Photodynamic and Nail Penetration Enhancing Effects of Novel Multifunctional Photosensitizers Designed for The Treatment of Onychomycosis.

Novel multifunctional photosensitizers (MFPSs), 5,10,15-tris(4-N-methylpyridinium)-20-(4-phenylthio)-[21H,23H]-porphine trichloride (PORTH) and 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE), derived from 5,10,15-Tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and designed for treatment of onychomycosis were characterized and their functionality evaluated. MFPSs should function as nail penetration enhancer and as photosensitizer for photodynamic treatment (PDT) of onychomycosis. Spectrophotometry was used to characterize MFPSs with and without 532 nm continuous-wave 5 mW cm(-2) laser light (± argon/mannitol/NaN3 ). Nail penetration enhancement was screened (pH 5, pH 8) using water uptake in nails and fluorescence microscopy. PDT efficacy was tested (pH 5, ± argon/mannitol/NaN3 ) in vitro with Trichophyton mentagrophytus microconida (532 nm, 5 mW cm(-2) ). A light-dependent absorbance decrease and fluorescence increase were found, PORTH being less photostable. Argon and mannitol increased PORTH and PORTHE photostability; NaN3 had no effect. PDT (0.6 J cm(-2) , 2 µm) showed 4.6 log kill for PORTH, 4.4 for Sylsens B and 3.2 for PORTHE (4.1 for 10 µm). Argon increased PORTHE, but decreased PORTH PDT efficacy; NaN3 increased PDT effect of both MFPSs whereas mannitol increased PDT effect of PORTHE only. Similar penetration enhancement effects were observed for PORTH (pH 5 and 8) and PORTHE (pH 8). PORTHE is more photostable, effective under low oxygen conditions and thus realistic candidate for onychomycosis PDT.

MR and CT based treatment planning for mTHPC mediated interstitial photodynamic therapy of head and neck cancer: description of the method.

BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy is a potentially important tool in the management of voluminous or deep-seated recurrent head and neck cancers. STUDY DESIGN/METHODS: The described treatment algorithm in this manuscript consists of the treatment simulation, implantation of light sources, verification, modification of the treatment plan if necessary, and illumination. The tumor is delineated on imaging sections (CT, MRI, and/or PET/CT) and the treatment is simulated by virtually introducing light sources to the tumor volume on specially modified brachytherapy software. This enables us to determine if the treatment is technically feasible, and information about approximate number and location of light sources necessary. Following implantation of catheters in which the light sources will be introduced, CT or MR scan is performed to verify the actual location of the implanted catheters. The verification-CT is imported to the software and co-registered with pre-treatment images to observe the deviations from the simulation. The simulation is run again with the actual position of the light sources to determine if any additional light sources are necessary and adaptation of the source length in order to cover the tumor volume (modification). Thereafter the tumor is illuminated. RESULTS: This method has the potential to help with identifying iPDT feasible patients by simulating before the actual treatment. The suboptimal placement of light sources can be identified and corrected. The simulations were documented and saved for subsequent evaluation of the technique. CONCLUSION: The proposed technique can help standardize and document iPDT.

Clinical feasibility of monitoring m-THPC mediated photodynamic therapy by means of fluorescence differential path-length spectroscopy.

The objective quantitative monitoring of light, oxygen, and photosensitizer is challenging in clinical photodynamic therapy settings. We have previously developed fluorescence differential path-length spectroscopy (FDPS), a technique that utilizes reflectance spectroscopy to monitor microvascular oxygen saturation, blood volume fraction, and vessel diameter, and fluorescence spectroscopy to monitor photosensitizer concentration. In this paper the clinical feasibility of the technique is tested on eight healthy volunteers and on three patients undergoing PDT of oral cavity cancers. Model-based analysis of the measured spectra provide quantitative tissue parameters that are corrected for background tissue absorption, autofluorescence, and the transmission of the optical system; this method allows comparison of intra- and inter-subject parameters. The FDPS correctly estimated the absence of m-THPC in volunteers and detected photobleaching in the areas receiving treatment light in patients undergoing PDT treatment. This study demonstrates the feasibility of monitoring clinical photodynamic therapy treatments using optical spectroscopy.