic acid (ALA) is increasingly employed for several types of malignancies. However, data with respect to tissue penetration and distribution of ALA-induced porphyrins after topical application are scarce. Therefore, it was our aim to study tissue distribution and the penetration potency of topically applied ALA.


METHODS
We used Syrian golden hamsters implanted with the amelanotic melanoma A-Mel-3 growing in a transparent dorsal skinfold chamber. ALA was topically applied in aqueous solution at a concentration of 3% for 4 hours. The fluorescence pattern was quantified by fluorescence microscopy and digital image analysis from cryosections and given as percentage of a reference standard in medians (25%, 75% quartiles).


RESULTS
Fluorescence intensities in tumors were 90.8% (56.2%, 115.2% of a reference standard, p < 0.01 vs. normal tissue) significantly exceeding normal surrounding host tissue yielding fluorescence intensities of 12.1% (9.1%, 16.1%). The tumor selectivity, that is the ratio of fluorescence intensities between tumor and normal tissue, was 7.3 (6.1, 9.1). For superficial tumors with a thickness of approximately 1 mm no fluorescence gradients after topical application of ALA could be observed.


CONCLUSIONS
In superficial cancerous lesions the fluorescence distribution of ALA induced porphyrins is tumor selective without significant fluorescence gradients throughout the tumor. Thus, by optimising the treatment modalities for topical ALA-PDT an enhanced efficacy and selectivity will be reached.
Pahernik
S
S
Institute for Surgical Research, Marchioninistrasse 15, University of Munich, 81377 Munich, Germany. Pahernik@Urologie.Klinik.Uni-Mainz.de
Langer
S
S
Botzlar
A
A
Dellian
M
M
Goetz
A E
AE
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D006224:Cricetinae; D008297:Male; D018328:Melanoma, Amelanotic / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000378:metabolism; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX