No abstract

In air and in tissue optical phantoms the fluence rate distribution of the device was highly homogeneous. The observed inter-subject and intra-subject variations in fluence rate in healthy volunteers originated from differences in optical properties and nasopharyngeal geometry. Light delivery based on a single tissue surface measurement will not be adequate. In situ dosimetric measurements are required to determine the light fluence delivered to a geometrically complex site such as the nasopharynx. These observations should be taken in consideration when developing light applicators for PDT of the nasopharynx and other non-uniform surfaces.

In the present study, photodynamic activity of a novel photosensitizer (PS), Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.) injection of BLC 1010 into the CAM vasculature, the applicability of this drug for photodynamic therapy (PDT) was assessed in terms of fluorescence pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity. The influence of different PDT parameters including drug and light doses on the photodynamic activity of BLC 1010 has been investigated. It was found that, irrespective of drug dose, an identical continuous decrease in fluorescence contrast between the drug inside and outside the blood vessels was observed. The optimal treatment conditions leading to desired vascular damage were obtained by varying drug and light doses. Indeed, observable damage was achieved when irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v. injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when irradiation with light doses of more than 10 J/cm(2) was performed 1 min after injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large blood vessels. It has been demonstrated that it is possible to obtain the desired vascular occlusion and stasis with BLC 1010 for different combinations of drug and/or light doses.

The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan absorption.

For most Photodynamic Therapy (PDT) applications a diffuse, broad and uniform source of irradiation is needed to obtain the most effective and consistent treatment. Since many treatments are within the patient's body, an effective. compact fiber optic delivery system is needed for the activation of the photosensitizer drug at the site of the tissue to be treated. High Numerical Aperture (NA) optical fibers have benefits for PDT treatments but possibly even more so for PDT diagnostic applications. These are summarized and new optical fibers with high and ultra high NAs are described. Properties of these fibers are presented as well as advantages they have over other fibers for delivering light in various PDT applications. Silica fibers with enhanced. effective NAs approaching 0.6 are described.