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.

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases;
however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account
for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are
not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet
oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the
long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced
fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ
(75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was
delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen
concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for
the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier
analyses for LCR were done for an endpoint of tumor volume ≤ 100 mm3 using four dose metrics: light fluence,
photosensitizer photobleaching rate, PDT dose, and [1O2]rx. PDT dose was defined as the product of the timeintegral
of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better
correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

Parameterization of electron beam output factor

Photosensitizer fluorescence emitted during photodynamic therapy (PDT) is of interest for monitoring the local concentration of the photosensitizer and its photobleaching. In this study, we use Monte Carlo (MC) simulations to evaluate the relationship between treatment light and fluorescence, both collected by an isotropic detector placed on the surface of the tissue. In treatment of the thoracic and peritoneal cavities, the light source position changes continually. The MC program is designed to simulate an infinitely broad photon beam incident on the tissue at various angles to determine the effect of angle. For each of the absorbed photons, a fixed number of fluorescence photons are generated and traced. The theoretical results from the MC simulation show that the angle theta has little effect on both the measured fluorescence and the ratio of fluorescence to diffuse reflectance. However, changes in the absorption and scattering coefficients, μa and μ's do cause the fluorescence and ratio to change, indicating that a correction for optical properties will be needed for absolute fluorescence quantification. Experiments in tissue-simulating phantoms confirm that an empirical correction can accurately recover the sensitizer concentration over a physiologically relevant range of optical properties.

A theoretical and experimental examination of fluorescence in enclosed cavities

PURPOSE To quantify the dosimetric consequences of pancreatic tumor motion on the pancreatic intensity-modulated radiation therapy (IMRT) plans. METHODS Dose map of IMRT plans for 5 patients with pancreatic cancer were measured using a 2D diode array placed on a computer-controlled platform to simulate 2D pancreatic tumor motion. Dosimetric analysis was then performed to obtain IMRT quality assurance (QA) passing rates. The convolution method, which used a motion kernel to simulate 2D pancreatic motion, was also applied to the treatment and phantom verification plans for a wide range of magnitudes of motion (0.8-2.0 cm). The resulting motion-convolved verification dose maps (VDMs) were compared with the dynamic measurements to evaluate IMRT QA passing rates as well as the dose-volume histogram, the V95% of the planning target volume (PTV) and V98% of the clinical target volume (CTV). RESULTS While CTV coverage was maintained when the simulated pancreatic tumor drifted inside the PTV with magnitudes of 1.0 cm and 1.5 cm, the V95% of the PTV was reduced by 10% and 17%, respectively. We also found that the differences between the measurements and the static VDMs increased proportional to the amplitude of motion, while the agreement between the measurements and the motion-convolved VDMs was excellent for any magnitude of motion. CONCLUSIONS When the 4D technique is not available, predetermined margins must be used carefully to avoid possible under-dose to the target. Additionally, the phantom results show that the kernel convolution method provides an accurate evaluation of the dosimetric impact due to tumor motion and it should be employed in the planning process.

Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

An improved interstitial diffuse optical tomography (iDOT) system has been developed to characterize the optical properties of prostate gland during the photodynamic therapy (PDT). Multiple cylindrical light diffusers with different lengths (instead of point sources used in an earlier version) and isotropic detectors are introduced interstitially in the prostate gland in-vivo. During the data acquisition, linear sources and detectors are stepping into prostate sequentially controlled by a motorized system. A computerized multi-channel attenuator system is developed to automatically control the power strength of each linear source and on times to speed up data acquisition. Three dimensional optical properties are obtained by solving the inverse problem of steady-state diffusion equation based on an adjoint model with Moore-Penrose scheme. The convergence, accuracy and the speed of the algorithms are tested in mathematical phantoms and in prostate simulating phantoms with known optical properties. For comparison, the optical properties of tissue simulating phantoms are also reconstructed using iDOT with multiple isotropic point sources. Data acquisition time in iDOT using linear sources is at least 10 times faster than using the point sources with the total data acquisition time to be less than 1 minutes. Reconstruction results showed both algorithms can successfully recover the optical properties. Reconstruction using linear sources/detectors acquisition mode is 20 times faster than the point sources/detectors method (30 minutes vs. 4 hours on a 3.4 GHz Pentium PC with 4 GB memory). We have demonstrated that linear-source/detector acquisition mode out-performs the point-source mode, and is more practical to be implemented in the clinical settings.

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Timothy C. Zhu

Papers

Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

Parameterization of electron beam output factor

A theoretical and experimental examination of fluorescence in enclosed cavities

Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

Interstitial diffuse optical tomography using an adjoint model with linear sources.