WO1993021842A1 - Diodes electroluminescentes tres puissantes destinees a la therapie photodynamique - Google Patents

Diodes electroluminescentes tres puissantes destinees a la therapie photodynamique Download PDF

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Publication number
WO1993021842A1
WO1993021842A1 PCT/US1993/001893 US9301893W WO9321842A1 WO 1993021842 A1 WO1993021842 A1 WO 1993021842A1 US 9301893 W US9301893 W US 9301893W WO 9321842 A1 WO9321842 A1 WO 9321842A1
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WIPO (PCT)
Prior art keywords
light
array
emitting diodes
photosensitizer
wavelength band
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PCT/US1993/001893
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English (en)
Inventor
Robert D. Bower
Michael D. L. Stonefield
Elizabeth M. Waterfield
Edwin M. Sakaguchi
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Quadra Logic Technologies, Inc.
American Cyanimid Company
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Application filed by Quadra Logic Technologies, Inc., American Cyanimid Company filed Critical Quadra Logic Technologies, Inc.
Publication of WO1993021842A1 publication Critical patent/WO1993021842A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00017—Electrical control of surgical instruments
    • A61B2017/00022—Sensing or detecting at the treatment site
    • A61B2017/00057—Light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
    • A61N2005/0642—Irradiating part of the body at a certain distance
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/065—Light sources therefor
    • A61N2005/0651—Diodes
    • A61N2005/0652—Arrays of diodes

Definitions

  • the invention generally relates to the use of high-power light-emitting diodes (LEDs) for use in photodynamic therapy (PDT) . More specifically, high- power LEDs emitting a suitable wavelength band are used to activate photosensitive drugs for in vitro, extracorporeal, or in vivo PDT. The aim is to selectively impair or destroy targeted cancerous or otherwise undesirable tissues or cells while leaving healthy tissues or cells unaffected.
  • LEDs light-emitting diodes
  • PDT photodynamic therapy
  • PDT or photodynamic therapy has become a recognized means of treating certain types of cancer.
  • a review of many of the areas in which it has been applied is given by S.L. Marcus in 'Proceedings of the IEEE' (in publication) .
  • a photosensitizer such as PHOTOFRIN ® porfimer sodium or BPD (benzoporphyrin derivative) is administered systemically to a patient with cancer.
  • The• drug distributes through the body in such a manner that it is found in higher concentrations at the diseased site. This can take several hours to a few days depending on the drug.
  • a suitable light source is then used to activate the drug in the tissue.
  • an alternative scenario to the above would be one in which the drug is administered topically to the target tissue, e.g., a psoriatic lesion, site of viral infection, wart, or port wine stain.
  • the light source can be directed at the target to activate the drug, either via a fiber or by direct illumination.
  • photosensitizing compounds have been tested in vivo as potential clinical photosensitizing drugs, including PHOTOFRIN* and its precursor hematoporphyrin derivative, BPD, chloroaluminum p ⁇ ithalocyanine tetrasulfonate, zinc phthalocyanine tetrasulfonate, protoporphyrin IX, purpurin, merocyanine 540, methylene blue, tetraphenylporphyrin sulfonate, pheophorbide, monoaspartyl chlorin e6.
  • These photosensitizers are activatable by light in the 500 nm to 780 nm range.
  • the mechanisms by which PDT works are complex, and the activation mechanisms may dif er from one photosensitizer to another.
  • a feature common to all of these photosensitizers is that they are activated by the absorption of light.
  • the wavelength of light must coincide with a suitable photosensitizer absorption band.
  • the absorption results in energy being deposited into the photosensitizer and subsequently initiates a series of chemical reactions which result in the death of cells. Since the energy is deposited only where the photosensitizer is located, only cells local to the photosensitizer are killed. The result of the cells' death depends on the treatment being performed.
  • the photosensitizer in the case of photosensitizers such as PHOTOFRIN*, where the PDT is being done to eradicate a tumor, this cell killing appears to give rise to both localized destruction of the tumor tissues and to local vascular damage to the blood vessels supplying the tumor.
  • the net result for correctly applied light and photosensitizer doses is for the tumor to be killed but not the surrounding healthy tissues.
  • the photosensitizer should have a strong absorption band, and the energy deposited into the photosensitizer should be efficiently converted into chemical reactivity.
  • a photosensitizer in a singlet ground state is promoted into an excited singlet electronic state by photon absorption.
  • the excited singlet state will have a radiative lifetime on the order of a few nanoseconds. Vibrational relaxation within the excited singlet state to the lowest vibrational levels is rapid (10 12 s—1) .
  • the excited singlet state can emit a photon, undergo a spin-allowed internal conversion to the ground singlet state, undergo a spin-forbidden intersystem crossing into a triplet state, react, or transfer its energy to another molecule.
  • a photosensitizer is chosen such that significant production of the triplet state occurs.
  • the triplet state will then vibrationally relax to the minimum energy of the triplet state. If the triplet state is of lower energy than the excited singlet state, the triplet state will not execute an intersystem cross-back into the excited singlet state. If there is large energy gap between the ground singlet state and the triplet state, then intersystem crossing from the triplet state into the ground state is typically slow. Since a triplet-to-singlet radiative transition is spin- forbidden, phosphorescence will not be a major loss mechanism. Therefore, the light energy is stored in the photosensitizer's etastable triplet state. There are three major deactivation mechanisms for this triplet state: internal conversion into the ground singlet state, reaction of the triplet state, and energy transfer from the triplet state.
  • the metastable triplet's energy is converted into energy in the singlet ground state. If vibrational relaxation in the ground state is fast, then the result is localized heating. This heating may kill cells by thermal effects. If the singlet state's energy is greater than bond- dissociation energy, then dissociation of the photosensitizer may occur resulting in the formation of radicals or radical ions, both of which may initiate chemical reactions resulting in the localized killing of cells. The second possibility is that the excited triplet state reacts. Either or both of these reactions may cause cell death. The third mechanism is energy transfer from the excited triplet state to some other molecule, which then initiates a chemical reaction. A molecule which is frequently the receptor of triplet energy is oxygen. Ground state triplet oxygen and triplet state photosensitizer undergo a spin-allowed energy transfer to produce ground singlet state photosensitizer and excited singlet oxygen. This singlet oxygen causes oxidation reactions which kill the cell.
  • the distance the singlet oxygen travels in an in vivo or in vitro environment is limited by how far it can diffuse during its lifetime. Since singlet oxygen has a lifetime of 5 ⁇ s in water, it can travel 20 ⁇ m. Therefore, the toxic effect is very localized around the photosensitizer.
  • the first two mechanisms lead to reactions often referred to as Type 1, while the third mechanism produces reactions of Type 2.
  • a schematic of these two reactions is shown in Figure 1. If the photosensitizer dissociates or reacts, the photosensitizer is destroyed and cannot participate further in the destruction of cells. However, if the cell-killing mechanism is primarily due to localized thermal or energy transfer, then the photosensitizer is returned to the ground state, from which it can absorb another photon.
  • a single photosensitizer molecule can produce a large number of singlet oxygen molecules. It is generally believed that the Type 2 reaction with oxygen is the dominant reaction in PDT.
  • the light source must satisfy several requirements. It must emit a suitable wavelength or band of wavelengths for activating the photosensitizer. It should be focusable into a fiber optic for PDT that requires a precise geometry of illumination (e.g., spherical or cylindrical), or for PDT performed in areas that cannot be directly illuminated by the light source (e.g., endoscopic procedures - lung, esophagus, bladder) . In addition it should have an output power high enough to ensure that the required light dose can be delivered to the patient in a reasonable time. It also should have a suitable pulsed or continuous wave (cw) characteristic, so that the light interacts effectively with the drug and does not damage healthy tissues or the optic that transmit or reflect the light.
  • cw pulsed or continuous wave
  • the high peak power associated with a single pulse can damage tissue or fiber optic by a number of mechanisms. These mechanisms include ablation, thermal effects and acoustic shock waves. Similarly, if the cw power is too high, then direct damage to the tissue can result such as dehydration and charring. A more complete discussion of various aspects of these mechanisms is given in the 'Proceedings of "Laset-Tissue Interaction" Con erence', SP ⁇ E, Vol. 1202 (1990).
  • pulsed lasers In general, average laser powers of a few watts are used, the maximum power being limited by existing sources of high-power lasers that operate at the correct wavelengths.
  • pulsed lasers are usually systems of high pulse repetition rate (1 kHz or higher) , with a low output energy/shot (about 1 mJ) . It is the power density (intensity) of the light that determines the effect of the light on the targeted tissue. Power densities of 10-200 mW/c are typically used for PDT. These are too low to significantly heat up the tissue, but are adequate to activate the photosensitizer, producing the desired effect in a time that is short enough for clinical treatment, this typically being less than 1 hour or so.
  • Patented examples of specific lasers being used for PDT may be found in U.S. Patent 4,336,809 to Clark, which discloses a xenon-ion laser, and U.S. Patent 4,614,190 to Stanco et al., which discloses a pulsed- laser photoradiation scheme. Both of these are complex gas-laser-based technologies. Many other practical examples of these and other lasers being used in clinical procedures exist within the scientific and medical literature.
  • U.S. Patent 4,757,431 to CROSS discloses the use of off- axis concave spherical reflectors as condensing and collecting optics to couple the optical output of a xenon arc lamp efficiently into a single fiber.
  • U.S. Patent 4,860,172 to Schlager et al. discloses the use of a tapered coupling cone to concentrate the focused optical output of an arc lamp that is mounted in a parabolic reflector, so enabling higher optical powers to be coupled into a fiber.
  • the devices are physically very large. They have a poor wall-plug efficiency, where this is defined with respect to the electrical power input relative to the laser power output. This results in a requirement for substantial electrical power needs and special main supply outlets rather than the normal house wall-plug socket. They require water or air cooling. They are not very portable. They require periodic realignment by a trained engineer. They require a warm-up time before use and a cool-down time after use. They are very expensive and have substantial maintenance costs. They are limited in the total power they can output in the wavelength range of interest.
  • LEDs Light-emitting diodes
  • cw continuous wave
  • the LEDs When the LEDs are combined into a suitable array, then power densities up to 200 mW/cm 2 can be obtained. This power density is equivalent to that now being provided by lasers in PDT.
  • semiconductor material structures include AlGaAs and GalnP/AlGalnP, which can be designed to access wavelengths in the 600-900 nm range by carefully adjusting the parameters used to make the device.
  • LEDs at a variety of wavelengths are available from commercial suppliers and are described in company literature, e.g, Hewlett-Packard, Toshiba and Sony.
  • This dual wavelength excitation was believed to access a specific excitation route of the photosensitizer, this being 630 nm excitation to the singlet excited electronic state, followed by the radiationless formation of a triplet excited state, at which point a 690 nm photon would excite the photosensitizer into a higher triplet excited state prior to the usual Type 1 and Type 2 reactions that have been described earlier.
  • the inventors used At the low power levels the inventors used, they achieved incomplete activation of the drug, and minimal cytotoxicity was observed after 48 hours. They advocate using arrays of photodiodes to treat the target tissues, whereby these arrays would be made up of equal numbers of the two types of photodiode required. The long durations required to kill the target cells with the method advocated by Kawai et al. would not be suitable for any clinical treatment.
  • the invention comprises high-power LED systems that use a single wavelength band to photoactivate the drug within a clinically acceptable time of an hour or so.
  • the wavelength band is centered around a suitable absorption band of the photosensitizer.
  • the LEDs are configured into arrays that permit PDT treatment of skin and mucosal tissues, and extracorporeal, in vitro, and intraoperative applications, e.g., psoriasis, papilloma virus, port wine stains, bone marrow purging, ovarian cancer surgery. None of these applications require the light to be delivered to the target area by a fiber optic system because they can all be directly illuminated by a suitably positioned LED array.
  • a multiplicity of LEDs can be assembled into a system with their optical power adding together to produce a combined power output that is suitable for PDT over large areas.
  • the maximum power attained is limited only by the number of LEDs that are combined in the particular system.
  • the LEDs are normally connected in arrays, it is the cumulative power density that is normally measured rather than the power of a single LED; i.e., over an array surface the LEDs are configured to produce the power density needed for the particular treatment.
  • Using large-area LED arrays would permit scaling of some of the existing PDT procedures which currently are limited by the powers available from conventional laser sources.
  • the LEDs can be specifically engineered to produce the desired wavelength output for activating almost any photosensitive drug.
  • photosensitizing drugs include PHOTOFRIN ® which is activated at around 630 nm, BPD at around 690 nm, and the phthalocyanines and purpurins in the 650-680 nm range. All of these drugs have fairly broad absorption bands, so an ultranarrow laser bandwidth source is not necessary to activate the photosensitizer. It is this broad absorption band that permits LEDs to be used as a replacement for the more conventional laser source, because although LEDs typically have a bandwidth of 20- 30 nm, the optical power within this bandwidth is able to interact with the photosensitizer.
  • LEDs are ideal for PDT as they can be made into compact systems and so can be truly transportable. They have very high wall-plug efficiencies (generally >10% in comparison to the more typical 1% or less of conventional lasers) and so can be powered directly from a standard wall-plug socket rather than a special high power supply. They require little or no air or water cooling. They can be used immediately after being switched on and can be switched off with no major cool-down cycle. LEDs are mass-producible, can be made into a compact integrated package, and are cheap*. They require no maintenance, and so systems assembled from them have little or no maintenance costs. Power feedback and wavelength monitoring can be built into a system to ensure that the optical parameters do not change during the treatment, this being very important if the correct light dose is to be delivered.
  • LEDs have a number of other advantages. They operate at low voltages of about 2 V, so they can be packaged into systems that are powered from a wall socket or a battery pack. These low voltages also simplify compliance with electrical safety and medical requirements: they can be easily carried or wheeled around on a small trolley, or assembled into shapes or sizes appropriate for specialized applications.
  • the monolithic structure of the LEDs makes it simple to design systems that can satisfy the requirements for sterility in a hospital environment. It is possible to connect LEDs together in a variety of ways so that the voltage-current requirements are tailored to the electrical power supply that is available.
  • Figure 1 is a schematic of the Type 1 and Type 2 photochemical reactions of photosensitizers.
  • Figure 2 is an absorption spectrum of BPD in ethanol, showing the typical broad absorption band in the red, around 690 nm, as well as the extended absorption down into shorter wavelengths. Also, the absorption of oxyhemoglobin is superimposed showing the reduction in oxyhemoglobin absorption as longer wavelengths in the red are used, i.e., as more light penetrates the tissue to interact with the drug.
  • the y-axis denotes the molar extinction coefficients.
  • Figure 3 is a typical emission spectrum of a Hewlett-Packard LED centered at 694 nm with a full-width half-maximum (FWHM) bandwidth of 25 nm.
  • FWHM full-width half-maximum
  • Figure 4 is a block diagram of the overall system concept.
  • Figure 5 is a block diagram illustrating ways in which LEDs can be connected up so that their optical powers add to give a single broad-area light output with a predictable light intensity: (a) shows overlapping beams from each LED, (b) shows simple rows of LEDs all equally spaced, (c) shows the doubling of power density available from (b) that can be achieved by inserting additional rows of LEDs.
  • Figure 6 shows the change in the central wavelength of light emission from 690 nm LEDs as the operating temperature of the system is changed.
  • Figure 7 shows the change in the system temperature of an array of LEDs mounted on a board as the input electrical power is increased.
  • Figure 8 shows the shift in the central wavelength of the LEDs as the input electrical current is increased.
  • Figure 9 shows the shift in wavelength of the overall spectrum of light emission from the LEDs and the associated increase in light intensity as the electrical current input is increased.
  • Figure 10 shows the change in light intensity output when electrical current input is varied.
  • Figure 11 shows the change in power density with increasing distance from a 3.5 cm x 3.5 cm array.
  • Figure 12 shows the uniformity of light intensity from a 3.5 cm x 3.5 cm area array.
  • Figure 13 shows a typical geometry of LEDs incorporating a lens (Hewlett-Packard data sheet, type Tl) .
  • Figure 14 shows how the LEDs can be incorporated into specific geometries for treating an entire person, part of that person, or a sample area of the tissue or cells of interest.
  • Figure 15 shows results of the in vitro cytotoxic dose response (MTT assay) , with the percent killed or impaired being compared to the controls (0.0 ⁇ g BPD) , for a LED array and the argon ion-pumped dye laser (APDL) .
  • Figure 16 is an in vivo equivalency study showing the percentage of animals tumor-free from day 0 and day 20 after exposure to the APDL and the LED array;
  • the LEDs will be chosen such that they efficiently and specifically activate the desired photosensitizer.
  • wavelengths in the range of 630 ⁇ 30 nm would be suitable.
  • wavelengths in the range of 690 ⁇ 30 nm would be suitable.
  • An excitation wavelength can be generalized in this way and still be effective in activating the photosensitizers because their absorption bands are fairly broad, those for BPD being shown in Figure 2.
  • 690 nm can be compared to that of a typical 690 nm LED source that is shown in Figure 3. These LEDs are based on a transparent substrate AlGaAs material, and are obtained from Hewlett-Packard (product type Tl TS AlGaAs 690 nm) . The FWHM of the LED spectrum is about 25 nm. this being similar to that of the 690 nm BPD absorption band.
  • absorption bands that can be accessed by a LED
  • the one used will be determined by the treatment being performed. In general, maximum penetration of light into the tissue to be treated is required, and this necessitates the use of longer wavelengths in the red and near infrared. However, under circumstances where there is a specific requirement to treat to a well-defined depth, then a shorter wavelength of light can be used to activate the drug, thus limiting the depth of light penetration.
  • PHOTOFRIN* Various types of photosensitizers can be used in conjunction with this technology, including PHOTOFRIN* and BPD, which can be obtained from Quadra Logic Technologies, Inc., Vancouver, B.C., Canada.
  • Power source 1 can be either an AC-to- DC supply or a battery source.
  • the LEDs can be designed into the system in such a way that they can be disposed of either with the system, or as a disposable component that is replaced by a new plug-in LED module 2. Typically, this type of LED has a life of over 10,000 hours, although this is a strong function of the electrical current and cooling. If another wavelength is needed to activate the particular photosensitizer in use, then another LED module 2 with a suitable wavelength output can be connected.
  • Feedback loop 3 monitors the LED power output via photodiode detectors (output light power is sampled) and via the electrical current being supplied to the LED.
  • the signal detected by either of these methods can be used to stabilize the LED light power output by comparing it to previously set reference levels and adjusting the electrical power input to compensate for any changes detected.
  • a second feedback loop 4 can be connected to an external dosimetry system that monitors either the light actually delivered to the tissue or the real-time phototherapeutic effect at the target 5, cutting off the light output when the desired light dose or effect has been achieved.
  • the LED light output can be cut off during or after treatment simply by cutting the electrical power.
  • a low power output can be easily obtained for alignment purposes prior to treatment either by having a preset low electrical power input or a variable input power supply.
  • LEDs Other features that are incorporated into existing PDT light sources that aid the user of the device can also be used with LEDs. Examples of these include built-in timers used to calculate the light dose delivered, green LEDs or backlit LCD displays that can be read even while wearing laser safety goggles (the goggles filter out the red display panel figures) .
  • the output should be cw, this is not an essential requirement, and a LED array that is pulsed will work provided that its pulse characteristics are suitable for activating the drug and its average power-is high enough.
  • FIG. 5 illustrates how the LEDs are connected together to form an array with the output of all the elements adding together. A uniform power density is obtained in the center of the array, with the power density dropping off as the edges of the array are reached and passed, this being shown in more detail in Figure 13.
  • the packing density of the LEDs in the array is also critical in determining the power density that can be obtained from it. This can be understood very easily if one considers that if each LED has a fixed power output of, for example, 5 mW, the number of LEDs/cm multiplied by this power output will determine the power density m mW/cm 2. As the number of LEDs/unit area is increased, the maximum power density that can be obtained from the array increases proportionately; a method by which this is done is shown in Figures 5(b) and 5(c). The physical size of each LED in its mounting and the problems of removing the heat from the LED array ultimately limit the maximum packing density that can be used. In Figure 5(a), 11 refers to the circuit board of PCB to which the LEDs are connected, 12 refers to the individual LEDs, and 13 is the region in which their beams overlap.
  • Figure 6 shows the shift in the central wavelength of the LEDs as the temperature changes, this being about 0.25 nm/°C for these LEDs.
  • optical power m the range of 0-200 mW/cm can readily be obtained with a suitably designed array.
  • Figures 5 to 10 illustrate that with judicious use of cooling (for example, using forced air or water) and careful selection of the operating electrical current for a fixed LED packing density, the central wavelength of the wavelength band from the LEDs can be set to coincide with an absorption peak of a photosensitizer while operating at a predetermined power output.
  • the above parameters would be preset during manufacture for the particular device in question, so that the hospital operator would not have to make adjustments to the device once it was installed.
  • the change in power density as one goes farther away from an array is shown in Figure 11, where this array is 3.5 cm x 3.5 cm. This shows that the light intensity drops fairly rapidly as the distance increases.
  • a calibrated photodiode that takes into account the optical transmission of the fiber detector system is used to determine the light density at that point.
  • Figure 13 shows a typical LED (the one used to collect the data for this patent) that is available from Hewlett-Packard. This design incorporates a lens so that the light is emitted as a beam with a solid angle of about 0.6 steradians.
  • Figures 14a through 14c show examples of a number of geometries that the LEDs can be configured into, some of which take advantage of this ability to combine a number of panels together.
  • Figure 14a illustrates the use of LEDs mounted to form an array on a flexible or folded circuit board. The numbering here denotes: the LEDs 21 mounted on the circuit boards 22, and the emitted light 23 incident on the target 24. As is shown here, this could be used to treat localized tissue areas with curved surfaces, e.g., the arm or leg, or areas opened up for surgery.
  • Figure 14b shows large area panels connected to form a box, or "entire body phototherapy system.” This system could be used to treat patients with extensive psoriasis.
  • two panels 27 and 28 carry light emitting diodes which emit light 26 and 26, respectively, onto target 29. If required front and back panels may include light emitting diodes too.
  • Figure 14c shows the use of a simple panel of LEDs for a localized cutaneous treatment of tissue, e.g., basal cell carcinoma or port wine stains.
  • Light emitting diodes 31 mounted on panel 32 emit light 33 onto the treatment area of target 34
  • the way in which the LED arrays are connected to the control unit will depend on the clinical operation.
  • One method is to have an array of LEDs, designed to activate a specific drug, attached via an umbilical line to the control unit.
  • the umbilical line will carry power to the LEDs as well as relaying information on their operating optical power output and temperature, etc. back to the control unit.
  • This geometry is useful where the maximum flexibility is needed in positioning the array because of space constrains.
  • the LED arrays can be connected directly to the control unit, and again different LED panels can be substituted in as different wavelengths are needed to activate different drugs, or achieve greater or less penetration of light into tissue.
  • the photosensitizer is BPD-MA (monacid form of BPD) activated by LEDs operating at wavelengths centered around 690 nm.
  • Example 2 Male DBA/2 CR mice were implanted with Ml-S (rhabdomyosarcoma) cells 10 to 12 days prior to the experiment and depilated 6-7 days later. Animals carrying 5-mm diameter tumors were dosed i.v. with a single dose of liposome-formulated BPD-MA (2.0 mg/kg). The mice were rested for 3 hours in the dark before exposure to light.
  • Ml-S rhabdomyosarcoma
  • Irradiation was carried out using either an APDL tuned to 690 nm, or an LED array with a 25-nm bandwidth centered at 696 nm.
  • the anti-tumor efficacy data is presented in Figure 16: At day 7, 100% of the mice exposed to LED light were tumor free; at day 14, 40% were tumor free; at day 20, 20% were tumor free. These curves show that a significant anti ⁇ tumor effect was obtained in vivo with the LED array and the laser under identical treatment regimes.

Abstract

Procédé et système permettant d'activer des photosensibilisateurs utilisés dans la thérapie photodynamique (TPD) réalisée in vivo, à l'extérieur du corps, et in vitro, dans lesquels les sources de lumière employées sont de très puissantes diodes électroluminescentes (DEL) dont la sortie de bande de longueur d'onde est sélectionnée pour activer une bande d'absorption donnée du photosensibilisateur. Ce système comprend une alimentation électrique (1), un réseau de diodes électroluminescentes (2), une boucle (3) de rétroaction destinée à surveiller la puissance de sortie des diodes électroluminescentes et une boucle (4) de rétroaction servant à surveiller la lumière distribuée sur une zone cible (5).
PCT/US1993/001893 1992-04-30 1993-02-22 Diodes electroluminescentes tres puissantes destinees a la therapie photodynamique WO1993021842A1 (fr)

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WO1998003224A1 (fr) * 1996-07-19 1998-01-29 Theratechnologies R & D Inc. Appareil d'exposition aux rayonnements utilisant une source de lumiere balayante pour traitement photodynamique
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WO1998052644A1 (fr) * 1997-05-23 1998-11-26 Hofmann Guenther Systeme pour le traitement photodynamique d'etres vivants, de leurs organes et/ou de leurs tissus
EP0885018A1 (fr) † 1996-11-19 1998-12-23 Baxter International Inc. Procede permettant d'inactiver des contaminants dans un liquide biologique et appareil correspondant
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