title: Photobleaching-based method to individualize irradiation time during interstitial 5-aminolevulinic acid photodynamic therapy.
abstract: Interstitial photodynamic therapy (iPDT) is being investigated for the treatment of high-grade human brain malignancies. In recent clinical studies, fluorescence monitoring during iPDT of glioblastoma multiforme has revealed patient-specific accumulation of photosensitizer (aminolevulinic acid (ALA) induced protoporphyrin IX, PpIX) and its photobleaching kinetics. As photosensitizer degradation, also referred to as photobleaching, and tissue damage are caused by the same underlying processes, the photobleaching kinetics might provide a tool for real-time treatment supervision. Here, we show with computer simulations that varying optical properties have a strong influence on the irradiation time required to fully bleach the photosensitizer. We propose a method to potentially determine the time point during iPDT, when the photosensitizer within the target volume has been largely photobleached. Simulations show that it is possible to determine this time point by continuously monitoring the ratio of the fluorescence intensities at two time points during irradiation. We show that this method works for a large range of optical properties, different photobleaching rates and varying inter-fibre distances. In conclusion, the relative fluorescence method offers the potential to individualize irradiation times to consume the photosensitizer within the target tissue during iPDT.
authors.affiliation: Laser-Forschungslabor, LIFE Center, University Hospital of Munich, Marchioninistraße 23, 81377 Munich, Germany. georg.hennig@med.uni-muenchen.de
authors.forename: Georg
authors.initials: G
authors.lastname: Hennig
authors.forename: Herbert
authors.initials: H
authors.lastname: Stepp
authors.forename: Ann
authors.initials: A
authors.lastname: Johansson
mesh_terms: D000042:Absorption; D000465:Algorithms; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy; D003198:Computer Simulation; D020342:Finite Element Analysis; D005453:Fluorescence; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D038761:Photobleaching; D010778:Photochemotherapy / Q000295:instrumentation / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000627:therapeutic use; D011829:Radiation Dosage; D011874:Radiometry; D012542:Scattering, Radiation; D013997:Time Factors
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX