| Abstrakt: |
Interest in Photodynamic Therapy is increasing; however, the translation of new photosensitizers into the clinic is stalled, despite increasing numbers of drugs synthesized for this purpose. One impediment in translating these promising compounds for photodynamic therapy into clinical studies is wide variability in the reporting of in vitro efficacy, not allowing the receptor industry to identify very promising compounds. Here we propose an in vitro cell response model, based on the photodynamic threshold model published previously, to compare the quantum efficiency of different ruthenium coordination-complexes based photosensitizers. The thresholds are given in [hν cm-3] units or the number of photons absorbed by the photosensitizer per volume. Here we compare the efficacy of Ruthenium Coordination complexes published in the past 20 years as model systems for a strategy to provide wavelength and absorption coefficient independent efficacy reports for in vitro PDT studies. Equation (1), Presents a calculation of the threshold value whereby ε(λ) [µM-1 cm-1] presents the wavelength-dependent molar absorption coefficient, [PS] LD50 the photosensitizer concentration when the LD50 is reached for a constant radiant exposure H [J cm-2]. hc/λ is the conversion factor from [J cm-2] to [hν cm-3]. ▪ By calculating a photosensitizer's quantum efficiency to reach a predetermined endpoint, here to induce a 50% reduction in cell survival, the LD50 results in a wavelength and molar extinction coefficient independent measure. Additionally, the threshold value contains the responsivity of a cell line to PDT The available studies comprised reports for ALA-induced PPIX, using PDT activation wavelengths between 450 nm and 700 nm, either a laser wavelength or broadband light sources, applied to different cell lines. For TLD1433 data for ten different cell lines, were available with excitation wavelengths ranging from 525 nm to 625 nm. For ALA induced PPIX mediated PDT in vitro the average photodynamic LD 50 threshold was 5.08 1016 ± 7.04 1016 [hν cm−3] and for TLD1433 9.28 1016 ± 1.08 1017 [hν cm−3]. Threshold values of compounds are in Table. The complete table will be presented during the conference presentation [ABSTRACT FROM AUTHOR] |
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