The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology--to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work, and how can it be used to treat cancer and other diseases?

Photodynamic therapy for cancer

CA : A Cancer Journal for Clinicians

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. CA Cancer J Clin 2011;61:250-281. V C

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Photodynamic therapy of cancer: An update†‡

A review of reported tissue optical properties summarizes the wavelength-dependent behavior of scattering and absorption. Formulae are presented for generating the optical properties of a generic tissue with variable amounts of absorbing chromophores (blood, water, melanin, fat, yellow pigments) and a variable balance between small-scale scatterers and large-scale scatterers in the ultrastructures of cells and tissues.

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Optical properties of biological tissues: a review.

Singlet oxygen (1O2) is the major cytotoxic agent for type II photodynamic therapy (PDT). The production of 1O2 involves the complex reactions among light, oxygen molecule, and photosensitizer. From universal macroscopic kinetic equations which describe the photochemical processes of PDT, the reacted 1O2 concentration, [1O2]rx, with cell target can be expressed in a form related to time integration of the product of 1O2 quantum yield and the PDT dose rate. The object of this study is to develop optimization procedures that account for the optical heterogeneity of the patient prostate, the tissue photosensitizer concentrations, and tissue oxygenation, thereby enable delivery of uniform reacted singlet oxygen to the gland. We use the heterogeneous optical properties measured for a patient prostate to calculate a light fluence kernel. Several methods are used to optimize the positions and intensities of CDFs. The Cimmino feasibility algorithm, which is fast, linear, and always converges reliably, is applied as a search tool to optimize the weights of the light sources at each step of the iterative selection. Maximum and minimum dose limits chosen for sample points in the prostate constrain the solution for the intensities of the linear light sources. The study shows that optimization of individual light source positions and intensities is feasible for the heterogeneous prostate during PDT. To study how different photosensitizer distributions as well as tissue oxygenation in the prostate affect optimization, comparisons of light fluence rate were made with measured distribution of photosensitizer in prostate under different tissue oxygenation conditions.

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A heterogeneous optimization algorithm for reacted singlet oxygen for interstitial PDT

Abbreviations: AK, Actinic Keratosis; ALA, aminolevulinic acid; AMD, age-related macular degeneration; BCC, Basal cell carcinoma; BPD-MA, benzoporphyrin derivative monoacid A, CNV, Choroidal neovascularization; CW, continuous wave; FDA, Food and Drug Administration; Hb, hemoglobin; HPD, hematoporphyrin derivative; ISC, Intersystem crossing; LED, light-emitting diode; MLu, motexafin lutetium; mTHPC, meso-tetrahydroyphenol chlorin; PDT, Photodynamic therapy; PIT, photoimunotherapy; PpIX, protoporphyrin IX; SCC, Squamous cell carcinoma;

/pdf/photodynamic-therapy-fundamentals-and-dosimetry-44jl4gkb9t.pdf

Photodynamic Therapy: Fundamentals and Dosimetry

Determination of in-vivo tissue optical properties for anal photodynamic therapy (PDT) is challenging due to the light integrating-sphere effect in an enclosed cylindrical cavity. We developed a model for optical properties determination for anal PDT from measurements of light fluence rate inside a cylindrical cavity submerged in tissue-mimicking liquid phantoms. Measurements are performed in a set of phantoms with known optical properties (μa = 0.1-0.9 cm-1) and (μs’ = 5.5-16.5 cm-1) and the primary and scatter light fluence rates are determined. We developed a forward empirical model to relate scatter light fluence rate measured in an enclosed cylindrical geometry to the surrounding tissue optical properties in tissue-simulating liquid phantoms.

Determination of in-vivo tissue optical properties for anal photodynamic therapy

Metastable Failures in the Wild

Purpose: The aim of the study was to quantify the effect of miniphantoms on in-air output ratio measurements, i.e., to determine correction factors for in-air output ratio. Methods: Monte Carlo (MC) simulations were performed to simulate in-air output ratio measurements by using miniphantoms made of various materials (PMMA, graphite, copper, brass, and lead) and with different longitudinal thicknesses or depths (2-30 g/cm{sup 2}) in photon beams of 6 and 15 MV, respectively, and with collimator settings ranging from 3x3 to 40x40 cm{sup 2}. EGSnrc and BEAMnrc (2007) software packages were used. Photon energy spectra corresponding to the collimator settings were obtained from BEAMnrc code simulations on a linear accelerator and were used to quantify the components of in-air output ratio correction factors, i.e., attenuation, mass energy absorption, and phantom scatter correction factors. In-air output ratio correction factors as functions of miniphantom material, miniphantom longitudinal thickness, and collimator setting were calculated and compared to a previous experimental study. Results: The in-air output ratio correction factors increase with collimator opening and miniphantom longitudinal thickness for all the materials and for both energies. At small longitudinal thicknesses, the in-air output ratio correction factors for PMMA and graphite are close to 1. The maximummore » magnitudes of the in-air output ratio correction factors occur at the largest collimator setting (40x40 cm{sup 2}) and the largest miniphantom longitudinal thickness (30 g/cm{sup 2}): 1.008{+-}0.001 for 6 MV and 1.012{+-}0.001 for 15 MV, respectively. The MC simulations of the in-air output ratio correction factor confirm the previous experimental study. Conclusions: The study has verified that a correction factor for in-air output ratio can be obtained as a product of attenuation correction factor, mass energy absorption correction factor, and phantom scatter correction factor. The correction factors obtained in the present study can be used in studies involving in-air output ratio measurements using miniphantoms.« less

Timothy C. Zhu

Papers

A heterogeneous optimization algorithm for reacted singlet oxygen for interstitial PDT

Photodynamic Therapy: Fundamentals and Dosimetry

Determination of in-vivo tissue optical properties for anal photodynamic therapy

Metastable Failures in the Wild

Monte Carlo simulation of the effect of miniphantom on in-air output ratio