Performance of a dedicated light delivery and dosimetry device for photodynamic therapy of nasopharyngeal carcinoma: phantom and volunteer experiments.

UNLABELLED: The objective of this study was to develop a light delivery and measurement device for photodynamic therapy (PDT) in the nasopharyngeal cavity, which achieves a homogeneous and reproducible fluence rate distribution to a target area and provides proper shielding of predefined risk areas. MATERIALS AND METHODS: A flexible silicone applicator was developed, incorporating light delivery and dosimetry fibers. The applicator can be inserted through the mouth and fixed in the nasopharyngeal cavity. Tissue optical phantoms were prepared on the basis of optical properties measured in vivo using diffuse reflectance spectroscopy (DRS). The fluence rate over the length of the applicator surface was measured in air, in tissue optical phantoms and in five healthy volunteers. RESULTS: The fluence rate distribution over the applicator surface in air and tissue optical phantom was found to be more homogeneous (SD/mean 3.8% and 18.3%, respectively) than the fluence rate distribution in five volunteers (SD/mean ranging from 19% up to 52%). The maximum observed fluence rate build-up in the nasopharynx varied between subjects and ranged from a factor of 4.1-6.9. Shielding of the risk area such as the soft palate and tongue was effective. CONCLUSIONS: 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 vivo fluence rate measurements during Foscan-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator.

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.

Photothrombic activity of m-THPC-loaded liposomal formulations: pre-clinical assessment on chick chorioallantoic membrane model.

The objective of this study was to evaluate the ability of meso-tetra(hydroxyphenyl)chlorin (m-THPC) encapsulated into liposomal formulations to occlude neovascularization. Two m-THPC formulations including conventional or plain liposomes (Foslip) based on dipalmitoylphosphatidylcholine (DPPC) and the corresponding long-circulating poly(ethylene glycol) (PEG)-modified liposomes (PEGylated liposomes: Fospeg) were evaluated as delivery systems. Using the chick chorioallantoic membrane (CAM) as in vivo model, the fluorescence pharmacokinetic behaviour of encapsulated m-THPC reflecting the rate of the extravasation of the dye from the CAM vasculature and its photothrombic effectiveness were determined. This study was focused on the influence of the drug and/or light doses on the mean retention time of m-THPC within the CAM blood vessels after intravenous injection, and its photothrombic efficacy. Irrespective of the formulations tested and the drug doses injected, similar fluorescence pharmacokinetic profiles were obtained. The fluorescence contrast reached a steady state 30 s after injection. Constant positive values of the fluorescence contrast suggest that m-THPC is confined into the intravascular compartment during the experimental time (500 s). However, the photodynamic therapy assays showed that Foslip appears to be less potent than Fospeg in terms of photothrombic activities on the CAM model. For instance, the light dose necessary to induce the desired vascular damage with Foslip was twice (100 J/cm2) higher than with Fospeg (50 J/cm2). It can be inferred that this pre-clinical study showed that the formulation based on PEGylated liposomes technology offers a suitable delivery system for the treatment of choroidal neovascularization associated with age-related macular degeneration.

Preclinical evaluation of a novel water-soluble chlorin E6 derivative (BLC 1010) as photosensitizer for the closure of the neovessels.

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.

Shivering following cardiac surgery: predictive factors, consequences, and characteristics.

BACKGROUND: Shivering is common after cardiac surgery and may evoke harmful hemodynamic changes. Neither those changes nor factors increasing probability of shivering are well defined. OBJECTIVES: (1) To identify factors linked with risk of shivering by comparing age, weight, body surface area, gender, intraoperative details, anesthetics, postoperative temperatures, hemodynamics, and therapeutics in shivering vs nonshivering patients. (2) To describe temperatures, hemodynamics, therapeutics, myocardial oxygen consumption correlates (rate-pressure product, heart rate, systemic vascular resistance) in shivering and nonshivering groups, and shivering and nonshivering periods. (3) To characterize the electromyogram to determine whether the tremor is cold-induced. METHODS: A descriptive design with a time series component was used to study a convenience sample of 10 shivering and 10 nonshivering adults for 4 hours during early recovery from cardiac surgery. Pulmonary artery and skin (facial, calf, trunk) temperature were measured every 60 seconds; heart rate and arterial pressure, every 15 minutes; cardiac output, 3 times. Electromyogram was recorded intermittently. Medications and treatments were noted. RESULTS: Lower skin temperature was significantly related to shivering risk. Heart rate was significantly higher initially in shiverers and remained higher by 13.6 beats per minute. Significantly more nitroprusside was used to control arterial pressure before than after shivering. No significant differences were noted between groups in core temperature, age, weight, body surface area, anesthesia type, intraoperative temperature; or surgery, circulatory bypass, or cardiac cross-clamp duration. The electromyogram pattern during shivering was typical of that produced by cold. CONCLUSIONS: These results suggest that true shivering occurs after cardiac surgery. Skin, but not core, temperature and elevated heart rate predict shivering. Shivering may be more likely in hemodynamically unstable patients.

Relative changes in oxyhemoglobin, deoxyhemoglobin and intracranial blood volume during surfactant replacement therapy in infants with respiratory distress syndrome.

Oxy-, deoxyhemoglobin and total blood volume were studied by near-infrared spectroscopy (NIRS) during surfactant replacement therapy. These parameters were compared with parameters watched during conventional noninvasive monitoring (pulseoximetry, transcutaneous pO2 and pCO2, heart rate). Seven premature infants (28 +/- 3 weeks of gestation, 940 g birth weight) were given surfactant intratracheally. Immediately after surfactant administration, oxyhemoglobin decreased, deoxyhemoglobin and total blood volume increased. The prior status was re-established after 60-220 s and then oxyhemoglobin increased to a very stable maximum. NIRS allows continuous bedside noninvasive monitoring of all parameters.