WO1997040888A1

WO1997040888A1 - Therapy apparatus and method

Info

Publication number: WO1997040888A1
Application number: PCT/EP1997/002078
Authority: WO
Inventors: Robert M. Sayre; James G. Shepherd
Original assignee: Glaxo Group Limited
Priority date: 1996-04-25
Filing date: 1997-04-24
Publication date: 1997-11-06
Also published as: AU2769497A; GB9608484D0

Abstract

A medical illuminator apparatus for photodynamic therapy (PDT) comprising at least one fluorescent lamp mounted in a phototherapy lamp housing and comprising a selected phosphor fluorescent source for emitting yellow, orange and/or red wavelengths and providing a fluence in a desired wavelength band corresponding to the predetermined photoactivated compound, and wherein at least about 70 % of the unfiltered emission from the fluorescent lamp is usable for the PDT.

Description

THERAPYAPPARATUSANDMETHOD

The present invention relates to photodynamic therapy (PDT) and more particularly to an improved apparatus and method for photodynamic therapy utilising a fluorescent lamp for photoactivation of a PDT medicinal drug.

As is well known in the medical field of dermatology, certain medicinal compounds can be photoactivated by light in a treatment called photodynamic therapy (PDT). Photodynamic therapy (PDT) involves the use of light sources to treat a variety of skin disorders such as cancer, psoriasis, keratosis and other types of related skin disorders. The general theory behind PDT is the therapeutic use of light so as to obtain a photoreaction of tissue to the radiation source or, alternatively, to obtain the activation of a topically or systemically administered drug which is light sensitive. For example, it is presently known to treat psoriasis by exposing a patient to ultraviolet radiation in combination with a topically or systemically applied medicament that sensitises the skin to ultraviolet radiation. See, for other examples, U.S. Patent No. 5,079,262; U.S. Patent No. 5,211,938; and PCT Intemationai Publication No. WO 95/11059.

Normally, a photosensitive drug is administered systemically, topically or by injection into a target site such as a tumour in photodynamic therapy (PDT). Irradiation of a target site by an appropriate light source (e.g., an argon-pumped dye laser or a sunlamp) will induce a cytotoxic effect on the cells of the target site by one of two basic treatment procedures that are followed in photodynamic therapy (PDT).

In type one photoactivation, the irradiated drug substance reacts directly with the biological substrate, forming radicals which can initiate subsequent radical reactions which in turn induce cytotoxic damage. Alternatively, in type two photoactivation, energy is transferred from the irradiated drugs to oxygen which thereby produces singlet molecular oxygen which in turn produces cytotoxic oxygenated products. One representative example of such a PDT technique involves the photoactivation of a family of dyes known as porphycenes. In general, the light source for photodynamic therapy (PDT) is selected depending upon the target tissue to be irradiated, the nature of the skin disorder to be treated and/or the photoactivated drug to be delivered to the patient. As is well known to those skilled in the art, certain light sources are selected on the basis of the wavelength of light required to treat a particular skin disorder (e.g., a UV light source to treat psoriasis).

SUBSTΓΓLΠΈ SHEET (RULE 26) In PDT treatment regimens where the light source is used to activate a particular chemical compound, the light source is generally selected so that it emits light energy in the optimal wavelength range required to photoactivate the medicinal compound. The rationale for designing and selecting light sources for use in activating light- activated PDT drugs is based upon the absoφtion spectrum of the drug in the skin and providing light that is primarily absorbed directly by the drug. A secondary concern in PDT therapy is to minimise the irradiation of patients with any light or radiation that can produce an adverse effect or which is absorbed by tissue not being treated with the drug. While various light sources may be used to activate a medicinal compound of interest in PDT since almost all light sources would have some light energy within the wavelength band at which a compound is activated, it is clearly preferential to select a light source which emits wavelengths of light which most closely overlap with the range in wavelengths (or the wavelength band) at which a medicinal compound is activated. For example, the prior art suggests the use of lasers to emit light wherein it is desirable to have light energy emitted in a concentrated narrow beam that is highly specific with regard to wavelength and focused on a restricted surface area. While such an approach is good for matching wavelength with a medicinal compound undergoing photoactivation, it suffers a shortcoming of only allowing for the irradiation of a very small treatment surface area on a patient. As is well known, this is not satisfactory for many PDT treatment regimens that call for the exposure of larger treatment surface areas on a patient.

To provide exposure of larger PDT treatment surface areas on a patient, there is knowledge of only four primary light sources that have been extensively used for PDT to date. These light sources consist of quartz tungsten-halogen, mercury arc, mercury- metal halide and xenon arc lamps. These four known light sources are generally less than optimal for a variety of reasons including that typically a vast amount of their light energy emissions are outside of the desired wavelength region or band that will be absorbed by the PDT medicinal compound during activation thereof. Moreover, all of these light sources (with the exception of quartz tungsten-halogen lamps) pose some risk of explosion so as to require protective housings as well as being difficult to reignite once they have been turned off. Consequently, for most medicinal patient treatment applications, the mercury arc, mercury-metal halide and xenon arc light sources must be shuttered while adjustments are made for additional exposure treatment sites on a patient. Even more significantly, the primary shortcoming of all of the aforementioned light sources is the relatively small amount of light output that is actually available for photoactivation of a medicinal compound. For example, if a quartz tungsten-halogen light source is utilised, only about 10% of the light energy will typically be utilised for activation of a PDT medicinal compound and the remaining 90% of light energy will be dissipated in the form of heat. More specifically, in the case of the light wavelength band absorbed by a PDT medicinal compound such as the dye ATMPn (9-acetoxy- 2,7,12,17-tetrakis(methoxyethyl)-poφhycene) only about 10% of the light energy emitted is actually used to activate the medicinal compound. Accordingly, these four familiar light sources require considerable optical filtration in order to achieve the desired wavelength band to photoactivate a therapeutic compound and considerable cooling capacity to remove the unwanted heat from the environment of the light source.

An additional shortcoming of the aforementioned light sources for broad surface PDT application is the relatively low amount of power available in the desired wavelength band from the light source to photoactivate the medicinal compound. Thus, the use of a high power light source (typically 1 ,000 watts or more) is necessary in order to provide effective PDT treatment. In other words, the known light sources do not have enough power or light energy within the desired wavelength band required to photoactivate a PDT compound without significantly increasing the light source wattage to levels of 1 ,000 or more watts. The high wattage light sources suffer well-known disadvantages including high maintenance expenses due to increased power use and high replacement costs relative to lower wattage light sources.

As an alternative to the high wattage required by known PDT light sources for broad surface PDT treatment, the light sources could be utilised with lower wattage and lengthened patient exposure time. For example, and for the puφoses of discussion only, if effective PDT therapy with a poφhycene medicinal compound is believed to require at least 60 Joules of power in a desired wavelength band to reach the medicinal compound, and if a light source emits 100 milliwatts of power in the desired wavelength band, it would take 600 seconds of irradiation time to deliver the appropriate light treatment energy dose to the patient. On the other hand, if the power level of the emitting source is only 10 milliwatts, then the patient should be exposed to irradiation for 6,000 seconds for comparable treatment efficacy. However, such lengthy patient exposure time is clearly undesirable for obvious reasons, and thus a desirable PDT objective would be to achieve a minimal power level to deliver adequate light energy in

SUBSTTTuTE SHEET (RULE 26) the desired wavelength band to a patient in a reasonable amount of time.

Accordingly, there is a long-felt need in PDT for a cost-effective light source that provides broad treatment surface exposure of light energy in the desired wavelength band while minimising patient exposure time and heat dissipation requirements inherent in high wattage light sources

In accordance with the present invention, there is provided an improved medical illuminator apparatus for activation of a photoactivated compound during photodynamic therapy (PDT). The apparatus comprises a phototherapy lamp housing and at least one fluorescent lamp mounted in the housing. The lamp comprises a selected phosphor fluorescent source for emitting yellow, orange and/or red wavelengths which provides a fluence in a predetermined desired wavelength band corresponding to the activity absoφtion range of photoactivatable compound, wherein at least about 70% of the unfiltered emission is usable for the PDT.

Also, in accordance with the present invention, an improved method of photodynamic therapy (PDT) is provided for a patient including the steps of administering to a patient a drug that is delivered to a selected skin area and which is activated by light in a wavelength band of a predetermined width. Next, at least one fluorescent lamp is selected comprising a specific phosphor fluorescent source for emitting light in a desired wavelength band of the red, orange and/or yellow spectra corresponding to the photoactivated compound wherein at least 70% of the unfiltered emission is usable for the PDT, and the light is directed onto the treated skin of a patient to effect the photodynamic therapy (PDT). This treatment may take place in single or multiple treatment session.

It is, therefore, an object of the present invention to provide an improved and simplified medical illuminator apparatus for photodynamic therapy (PDT).

It is another object of the present invention to provide an improved medical illuminator apparatus that utilises a low power requirement light source to deliver adequate light energy in a desired wavelength band to a patient in an acceptable period of time. It is another object of the present invention to provide an improved medical illuminator apparatus that utilises a light source that provides light energy in a desired wavelength band to a broad treatment surface while minimising patient time and obviating the necessity of dissipating a high percentage of light energy in the form of heat. It is yet another object of the present invention to provide an improved medical illuminator apparatus that utilises at least one fluorescent lamp light source comprising a selected phosphor fluorescent source so that the lamp will provide a very high proportion of its light emissions in the desired yellow, orange and/or red wavelength band for activation of a selected PDT medicinal compound. It is yet another object of the present invention to provide an improved medical illuminator apparatus that uses a light source that while providing excellent PDT treatment has a relatively low power requirement and that does not require the use of complex filtering to obtain a desired wavelength band for activation of a selected PDT medicinal compound. It is still another object of the present invention to provide an improved medical illuminator apparatus that utilises at least one low-cost and low-power requirement fluorescent lamp that comprises a selected phosphor fluorescent source that is matched to a selected PDT medicinal compound so as to provide a high percentage of light emissions in the desired wavelength band for activation of the PDT drug. Some of the objects of the invention having been stated, other objects will become evident as the description proceeds, when taken in connection with the accompanying drawings described hereinbelow.

Figure 1 is a front view schematic diagram of a representative medical illuminator apparatus for PDT according to the present invention; Figure 2 is a vertical cross-section schematic diagram of the medical illuminator apparatus shown in Figure 1 ;

Figure 3 is a graph of the visible emission spectrum of a fluorescent lamp using Red Phosphor No. 340 fluorescent source; and

Figure 4 is a graph of the absoφtion spectrum of the photoactivated medicinal compound ATMPn.

Referring now to Figures 1 and 2 of the drawings, the present invention provides an improved medical illuminator 10 for activation of selected photoactivated medicinal compounds for photodynamic therapy (PDT). Illuminator 10 includes a housing H having four fluorescent bulbs or lamps 12 mounted in bulb holders 13 and surrounded by (optional) reflectors 14 which serves to direct the emitted light outwardly from fluorescent lamp 12. Optionally, the emitted light may be passed through a UV absorbing acrylic 16 (see Figure 2) in clinical visible light applications to prevent exposure of a patient to actinic wavelengths which tend not to be absorbed by the red phosphor fluorescent source of fluorescent lamps 12. Although four lamps 12 are shown in illuminator 10, one or more lamps 12 may be used (preferably 4-60 lamps 12) depending upon the size of illuminator 10 desired.

It should be appreciated that complex filters are not required in order to obtain a desired light wavelength band that will serve to effectively activate a selected photoactivated medicinal compound. In other words, a light wavelength band that corresponds to a selected photoactivated medicinal compound is caused to be emitted by fluorescent lamps 12 by selecting a suitable phosphor fluorescent source for internal coating of the glass envelopes of lamps 12.

When the use of a fluorescent lamp with a phosphor activating coating for visible light emission in the red, orange and/or yellow spectra was initially conceived, it was believed that a light source or lamp which provided a fluence rate of approximately 20 mW/cm² might be appropriate since indoor tanning beds routinely have UVA fluence rates of about 20 to 40 mW/cm². The concept that a fluorescent lamp using such a phosphor fluorescent source would be satisfactory to activate a photoactivated compound (e.g., ATMPn) was contrary to conventional wisdom in the art that suggested much higher fluence rates would be required for clinical applications of such a medical illuminator apparatus for PDT.

By way of explanation, it should be appreciated that fluorescent lamps are conventionally made for use at three power levels. The standard power level for a 24 inch long bulb or lamp is 20 watts. A high output (HO) lamp of the same length in size requires about 40 watts whereas very high output (VHO) fluorescent lamps require about 80 watts of input power. It was believed that the HO lamp while requiring twice the power would provide only about 50% more light output and that the VHO lamp while requiring twice as much more power than the HO lamp would still only provide an additional 40% more output light power than the HO lamp. Thus, it was recognized that increasing the current through a fluorescent lamp could provide increasing light output, but the increase in light output would probably be offset by a decrease in bulb life and other associated problems. It was also initially believed that by using HO fluorescent lamps that light output levels of 30 mW/cm² and perhaps as much as 60 mW/cm² could be achieved, but it was suφrising to find oniy an output of about 10 mW/cm². When measured, the VHO red, yellow and/or orange spectra phosphor fluorescent source lamps produced only about 12 mW/cm² output and not the 30 mW/cm² light output as anticipated. Apparently this is due to the fact that red photons produced by the red phosphor fluorescent source are only about one-half to one-third as energetic as the short wavelength UV photons emitted by conventional fluorescent source in fluorescent lamps. Thus, due to the low intensities of about 10 - 12 mW/cm² available from fluorescent lamps using red phosphor fluorescent source coatings, it was unexpected and surprising that low intensity fluorescent lamps using red phosphor fluorescent source proved to have a high degree of efficacy for PDT use.

As seen in Figures 1 and 2, a simple and inexpensive source for photodynamic therapy (PDT) applications is shown consisting of lamps 12 that each have the glass envelopes thereof internally coated with a selected red, orange and/or yellow phosphor fluorescent source so as to emit a wavelength band specifically selected to activate certain selected photoactivated PDT drugs.

Medical illuminator apparatus 10 can be constructed with any suitable configuration so that patients may be treated as they lie down, sit up or stand up. Bulbs or lamps 12 can be made in any diameter as a matter of design choice, with the optimum diameter believed to be a T12 conventional ceiling bulb diameter. The length of lamp 12 can be any suitably convenient length from about one foot to about seven feet or greater, although the preferred length is two to six feet. It is contemplated that while straight fluorescent lamps 12 are possibly the least expensive, the glass tubes used in fluorescent lamps 12 can be bent or configured during manufacture into practically any useful shape or configuration as a matter of design choice. As noted hereinabove, due to the energetics of the photons required, HO or VHO fluorescent lamps 12 may be optimum for most long wavelength visible light activated PDT compounds.

It has been discovered that there are many phosphors available for emitting yellow, orange and red visible wavelengths that can be used for the fluorescent source in lamps 12. The phosphors which will be used for the red, orange and/or yellow spectra phosphor fluorescent source are coated by conventional means onto the inside of the glass envelopes of lamps 12 and can be selected and used either individually or in combinations to achieve optimal fluorescent emission for a selected photoactivated drug compound. For example, for AMPTn, (9-acetoxy-2,7,12,17,tetrakis (methoxyethyl)-poφhycene) manufactured by Chemsyn Science Laboratories of Lenexa, Kansas, and disclosed in U.S. Patent No. 5,179,120, which is incorporated herein by reference, it has been discovered that SYLVAN IA brand R340 (Y₂O₄:Eu) and SYLVANIA brand R310 are preferred phosphors for the selected red, orange and/or yellow phosphor fluorescent source, although other phosphors within this spectra band are contemplated as usable within the scope of the present invention. The chemical formula of a number of other representative and selected phosphors for use with the present invention and relevant emissions data with respect thereto is as follows:

SUBSTrrUTE SHEET (RULE 26)

Also, although many different PDT compounds can be used in the present invention, representative photoactivated compounds include 5-aminolevulinic acid (ALA), photofrin, protopoφhyrin, meso-tetrahydroxy-phenyl-chlorine (m-THPC), porphycenes, Sn-etiopuφurin, N-aspartyl chlorine₆ (NPE-6), Z_n-phtalocyanine, benzopoφhyrin, lysyl chlorin P₆ diester (LCP), lysyl chlorin P₆ triester (LCP2) and lysyl chlorin e₆ imide (LCI).

The type of medical illuminator apparatus 10 used for PDT applications will be a function of the size and position of the surface areas requiring the PDT treatment. However, it is contemplated that most apparatus commonly used in PUVA (psoralen UV phototherapy applications) involving fluorescent lamp technology will probably be suitable for use in visible light photodynamic therapy (PDT) applications. These apparatus include light booths, light canopies, light beds, light boxes for irradiation of hands, heads, feet, legs and the like. The apparatus may utilize reflectors 14 such as utilized by apparatus 10 shown in Figures 1 and 2, although such a reflector is not a requirement of medical illuminator apparatus 10 of the invention. A primary advantage of visible light photodynamic therapy (PDT) using medical illuminator apparatus 10 is the inherent safety to patients and clinical technicians. UVA radiation can cause skin cancer, erythema (sunburn) and eye injuries including conjunctivitis and cataracts (corneal opacities). The visible light emitting photodynamic therapy (PDT) apparatus 10 should not produce any risk to patients or clinical technicians due to the low light intensity for single and multiple PDT exposures. Preferably a UV filter, such as acrylic plastic protective cover 16 (see Figure 2) should be used with lamps 12.

The present fluorescent lamp medical illuminator apparatus 10 has a number of inherent advantages including the low cost of the apparatus and fluorescent lamps. While many prior art photodynamic therapy (PDT) lamps and systems presently in use require explosion-proof cases and housings, fluorescent lamp medical illuminator apparatus 10 as contemplated by the present invention does not require any special construction or safety concerns and conventional components can be used, with the exception of the specially ordered and constructed red, orange and/or yellow spectra phosphor fluorescent source fluorescent lamps 12. It is further noted that all required power ballasts and all required fittings are commercially available to make a medical illuminator apparatus 10 according to the present invention.

The fluorescent phosphors can be extremely efficient in providing the wavelength band desired to photoactivate a selected PDT drug compound. For example, the red phosphor SYLVAN IA R340 (Y₂O₄:Eu) provides more than 80% of the visible emission of fluorescent lamps 12 within the desired range of 590 - 650 nm for photoactivation of the representative PDT drug ATMPn compared to all visible emissions of 400 - 800 nm. The use of the red phosphor as the selected fluorescent source for fluorescent lamps 12 obviates the need for additional filtration in order to concentrate the light emissions into a desired wavelength band.

Thus, the present invention contemplates providing a selected red, orange and/or yellow phosphor fluorescent source for fluorescent lamps 12 that will provide fluence in a desired wavelength band that corresponds to the wavelength band for activation of a predetermined photoactivated PDT compound such as ATMPn. The fluorescent bulbs with the selected phosphor fluorescent source emitting light in the red, orange and/or yellow spectra should be relatively inexpensive (e.g., about $10.00 - $15.00 each) and do not require any additional filtering of the light emissions or lens to focus the light. As previously stated, although many photoactivated compounds may be used with the present invention, it is believed that the invention is particularly well suited for photoactivation of a class of compounds known as poφhycenes, and even more particularly for photoactivation of the topically applied photoactivated porphycene compound 9-acetoxy-2,7,12,17-tetrakis(methoxyethyl) poφhycene (ATMPn). The process for synthesizing ATMPn is disclosed in U.S. Pat. No. 5,179,120 which is incoφorated herein by reference. The absorption spectrum of ATMPn is shown in

Figure 4 of the drawings. Based on this absoφtion spectrum, light of any wavelength longer than 500 nanometers and shorter than 700 nanometers might be considered acceptable for activating ATMPn in PDT applications. Other drugs used and proposed for use in PDT applications absorb light at slightly different wavelengths, but illuminator

10 can be utilized to provide optimal wavelengths for many photoactivated drugs (and for all poφhyrin-based light activated drugs or dyes) by simply altering the red phosphor fluorescent source of fluorescent lamps 12 to correspond to and maximize the desired emission wavelengths for the PDT drug or dye selected. Other photoactivated compounds as noted hereinabove include 5-aminolevulinic acid (ALA), photofrin, protopoφhyrin, meso-tetrahydroxy-phenyl-chlorine (m-THPC), Sn- etiopuφurin, N-aspartyl chlorine₆ (NPE-6), Z_n-phtalocyanine, benzopoφhyrin, lysyl chlorin P₆ diester (LCP), lysyl chlorin P₆ triester (LCP2) and lysyl chlorin eβ imide (LCI).

Generally, visible light by itself without the presence of any light activated drug does not pose any health or safety risk for normal individuals. However, recent reports on light absorbed directly into capillaries and the haemoglobin of normal blood indicates that lasers and perhaps other light sources emitting at 577 nanometers can produce undesirable chemicat degradation of haemoglobin with relatively low total exposure. Fortunately, fluorescent lamps 12 with SYLVANIA brand red phosphor No. 340 and/or No. 310 provide a light wavelength band from about 590 to 650 nanometers in width to effectively photoactivate ATMPn for optimum efficacy at minimum risk, as this range falls outside the absorbtion range of haemoglobin.

Of interest, Figure 3 shows the spectrum of light from an HO 24 inch SYLVANIA red phosphor No. 340 (Y₂O₄:Eu) fluorescent lamp and mounted in an 8 bulb HO UV photodynamic therapy housing. The emission was measured in nm increments using an Optronic Laboratories Model 754 Spectra Radiometer. As can be seen in Figure 3, the No. 340 red phosphor fluorescent source has a primary large narrow emission peak at about 610 nm, and at least 70% of the unfiltered emission is usable for the PDT with ATMPn. Table 1 below summarizes the results of the measurements referenced hereinabove. It can be concluded from Table 1 that red light emission from a fluorescent lamp 12 that is suitable for activating the ATMPn photoactivated drug compound and similar PDT drugs can be obtained from unfiltered red emitting fluorescent sources coated by conventional means on the inside surface of the glass envelope of a conventional fluorescent bulb or lamp.

Table 1

As will be appreciated by those skilled in the art, the photoactivatable medicament selected may be delivered from an array of topical dosage forms, including but not limited to, gels, creams, ointments, lotions, and solutions.

As previously stated, the selected photoactivatable compound is administered prior to irradiance. In the case of ATMPn, the preferred amount of drug to be administered is approximately from 0.1 to 100 μg/cm², more preferably from 1 to 60 μg/cm², and most preferably from 10 to 40 μg/cm².

Penetration of the compound into the skin may be enhanced through various techniques known in the field of dermatology. Application of the PDT drug followed by an interval of time prior to irradiance, ranging from several minutes to several hours may increase penetration into the skin. Likewise, occlusion of the surface to be treated with an air and/or light permeable or impermeable cover layer, for example, cellophane or aluminium foil may also prove beneficial. Lastly, selection of permeability enhancing dosage formulations may prove effective.

The fluence of the PDT lamp of the present invention envisaged for photoactivation of the photoactivated compound used in the therapy is preferably in the range of about 5 to 20 mW/cm², more preferably between 7 and 15 mW/cm², most preferably about 10 to 12mw/cm², and particularly preferably 11 mW/cm². Light dosage delivered to the patient per therapeutic session, is preferably from 0.1 to 100 J/cm², more preferably between 1 and 60 J/cm², and most preferably between 4 and 32 J/cm².

SUBSTΠTΠΈ SHEET (RULE 26) The photodynamic therapy itself may take place in a single treatment, or in multiple treatments. The preferred manner of treatment currently envisaged includes one to two treatments per week over a course of between 1 to 25 weeks, more preferably 1 to 20 weeks. Thus, it can be appreciated that the preferred embodiment of illuminator apparatus 10 of the present invention lends itself particularly well to photoactivation of the poφhycene compound ATMPn. However, it is not intended or contemplated that the present invention be limited to use with any specific photoactivated PDT medicinal compound. It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the puφose of illustration only, and not for the puφose of limitation, the invention being defined by the claims.

Claims

1. A medical illuminator apparatus for activation of a predetermined photactivated compound during photodynamic therapy (PDT), comprising:

(a) a phototherapy lamp housing; and

(b) at least one fluorescent lamp mounted in said housing and comprising a selected phosphor fluorescent source for emitting yellow, orange and/or red wavelengths and providing a fluence in a desired wavelength band corresponding to the predetermined photactivated compound wherein at least about 70% of the unfiltered emission is usable for the PDT.

2. A medical illuminator apparatus according to claim 1 wherein the photoactivated compound is selected from the group comprising 5-aminolevuiinic acid (ALA), photofrin, protopoφhyrin, meso-tetrahydroxy-phenyl-chlorine (m-THPC), poφhycenes, Sn- etiopuφurin, N-aspartyl chlorine₆ (NPE-6), Zo-phtalocyanine, benzopoφhyrin, lysyl chlorin P₆ diester (LCP), lysyl chlorin P₆ triester (LCP2) and lysyl chlorin e₆ imide (LCI).

3. A medical illuminator apparatus according to claim 2 wherein the photoactivated compound is 9-acetoxy-2,7,12,17-tetrakis (methoxyethyl)-poφhycene (ATMPn).

4. A medical illuminator apparatus according to any one of claims 1 to 3 wherein the phototherapy lamp housing is selected from the group comprising light booths, light canopies, light beds and light boxes.

5. A medical illuminator apparatus according to any one of claims 1 to 4 including a UN. filter.

6. A medical illuminator apparatus according to any one of claims 1 to 5 wherein the selected phosphor fluorescent source emitting light in the wavelength of the red, orange and/or yellow spectra is selected from the group comprising Y₂O₄:Eu; Y₂O₃:Eu Mg₆As₂On:Mn; Y(PV)O₄:Eu; YVO₆; 3.5MgO:O.5MgF₂GeO₂:Mn; (SrMg)₃(PO₄)₂:Sn CaSiO₃:Pb,Mn; Ca₂(PO₄)₆FCI:Sb₁Mn; LiAIO₂Fe; (Ce,Gd)MgB₅Oι₀:Tb; Y₃AI₅O₁₀.Ce (Ce,Gd,Tb)MgB₅Oι₀:Mn; (Ce.Tb) MgAsnO₁₀; and Mg₄GeO₅F:Mn.

SUBSTrTUTE SHEET (RULE 26)

7. A medical illuminator apparatus according to any one of claims 1 to 6 wherein the selected phosphor fluorescent source is SYLVANIA red phosphor No. 340.

8. A medical illuminator apparatus according to any one of claims 1 to 6 wherein the selected phosphor fluorescent source is SYLVANIA red phosphor No. 310.

9. A medical illuminator apparatus according to any one of claims 1 to 8 wherein the fluence is about 5-20 mW/cm² from the selected phosphor fluorescent source.

10. A medical illuminator apparatus according to claim 9 wherein the fluence is about 10-12 mW/cm² from the selected phosphor fluorescent source.

11. A medical illuminator apparatus according to any one of claims 1 to 10 wherein the desired wavelength band is 590-650nm and greater than 80% of the unfiltered emission of the selected phosphor fluorescent source is within the wavelength band.

12. A medical illuminator apparatus as claimed in any one of claims 1 to 11 for use in a method of photodynamic therapy (PDT) wherein the therapy comprises the following steps:

(a) administering to a patient a PDT drug that is delivered to a selected skin area and which is activated by light in a wavelength band of a predetermined width; and

(b) irradiation of said skin area and consequent activation of said drug by means of light from the medical illuminator apparatus to effect the PDT.

13. A medical illuminator apparatus as claimed in claim 12 wherein the therapy also comprises the step of passing the emitted light through a UN. filter before the irradiation of said skin area.

14. A medical illuminator apparatus as claimed in claim 12 or claim 13 wherein the PDT drug is topically, systemically or intravenously administered.

15. A method of photodynamic therapy (PDT) for a patient comprising the steps:

(a) administering to the patient a PDT drug that is delivered to a selected patient skin area and which is activated by light in a wavelength band of predetermined width; and (b) irradiation of said skin area and consequent activation of said drug by means of light from a medical illuminator apparatus as claimed in any one of claims 1 to 11 to effect the PDT.

16. A method as claimed in claim 15 also comprising the step of passing the emitted light through a UV filter before the irradiation of said skin area.

17. A method as claimed in claim 15 or claim 16 wherein the PDT drug is topically systemically or intravenously administered.

18. A method as claimed in any one of claims 15 to 17 wherein the PDT drug is a poφhycene compound, preferably 9-acetoxy-2,7,12,17-tetrakis(methoxyethyl) poφhycene.