Determination of threshold dose of photodynamic therapy to measure superficial necrosis.

BACKGROUND DATA: Photodynamic therapy (PDT) involves the photoinduction of cytotoxicity using a photosensitizer agent, a light source of the proper wavelength, and the presence of molecular oxygen. A model for tissue response to PDT based on the photodynamic threshold dose (D(th)) has been widely used. In this model cells exposed to doses below D(th) survive while at doses above the D(th) necrosis takes place. OBJECTIVE: This study evaluated the light D(th) values by using two different methods of determination. One model concerns the depth of necrosis and the other the width of superficial necrosis. MATERIALS AND METHODS: Using normal rat liver we investigated the depth and width of necrosis induced by PDT when a laser with a gaussian intensity profile is used. Different light doses, photosensitizers (Photogem, Photofrin, Photosan, Foscan, Photodithazine, and Radachlorin), and concentrations were employed. Each experiment was performed on five animals and the average and standard deviations were calculated. RESULTS: A simple depth and width of necrosis model analysis allows us to determine the threshold dose by measuring both depth and surface data. Comparison shows that both measurements provide the same value within the degree of experimental error. CONCLUSION: This work demonstrates that by knowing the extent of the superficial necrotic area of a target tissue irradiated by a gaussian light beam, it is possible to estimate the threshold dose. This technique may find application where the determination of D(th) must be done without cutting the tissue.

PDT experience in Brazil: A regional profile.

The success of PDT and its establishment into the existent hall of therapeutic modalities depends on the collection of reported experiences from around the world. In that sense, it is important to report approaches taken by different countries and what their views are on the future of PDT. Following this idea, we present our clinical experience in photodynamic therapy (PDT) in Brazil, as well as the experimental advances coming up in parallel with clinical implementation. This report is a consequence of pioneering work in a collaborative program involving the Physics Institute in São Carlos, São Paulo State (SP), Brazil, the Medical School of the University of São Paulo, Ribeirão Preto, SP, Brazil and the Cancer Hospital Amaral Carvalho, Jaú, SP, Brazil. This collaborative program, begun in 1997, with the first patient treated in 1999, has treated over 400 patients by late 2004. About 80% of lesions were located in the head and neck or skin, but experience is being built in esophagus, bladder, gynecology, and cutaneous recurrence of breast cancer, among others. The overall results have shown to be compatible with previously reported data. Modifications, whose goal is to improve patient benefit and optimize results, are being implemented as we gain experience. In parallel with the clinical development, several laboratories have started studying experimental whose purpose is to analyze the clinical results and to contribute to the worldwide effort to bring PDT to the forefront of therapies offered to patients. We present the overall results of our 5 years experience as well as the whole implementation process.

Pharmacokinetics of Photogem using fluorescence monitoring in Wistar rats.

In this study we investigated the pharmacokinetics of a hematoporphyrin derivative (Photogem) in Wistar rats using the fluorescence spectroscopy to evaluate the drug distribution in liver, kidney and skin tissues. The detection system is composed of a 532 nm exciting laser, a Y-type catheter for light delivery and collection, a monochromator and a computer for data acquisition. The analysis of the fluorescence spectra was based on the intensity of porphyrin emission bands from specific tissues of the investigated organ. A simple transport model is proposed to determine the accumulation and elimination times for each type of investigated tissue. The obtained results show the viability of the fluorescence spectroscopic technique for the drug concentration monitoring in different target tissues and related pharmacokinetics. These effects should be considered before any in vivo study of Photodynamic Therapy using Photogem.

Experimental derivation of wall correction factors for ionization chambers used in high dose rate 192Ir source calibration.

At present there are no specific primary standards for 192Ir high dose rate sources used in brachytherapy. Traceability to primary standards is guaranteed through the method recommended by the AAPM that derives the air kerma calibration factor for the 192Ir gamma rays as the average of the air kerma calibration factors for x-rays and 137Cs gamma-rays or the Maréchal et al. method that uses the energy-weighted air kerma calibration factors for 250 kV x rays and 60Co gamma rays as the air kerma calibration factor for the 192Ir gamma rays. In order to use these methods, it is necessary to use the same buildup cap for all energies and the appropriate wall correction factor for each chamber. This work describes experimental work used to derive the A(W) for four different ionization chambers and different buildup cap materials for the three energies involved in the Maréchal et al. method. The A(W) for the two most common ionization chambers used in hospitals, the Farmer NE 2571 and PTW N30001 is 0.995 and 0.997, respectively, for 250 kV x rays, 0.982 and 0.985 for 192Ir gamma rays, and 0.979 and 0.991 for 60Co gamma rays, all for a PMMA build-up cap of 0.550 gm cm(-2). A comparison between the experimental values and Monte Carlo calculations shows an agreement better than 0.9%. Availability of the A(W) correction factors for all commercial chambers allows users of the in-air calibration jig, provided by the manufacturer, to alternatively use the Maréchal et al. method. Calibration laboratories may also used this method for calibration of a well-type ionization chamber with a comparable accuracy to the AAPM method.

Photodynamic therapy: a new concept in medical treatment.

A new concept in the therapy of both neoplastic and non-neoplastic diseases is discussed in this article. Photodynamic therapy (PDT) involves light activation, in the presence of molecular oxygen, of certain dyes that are taken up by the target tissue. These dyes are termed photosensitizers. The mechanism of interaction of the photosensitizers and light is discussed, along with the effects produced in the target tissue. The present status of clinical PDT is discussed along with the newer photosensitizers being used and their clinical roles. Despite the promising results from earlier clinical trials of PDT, considerable additional work is needed to bring this new modality of treatment into modern clinical practice. Improvements in the area of light source delivery, light dosimetry and the computation of models of treatment are necessary to standardize treatments and ensure proper treatment delivery. Finally, quality assurance issues in the treatment process should be introduced.

A graphite transmission ionization chamber.

A pancake-type transmission chamber made of high-purity graphite and open to the atmosphere has been designed and constructed at the Secondary Standard Dosimetry Laboratory (SSDL-Rio de Janeiro). Tests performed on the chamber following the International Electrotechnical Commission recommendations indicate that its performance characteristics are comparable to those expected from a secondary standard ionization chamber.