Langer, Stefan and Abels, Christoph and Botzlar, Andreas and Pahernik, Sascha and Rick, Kai and Szeimies, Rolf-Markus and Goetz, Alwin E. (1999) Active and higher intracellular uptake of 5-aminolevulinic acid in tumors may be inhibited by glycine. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 112 (5). pp. 723-728. ISSN 0022-202X,
Full text not available from this repository. (Request a copy)Abstract
Topical 5-aminolevulinic acid is used for the fluorescence-based diagnosis and photodynamic treatment of superficial precancerous and cancerous lesions of the skin. Thus, we investigated the kinetics of 5-aminolevulinic acid-induced fluorescence and the mechanisms responsible for the selective formation of porphyrins in tumors in vivo. Using amelanotic melanomas (A-Mel-3) grown in dorsal skinfold chambers of Syrian golden hamsters fluorescence kinetics were measured up to 24 h after topical application of 5-aminolevulinic acid (1%, 3%, or 10%) for 1 h, 4 h, or 8 h by intravital microscopy (n = 54), Maximal fluorescence intensity in tumors after 1 h application (3% Ei-aminolevulinic acid) occurred 150 min and after 4 h application (3% 5-aminolevulinic acid) directly thereafter. Increasing either concentration of 5-aminolevulinic acid or application time did not yield a higher fluorescence intensity, The selectivity of the fluorescence in tumors decreased with increasing application time, Fluorescence spectra indicated the formation of protoporphyrin IX (3% 5-aminolevulinic acid, 4 h; n = 3), The simultaneous application of 5-aminolevulinic acid (3%, 4 h) and glycine (20 mu M or 200 mu M; n = 10) reduced fluorescence in tumor and surrounding host tissue significantly, In contrast, neither decreasing iron concentration by desferrioxamine (1% and 3%; n = 10) nor inducing tetrapyrrole accumulation using 1,10-phenanthroline (7.5 mM; n = 5) increased fluorescence in tumors. The saturation and faster increase of fluorescence in the tumor together with a reduction of fluorescence by the application of glycine suggests an active and higher intracellular uptake of 5-aminolevulinic acid in tumor as compared with the surrounding tissue. Shorter application (1 h) yields a better contrast between tumor and surrounding tissue for fluorescence diagnosis. The additional topical application of modifiers of the heme biosynthesis, desferrioxamine or 1,10-phenanthroline, however, is unlikely to enhance the efficacy of topical 5-aminolevulinic acid-photodynamic therapy at least in our model.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DELTA-AMINOLEVULINIC-ACID; TOPICAL PHOTODYNAMIC THERAPY; INDUCED PROTOPORPHYRIN-IX; TERM FOLLOW-UP; AMELANOTIC MELANOMA; SKIN TUMORS; IN-VIVO; ENDOGENOUS PROTOPORPHYRIN; SACCHAROMYCES-CEREVISIAE; SOLAR KERATOSES; amelanotic melanoma; fluorescence kinetics; protoporphyrin; topical application |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Oct 2022 09:53 |
| Last Modified: | 25 Oct 2022 09:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48285 |
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