Improving the use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for the gastrointestinal tract by esterification - An in vitro study

Krieg, R. C. and Uihlein, D. and Murthum, T. and Endlicher, E. and Hausmann, F. and Messmann, H. and Knuechel, Ruth (2002) Improving the use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for the gastrointestinal tract by esterification - An in vitro study. CELLULAR AND MOLECULAR BIOLOGY, 48 (8). pp. 917-923. ISSN 0145-5680

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Abstract

Possible approaches to improve the diagnostic and therapeutic effects of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) are the esterification of ALA for enhanced uptake and the choice of wavelength for irradiation. The human colonic cell lines HT29 [G2] and CCD 18 (fibroblasts) were incubated with 0.6 mM ALA, ALA-hexylester or -benzylester respectively, and for further assays with hypotaurine, in addition. PPIX-accumulation was analyzed by flow cytometry and fluorescence spectroscopy. PPIX formation kinetics were continuously recorded. Incubated cells were irradiated with an incoherent light source lambda=400-700 nm or lambda=590-700 nm, respectively. After PDT treatment, clonogenicity assays were performed to determine cell viability. Esterification leads to increased PPIX-accumulation, decreased time for production of detectable amounts of PPIX as well as increased response to PDT. Tumor specificity is always maintained or exceeds values for ALA alone. ALA enters the cells via beta transporter whereas esters by passive diffusion. Altering irradiation wavelengths showed the independence of wavelength rather than light dose. Results emphasize the role of heme metabolism for generating tumor specificity rather than the process of ALA-uptake, an important detail for future clinical application.

Item Type: Article
Uncontrolled Keywords: PHOTODYNAMIC THERAPY; ADENOCARCINOMA CELLS; AMINOLEVULINIC-ACID; BETA TRANSPORTERS; ESTERS; COLON; SENSITIZATION; ACCUMULATION; DERIVATIVES; CARCINOMA; photodynamic diagnosis; PDD; photodynamic therapy; PDT; ALA; PPIX; in vitro; gastrointestinal neoplasia
Subjects: 500 Science > 540 Chemistry & allied sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Pathologie
Chemistry and Pharmacy > Institut für Anorganische Chemie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 28 Sep 2021 09:55
Last Modified: 28 Sep 2021 09:55
URI: https://pred.uni-regensburg.de/id/eprint/39592

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