Routine experimental system for defining conditions used in photodynamic therapy and fluorescence photodetection of (non-) neoplastic epithelia.
A common method to induce enhanced short-term endogenous porphyrin synthesis and accumulation in cell is the topical, systemic application of 5-aminolevulinic acid or one of its derivatives. This circumvents the intravenous administration of photosensitizers normally used for photodynamic therapy (PDT) of fluorescence photodetection. However, in the majority of potential medical indications, optimal conditions with respect to the porphyrin precursor or its pharmaceutical formulation have not yet been found. Due to ethical restrictions and animal right directives, the number of available test objects is limited. Hence, definition and use of nonanimal test methods are needed. Tissue and organ cultures are a promising approach in replacing cost intensive animal models in early stages of drug development. In this paper, we present a tissue culture, which can among others be used routinely to answer specific questions emerging in the field of photodynamic therapy and fluorescence photodetection. This technique uses mucosae excised from sheep paranasal sinuses or pig bladder, which is cultured under controlled conditions. It allows quasiquantitative testing of different protoporphyrin IX precursors with respect to dose-response curves and pharmacokinetics, as well as the evaluation of different incubation conditions and/or different drug formulations. Furthermore, this approach, when combined with the use of electron microscopy and fluorescence-based methods, can be used to quantitatively determine the therapeutic outcome following protoporphyrin IX-mediated PDT.
Lange
N
N
Swiss Federal Institute of Technology Lausanne, Institute of Environmental Engineering, DGR-LPAS, CH-1015 Lausanne, Switzerland. norbert.lange@epfl.ch
Vaucher
L
L
Marti
A
A
Etter
A L
AL
Gerber
P
P
van Den Bergh
H
H
Jichlinski
P
P
Kucera
P
P
D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D016923:Cell Death; D046508:Culture Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008856:Microscopy, Fluorescence; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D010256:Paranasal Sinuses / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism; D012756:Sheep; D013552:Swine; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX