KR20010072307A - Improved method for targeted topical treatment of disease - Google Patents

Abstract

A method and apparatus for topical treatment of diseased tissue comprising topically applying light (24) after topical or systemic application of a PDT agent to the diseased tissue.

Description

IMPROVED METHOD FOR TARGETED TOPICAL TREATMENT OF DISEASE

PDT has been developed to treat tumors and other diseases, with the potential to limit the intrusion of therapeutic interventions and to reduce the potential damage of normal non-disease tissue. Key elements of PDT include the selective application or selective absorption of photosensitive agents to diseased tissue and the site-specific application of activating light. PDT agonists are generally systemic (eg, intravenous or oral) or topical direct application (eg, topical creams, ointments or sprays) to diseased tissue. After administration of the agent (generally between 30 minutes and 72 hours), activating light is applied to the diseased site to locally activate the agent to destroy diseased tissue. Generally, the light is directly irradiated to the site, or optical fiber catheter or similar means is used to deliver the light energy to the internal location.

Most current PDT treatments are based on systemic application of porphyrin-based agents, or topical or systemic application of soralene-based agents. Examples of porphyrin-based agonists include Porpimer Sodium (PHOTOFRIN ™), Hematopophyrin-derivatives (HPD), or SnET2. PHOTOFRIN is one of several agents recently approved by the US Food and Drug Administration. Porphyrin-based agents are generally derived from complex mixtures of natural or synthetic materials. Porphyrin-based agonists are lipophilic. Because of this lipophilic, porphyrin-based agonists tend to accumulate preferentially in some tumors. However, targeting such agents to diseased tissues is still unacceptably low compared to the uptake of normal tissues (ie 2-10 times more absorption in diseased tissues than normal tissues).

In addition, in order to treat deep-seated carcinomas, porphyrin-based agents have been developed primarily with the intention of obtaining agents compatible with activating light having high penetrability. For example, porphyrin-based agonists are generally activated using light at 600-750 nm wavelength, which can penetrate tissue up to a depth of 1 cm or more. In contrast, light with a wavelength below 600 nm will only transmit a depth of less than 1 cm.

However, most porphyrin-based agonists have high dark toxicity. Cancer toxicity refers to cytotoxicity in the absence of activating light. For the treatment of certain tissues, only a small increase in cytotoxicity is required due to the irradiation required for high dose agents. Moreover, systemic removal time, which is the period during which significant concentrations of agent are present in the skin and other external tissues after administration, extends from weeks to months, so that patients are not exposed to bright light or sunlight to avoid severe dermatitis and other complications. Should be. In addition, in the case of systemic administration, a delay of 30 minutes to 72 hours is necessary between photoactivation and agent administration in order to exclude the possibility of immediate treatment of the diseased tissue upon detection of the diseased tissue. In addition, the detection and treatment of gastrointestinal diseases such as Barrett's esophagus requires at least two endoscopy procedures: one procedure is diagnostic and the other subsequent procedure is to treat the diseased tissue with light after administration of the PDT agent.

Since most PDT agents do not have a significant difference between photocytotoxicity and cancer cytotoxicity and most PDT agents have a low preferential concentration ratio, the dosage of the agent should be high. For example, a dosage for treating adult males with PHOTOFRIN may require more than 100 mg of the agent at a cost of more than $ 5,000 of the agent alone. Due to this high dosage, there is a high risk of developing adverse side effects (such as skin phototoxicity) in healthy tissue and may remain for several weeks. In addition, because porphyrin-based agonists are activated with light having a wavelength greater than 600 nm (ie, near infrared (NIR)), methods based on porphyrin + NIR are at high risk of serious complications due to the possibility of tissue penetration of near infrared. Since agents present in healthy tissues besides topical treatment sites are undesirably activated by laser, complications may include perforation of internal structures, such as esophagus, during the treatment of esophageal diseases.

In addition, porphyrin-based PDT agonists result in photo-activated cytotoxicity by converting type-II mechanisms, generally cellular O _2, into cytotoxic oxygen atoms. Since the O ₂ levels of cells can easily be depleted during activation of the Type-II PDT agonists, such agents should be irradiated for a long period of time at relatively low intensity to ensure that sufficient O ₂ levels remain during the photoactive period. For example, when treating Barrett's esophagus with PHOTOFRIN, the light intensity should generally remain below 100-150 mW / cm ² and should be investigated for at least 10-20 minutes during treatment. In addition, studies with type II-agents have shown that a number of practitioners are equally important to prevent any tissue manipulations that could impede blood circulation at the treatment site during light irradiation to prevent potential depletion of available O ₂ . okay. Thus, careful control of the irradiation apparatus and method is key to ensuring that the appropriate light intensity is delivered without affecting the tissue in a manner that affects blood circulation.

The Barrett's esophagus is a perfect example of superficial disease, which is an attractive candidate for PDT, which is inaccessible using conventional endocrine means but is easily accessible using endoscopy. It is a disease that causes long-term reflux of gastric acid, causing inflammation of the esophageal junctional esophagus, causing epithelial cells of the esophagus to proliferate. Patients with Barrett's esophagus are at an increased risk of developing esophageal cancer. The U.S. Food and Drug Administration has approved PDT (PHOTOFRIN ™) that destroys proliferative tissue in Barrett patients. Similar treatments can be used to eliminate esophageal stenosis caused by esophageal cancer.

A common method of treating Barrett's esophagus using PDT is shown in cross section in Figure 1 (a). Esophagus 10 has an inner tissue surface 12 and an outer tissue surface 14. In the example of FIG. 1A, a portion of the esophagus portion 10 is healthy tissue 16 and the other portion is diseased tissue 18. Generally, non-compliant balloons 20 are inserted into the esophagus 10 to stabilize the tissue to be treated. The balloon is filled with gas or liquid to inflate the balloon to a known radius (almost to fill the esophagus) without inflating the esophagus. Due to this swelling, it is possible to limit blood flow to the treatment area, thereby lowering the O ₂ supply during photoactivation. The optical fiber inserted in the center of the balloon 20 acts as a light source 22 to provide a constant light intensity on the surface of the balloon. The outer structure of the balloon 20 may be made of a material that disperses the activating light 24 or is transparent to the activating light.

Light emitted from the surface of the balloon 20 activates the PDT agent in the tissue abutting the balloon (inner tissue surface 12). Since the balloon 20 is noncompliant, it is possible to know the light emission characteristics of the light source 22 and to estimate the light intensity on the surface of the balloon based on the geometric characteristics of the balloon. The fiber diffuser tip is one example of such a light source. However, since the outer surface of the balloon 20 does not completely match the esophagus shape, it is impossible to accurately estimate the light intensity at all points of the outline of the outer tissue representation 12. Moreover, if the light region present on the body tissue surface 12 is not uniform, for example because of the non-uniform light emission characteristics of the light source 22 or the position of the light source 22 in the esophagus 10 is not uniform, treatment may It cannot be made evenly. In extreme cases, such uneven treatment may damage the tissues sufficiently to result in tissue puncture and death of the patient.

As shown in Figure 1 (b), the treatment area 26 can be made by activation of the PDT agonist in the esophageal tissue according to the light irradiation, this treatment area may include the entire diseased tissue in Figure 1 (a) It can extend radially or to a significant distance beyond the excess of diseased tissue area 18. In fact, the use of NIR light for agent activation can form a treatment area that extends a considerable distance from the inner tissue surface 12 of the esophagus 10 to the outer tissue surface 14. This is a result of the very high penetration depth of NIR and the presence of agents at significant systemic concentrations in healthy tissues. In extreme cases, the extension of this treatment area may damage the tissue enough to cause tissue puncture and death in the patient.

Examples of the use of PDTs for the treatment of surface damage present a number of disadvantages of the methods and devices currently used. For example:

(1) Systemic application of agents is expensive because they require high doses of the agent.

(2) Systemic application of agents can make healthy tissue sensitive outside the desired treatment area.

(3) Systemic application of agents can lead to long term skin photosensitivity.

(4) Systemic application of agents requires significant delay between disease diagnosis and disease treatment in order to eliminate agents and reach agents in diseased tissues.

(5) Systemic application of the agent provides PDT performers with limited control of the delivery site and concentration of the agent.

(6) As a result of systemic application of the agent, it is treated unevenly because the agent is distributed unevenly to diseased tissue.

(7) The use of type-II agonists requires slow activation of the long term agonists to prevent O ₂ depletion.

(8) The use of type-II agonists requires careful tissue treatment to prevent blood flow restriction and thus O ₂ depletion during tissue investigation.

(9) In common use with NIR activating light, the use of type-II agonists is too deep for most topical applications and adversely affects the surrounding healthy tissue.

Accordingly, it is an object of the present invention to provide new methods and apparatus for improved application of PDT that reduce treatment costs while increasing the effectiveness and stability of the treatment methods.

Summary of the Invention

The present invention relates to a method and apparatus for topical treatment of diseased tissue, which includes topically or systemically applying a PDT agent to the diseased tissue followed by topical application of light. In general, the method comprises applying a PDT agent to diseased tissue to form a treatment area; Removing excess agent; And activating an agent in the diseased tissue by irradiating the treatment area with light. Here, the light penetrates through the treatment area while minimizing the activation of the agent outside the treatment area.

In a preferred embodiment, Rose Bengal is a PDT agonist.

In a further preferred example, the PDT agent is applied directly only to the treatment area. Or PDT may be applied systemically.

In a further preferred example, in order to prevent activation of the agent in healthy tissue, the depth of activation of the PDT agent is adjusted by selecting the appropriate wavelength of activating light.

In a further preferred embodiment, disease tissue is diagnosed prior to applying the PDT agent.

In another example, instead of using separate diagnostic and therapeutic procedures, damage may be detected and treated in a short time using a single procedure (such as an endoscope).

In another example, the treatment rate is not limited by oxygen-dependent mechanisms.

In another example, heat may be applied to the treatment zone to enhance the activating effect of the agent.

In another example, activating light is delivered through a “balloon” or other delivery device present at the disease site.

In another example, the methods of the present invention can be used to treat gastrointestinal diseases.

The method of the present invention may also be used for the treatment of circulatory vascular diseases.

The invention also relates to a device for topical treatment of a disease.

Accordingly, the present invention relates to methods and apparatus for improving PDT treatment stability and efficacy while improving PDT treatment uniformity while reducing PDT costs for treating Barrett's esophagus and other diseases.

This application is partly pending on US application Ser. No. 08 / 739,801, filed October 30, 1996.

The present invention relates to methods and apparatus for topically treating tissues, particularly diseased tissues, using photodynamic therapy (PDT) and PDT agents. More particularly, the present invention relates to a method and apparatus for topically applying light to a diseased tissue after topical or systemic application of a PDT agent to the diseased tissue.

In describing the preferred example, reference is made to the following drawings.

1 (a) is a fragmentary diagram of the esophagus illustrating a common method for treating Barrett's esophagus using PDT.

Fig. 1 (b) shows the processing area of the method of Fig. 1 (a).

Figure 2 (a) shows an example of the present invention for the treatment of esophageal disease tissue.

2 (b) shows another example of FIG. 2 (a).

Fig. 2 (c) shows another further example of Fig. 2 (a).

3 (a) is another example of the present invention for treating circulatory vascular disease.

Figure 3 (b) is another example of Figure 3 (a) that directly applies PDT to diseased tissue.

The methods and devices of the present invention can be applied to improved methods of various skin diseases such as psoriasis or skin cancer, and can be applied to diseased tissues within the body, such as diseases of the digestive or respiratory tract. The invention can also be used for the treatment of other anatomical sites, including intraperitoneal, intrathoracic, intracardiac, intracranial, and reproductive tracts.

In general, the method of the present invention includes one or more of the following steps. The disease is first diagnosed, for example, by biopsy or by measuring the autofluorescence properties of diseased tissue or by detecting selective absorption of an indicator, such as a fluorescent dye or PDT agonist, into the disease site. Thereafter, a topical or systemic preparation of the desired PDT agent is applied to the diseased site in sufficient amount to cover, spray or saturate the diseased tissue. After some time for the agent to be coated, sprayed or activated in the diseased tissue, the excess agent is removed or washed away from the diseased area and a substantially uniform light area is applied to the diseased area. Activate the agent in the tissue.

For the treatment of superficial diseased tissue, light wavelengths are chosen to allow light to pass through the diseased tissue while minimizing light transmission to the healthy tissue beneath the diseased tissue. For example, visible light in the 400-600 nm region may be used to transmit light thinly up to several milliliters. The use of such light provides an activating effect of the agent in surface disease tissue while minimizing the possibility of lethal photosensitization of the underlying tissue. Preferably, laser light is used. Deliver using an optical fiber catheter. Or light is provided by direct irradiation. Other light source forms and delivery devices include optical fiber bundles, hollow-core optical waveguides, and liquid-filled waveguides. Still other light sources include light emitting diodes, micro-lasers, short or continuous wavelength lasers or lamps that produce activating light, and continuous or pulsed lasers or lamps. Single-photon or two-photon excitation methods can also be used to activate the agents. A more detailed description of this excitation method is described in US application Ser. No. 08 / 739,801 filed October 30, 1996, which is incorporated herein by reference.

Moreover, the order and time of treatment of the agent and the light also vary. For example, treatment regimens of light and agents can be repeated one or more times to remove residual diseased tissue. In addition, in some applications it is advantageous to increase the delay between agent application and light treatment. In addition, immediately after the diagnosis step, the step of applying the PDT agent, the step of removing the excess agent, and the step of applying the light are performed to perform the diagnosis and treatment method in a single step. When PDT agonist uptake is used for the diagnosis or detection of diseased tissue, an agent activation step may be performed immediately after the diagnostic step. Or there may be an infinite delay between diagnosis and PDT treatment.

Preferably, los bengal is inexpensive, non-toxic, stable to human use, has a fairly intrinsic lipophilic character, and exhibits both type-I and type-II reactions, thus providing a type-I oxygen-ratio Los Bengal can be used as a PDT or photosensitive agent because it can be activated as a dependent mechanism and has strong photocytotoxicity by photoactivation in the 500-600 nm range. Due to Los Bengal's O ₂ -independent reaction, Rose Bengal is compatible with high intensity photoactivation and can reduce processing time compared to porphyrin-based agents. More specifically, rose bengal can be optimally activated with light of 500-600 nm wavelength sufficient to activate surface diseased tissue while substantially preventing the activation of underlying healthy tissue. An example of such a PDT agent is a solution formulated with rose bengal with a suitable lipophilic delivery carrier such as 1-octanol or liposomes.

Alternatively, other PDT agents can be used, including type-I or type-II agents. Examples of such standard PDT agonists include soralene derivatives, porphyrins and hematopophyrin derivatives; Crawlin derivatives; Phthalocyanine derivatives; Rhodamine derivatives; Coumarin derivatives; Benzophenoxazine derivatives; Clopromazine and clopromazine derivatives; Chlorophyll and benteriochlorophyll derivatives; Pheophorbide a (Pheo a); Merocyanine 540 (MC 540); Vitamin D; 5-amino-lavulinic acid (ALA); Photoacids; Pheophorbide-a (Ph-a); Phenoxazine nil blue derivatives including various phonoxazine dyes; PHOTOFRIN; Benzoporphyrin derivative monoacid; SnET2; And rutex. The inventors of the present invention believe that all existing and future PDT agents can be used in the methods and devices of the present invention.

In addition, the present invention is not limited to the use of PDT agents. Instead, one or more PDT agents can be used during the treatment regimen.

In a further example, the PDT agent used in the present invention may comprise one or more targeting moieties. Examples of such targeting moieties include DNA, RNA, amino acids, proteins, antibodies, ligands, heptenes, carbohydrate receptors or complex agents, lipid receptors or complex agents, protein receptors or complex agents, chelators and encapsulation carriers. Such targeting moieties may be used to enhance delivery selectivity of the agent to diseased tissue and may be associated with, or attached to, the photosensitized PDT agent, where the PDT agent is encapsulated in a carrier comprising the targeting moiety. Function, wherein the PDT agent is covalently bound to the target moiety.

In a further preferred embodiment, the PDT agent may be applied directly to the diseased tissue. Topical direct application has many advantages. Specifically, by topical direct application, the targeting of agents specific to diseased tissue is improved, the essential potential between agent administration and photoactivation is reduced, thereby reducing treatment cycles and substantially eliminating the possibility of systemic photosensitization. Can reduce the agent consumption and reduce the likelihood of side effects from exposure to the agent. Preferably, the agent is applied by topical spraying or washing. After a short accumulation period (typically not exceeding 30 minutes), excess agent is removed from the tissue surface by washing with a liquid such as water or saline. After this washing, 400-600 nm visible light is irradiated to the diseased tissue to activate the agent remaining in the diseased tissue. Optionally, the light may be applied as mentioned above.

Alternatively, PDT agonists may be applied systemically. For example, such an application can be administered systemically by intravenous or parenteral administration (eg, as a tablet or liquid formulation of a PDT agent).

In a further example, heat may be applied to the treatment zone to enhance PDT efficacy through solidus temperatures. For example, heat can be applied by using a liquid heated to a light emitting balloon, using a transparent heating pad located between the light source and the tissue, or irradiating infrared energy to the treatment area at the same time.

Some embodiments of the present invention are shown in cross-section in FIGS. 2 (a), 2 (b), and 2 (c).

Figure 2 (a) is an example for the treatment of esophageal disease tissue using a non-compliant balloon 20 irradiation apparatus. First, the processing area 30 is determined. Such confirmation is performed by endoscopy of the esophagus and visual or microscopic examination of diseased tissue. Such identification includes detection of tissue changes or indicators of other gross diseases, changes in autofluorescence, or absorption into diseased tissue of PDT agents or other agents. The agent can be applied by direct injection, for example using systemic application, more preferably using a nozzle or other means at the end of the endoscope. Excess agent is removed, for example by natural systemic removal or by rinsing with liquid.

A transparent, non-compliant balloon device 20 is inserted into the esophagus to widen the treatment area 30. The non-compliant balloon 20 is filled with a gas or liquid at a predetermined pressure to have a predetermined radius. A light source 22 located along the central axis of the balloon, such as an optical fiber diffuser, is used to uniformly and radially transmit visible light 24 through the balloon wall to the processing area.

In addition, the balloon 20 is filled with a dilute solution of a dispersing medium, for example, internal lipids, to improve the uniformity of light intensity transmitted from the surface of the balloon. In addition, the balloon 20 may include or consist of a material for dispersing the light 24 transmitted to the balloon surface, thereby improving the uniformity of the light intensity transmitted to the balloon surface. Examples of such materials include latex; Polymers comprising special dispersion materials; Or naturally translucent materials such as polymers having roughened surfaces.

In the example of FIG. 2 (a), the intensity of the light source 22 is adjusted to a predetermined level for a predetermined period based on the filling radius of the non-compliant balloon 20 and the light intensity and light quantity of the balloon surface.

Another example of this embodiment is illustrated in cross-section in FIG. 2 (b), and an expanded non-compliant balloon 40 is used to treat esophageal disease tissue. In this example, after identifying the diseased tissue, the PDT agent is applied to the identified diseased tissue. Excess agent is removed at this site.

Thereafter, a transparent non-compliant balloon device 40 is inserted into the esophagus and fills the treatment area 30. Filling the non-compliant balloon 40 with gas or liquid substantially expands and weakens the esophagus and removes wrinkles on the esophagus surface to provide a more uniform tissue surface 12 for light irradiation. The filling pressure is measured to obtain the radius of the filled balloon. Thereafter, the visible light 4 is uniformly transmitted radially and uniformly to the treatment area through the balloon wall using a light source 22 located along the central axis of the balloon, such as an optical fiber diffuser.

Additionally, the balloon 40 is filled with a dilute solution of a dispersing medium, such as internal lipids, to improve the uniformity of the light intensity delivered to the balloon surface. Additionally, the balloon 40 includes or consists of a material that disperses the light 24 transmitted to the balloon surface. Examples of such materials include natural translucent materials such as latex; In particular polymers comprising dispersants; Or a polymer having a roughened surface.

The pressure used to fill the balloon is measured to determine the radius of the filled balloon, and a level selected based on the operating radius of the non-compliant balloon 40 filled to deliver the desired light intensity and intensity on the balloon surface. The intensity of the light source. In another example, it is desirable to use sufficient pressure to minimize wrinkles in the treated organ area without expanding the organ to prevent potential stenosis or other non-specific inflammation of the esophageal tissue.

An additional example of this embodiment is illustrated in the cross-sectional form of FIG. 2 (c), whereby a compliant balloon is used to treat esophageal disease tissue. In this example, after identifying the diseased tissue, the PDT agent is applied to the identified diseased tissue. Excess agent is removed from the site.

Then a transparent compliant balloon device 50 is inserted into the esophagus to fill the treatment area 30. The compliant balloon 50 is filled with gas or liquid to fill, dilate or slightly expand the esophagus and eliminate uneven contact between the esophagus surface and the balloon to provide a uniform tissue surface for light irradiation. The filling pressure is measured to obtain an approximate radius of the filled balloon. Thereafter, a light source 22 located along the central axis of the balloon, such as an optical fiber diffuser, is used to uniformly and radially transmit visible light 24 through the wall of the balloon to the treatment area.

Alternatively, the balloon 50 is filled with a dilute medium, such as a dilute solution of internal lipids, to increase the uniformity of the light intensity delivered to the balloon surface. In addition, the balloon 50 may include or consist of a material that disperses the light 245 to be delivered to the balloon surface. Examples of such materials include natural translucent materials such as latex; A polymer comprising a specific dispersion; Or polymers having roughened surfaces.

The operating radius of the filled balloon is obtained by measuring the pressure used to fill the balloon. Thus, in this example, the intensity of the light source is manipulated to a selected level based on the operating radius of the compliant balloon 50 filled to deliver the desired light intensity and amount of light to the balloon surface. Preferably, in another example, sufficient pressure is used to minimize wrinkles in the treated esophageal region without dilatating the esophagus (to prevent potential stenosis or other nonspecific inflammation of the esophageal tissue).

Preferred embodiments of the present invention are illustrated in FIGS. 3A and 3B for the treatment of diseases of the circulatory vessels (eg arterial or venous flocs).

In the example of FIG. 3 (a), the photosensitive agent is applied parenterally via intravenous injection. The agent accumulates in the diseased tissue of the vessel wall 60 to form the treatment area 62. The agent was selected based on the concentration preferential to the disease agent present in the desired treatment area. After a short accumulation period, light 64 was applied to the diseased site to activate the agent bound to the diseased substance. The application of this light is carried out using an optical fiber catheter or similar means having focusing, collimation or diffusion ends to spatially control the light transmission. The optical fiber catheter 66 delivers the light 64 directly to the treatment area 62 to enable local application of light. In order to minimize the potential for light transmission to the underlying healthy tissue, it is desirable to use visible light in the spectral region 400-600 nm which provides a thin thickness transmission region to a depth of several millimeters or less. The use of such light activates agents in surface disease agents but simultaneously minimizes the potential for lethal photosensitization of underlying tissues.

Alternatively, as illustrated in FIG. 3B, the photosensitive agent may be administered by applying the agent directly to the disease substance in the treatment region 62. Agent delivery devices 68, such as capillary tubes, attached to the optical fiber catheter 60 and ending near the end thereof, which are used to deliver a small amount, i. The agent can be easily administered through. Alternatively, the delivery device 68 is separate from the optical fiber catheter 66 to facilitate independent positioning relative to the distal end of the agent delivery device 68 and the optical fiber catheter 66. In another example, after a small accumulation period after delivering a small amount of photosensitive agent to the diseased substance in the treatment area 62, light 64 is applied to the diseased portion to activate the agent bound to the diseased substance.

Preferably, in these embodiments, rose bengal is used as the photosensitive agent. Light in the 500 nm-600 nm range optimally activates los bengal, and this wavelength is sufficient for the activation of surface disease agents while substantially preventing the risk of activation of underlying health tissue. In addition, this agent is compatible with high intensity activating light, which can substantially reduce the treatment time required for other agents, such as type-II PDT agents.

This detailed description is not intended to limit the application of the invention as defined in the following claims, which are presented for illustrative purposes only.

New claims that are preferred and protected by patent rights are set forth in the appended claims.

Claims (67)

Applying a PDT agent to diseased tissue to form a treatment area; Removing excess agent; Applying light to the treatment zone to activate an agent bound to the tissue, wherein the light penetrates the treatment zone but minimizes activation of the agent present outside the treatment zone. The method of claim 1, wherein the light is a wavelength that transmits through the treatment area while minimizing transmission of surrounding tissue. The method of claim 2, wherein the wavelength of light is about 400-600 nm. The method of claim 1, wherein the light activates the agent with single photon excitation. The method of claim 1, wherein the light activates the agent with two photon excitation. The method of claim 1, wherein applying the PDT agent, removing excess agent, and applying light one or more times. The method of claim 1, further comprising diagnosing the diseased tissue prior to applying the PDT agent. 8. The method of claim 7, wherein the diagnosing step comprises using autofluorescence properties of the diseased tissue. 8. The method of claim 7, wherein said diagnosing comprises detecting selective absorption of the indicator. 10. The method of claim 9, wherein the indicator is selected from the group consisting of fluorescent dyes and PDT agents. 8. The method of claim 7, wherein immediately after the diagnosis step, applying the PDT agent, removing the excess agent, and applying light, thereby performing the diagnosis and treatment in a single procedure. 8. The method of claim 7, wherein there is a delay between the diagnosis step and the step of applying the PDT agent. The method of claim 1, wherein the PDT agent is los bengal. The method of claim 13, wherein the light has a wavelength in the range of about 500-600 nm. The method of claim 1, wherein at least one PDT agent is applied to the diseased tissue. The method of claim 1, wherein the PDT agent comprises a targeting moiety. The method of claim 16, wherein the targeting moiety comprises a DNA, RNA, amino acid, protein, antibody, ligand, heptene, carbohydrate receptor or complexing agent, lipid receptor or complex agent, protein receptor or complex agent, chelator, and The method is selected from the group consisting of encapsulated carriers. The method of claim 1, wherein the PDT agent is applied directly to the diseased tissue. The method of claim 1, wherein said PDT agent is applied systemically. The method of claim 1, wherein the excess agent is removed by natural systemic clearance. The method of claim 1 wherein the excess agent is removed by washing with a liquid. 2. The method of claim 1, further comprising applying heat to the treatment zone to increase activation of the agent. The method of claim 1 wherein the light is applied through a balloon catheter device. The method of claim 23, wherein the balloon catheter device is non-compliant. 25. The method of claim 24, wherein the non-compliant balloon catheter device is inflated to substantially expand the treatment area. The method of claim 23, wherein the balloon catheter is compliant. The method of claim 23, wherein the balloon catheter is filled with a dispersion medium. 24. The method of claim 23, wherein the balloon catheter comprises a material that scatters light. The method of claim 1 wherein the light is applied by direct irradiation. 2. The light beam of claim 1, wherein the light is a bundle of optical fibers, hollow-core optical waveguides, liquid filled waveguides, light emitting diodes, micro-lasers, short wavelength lasers, continuous lasers, lamps, continuous wavelength lasers, and pulses. Method applied to a light source selected from the group consisting of lasers. Applying a PDT agent to diseased tissue of circulatory vessels to form a treatment area; Applying light to the treatment zone to activate the agent bound to the tissue, wherein the light penetrates the treatment zone but minimizes activation of the agent outside the treatment zone, How to treat diseases of the circulatory vessels. 32. The method of claim 31, wherein said PDT agent is applied parenterally. 32. The method of claim 31, wherein said PDT agent is applied intravenously. 32. The method of claim 31 wherein the light is applied to an optical fiber catheter. 32. The method of claim 31, wherein the light has a wavelength in the range of about 400-600 nm. 32. The method of claim 31, wherein said PDT agent is applied directly to diseased tissue. The method of claim 36, wherein said agent is applied via a capillary tube. 32. The method of claim 31, wherein said PDT agent is rose bengal. The method of claim 38, wherein the light has a wavelength in the range of about 500-600 nm. PDT agents to be applied to diseased tissue to form treatment zones; Means for removing excess agent; And A light source of light for activating the PDT agent in the treatment zone, Wherein the light can penetrate the diseased tissue but minimize activation of an agent outside the diseased tissue. 41. The apparatus of claim 40, wherein the light has a wavelength that transmits to the treatment area while minimizing further transmission to surrounding tissue. 42. The apparatus of claim 41 wherein the wavelength ranges from about 400-600 nm. 41. The device of claim 40, wherein the light activates the agent with single photon excitation. 41. The device of claim 40, wherein the light activates the agent with two photon excitation. 41. The device of claim 40, comprising an indicator for diagnosing the diseased tissue by detecting selective uptake of the indicator. 46. The device of claim 45, wherein said indicator is selected from the group consisting of fluorescent dyes and PDT agents. 41. The device of claim 40, wherein the PDT agent is rose bengal. 48. The device of claim 47, wherein the light has a wavelength in the range of about 500-600 nm. 41. The device of claim 40, further comprising applying one or more PDT agents to the diseased tissue. 41. The device of claim 40, wherein the PDT agent comprises a targeting moiety. 51. The method of claim 50, wherein the targeting moiety consists of DNA, RNA, amino acids, proteins, antibodies, ligands, heptenes, carbohydrate receptors or complex agents, lipid receptors or complex agents, protein receptors or complex agents, chelators, and encapsulation carriers. Device selected from the military. 41. The device of claim 40, wherein the PDT agent is applied directly to diseased tissue. 41. The device of claim 40, wherein the PDT agent is applied systemically. 41. The device of claim 40, further comprising applying heat to the treatment zone to increase activation of the agent. 55. The device of claim 54, wherein said heat is applied as a heated liquid in a balloon catheter device. The apparatus of claim 54 wherein the heat is applied with a transparent heating pat. 41. The device of claim 40, wherein light is applied through the balloon catheter device. 59. The device of claim 57, wherein the balloon catheter device is non-compliant. 59. The apparatus of claim 58, wherein the non-compliant balloon catheter device is inflated to substantially expand the treatment area. 59. The apparatus of claim 57, wherein the balloon catheter is compliant. 59. The device of claim 57, wherein the balloon catheter is filled with a dispersion medium. 59. The device of claim 57, wherein the balloon catheter comprises a material that disperses light. 41. The apparatus of claim 40 wherein the light is applied by direct irradiation. 41. The group of claim 40, wherein the light consists of a fiber bundle, a hollow-core optical waveguide, a liquid-filled waveguide, a light emitting diode, a micro-laser, a short wavelength laser, a continuous laser, a lamp, a continuous wavelength laser, and a pulsed laser. Applied by the light source selected in. The method of claim 1, wherein the PDT agent is one or more standard PDT agents. 32. The method of claim 31, wherein said PDT agent is one or more standard PDT agents. The device of claim 40, wherein the PDT agent is one or more standard PDT agents.