IL308772A - Photodynamic therapy of a cancerous tumor using illumination from within the organ - Google Patents

Description

PHOTODYNAMIC THERAPY OF TUMOR BY INTRA-ORGAN ILLUMINATION TECHNOLOGICAL FIELD The presently disclosed subject matter is in the general field of photodynamic therapy (PDT) and more particularly in the field of vascular-targeted photodynamic therapy (VTP). PRIOR ART References considered to be relevant as background to the presently disclosed subject matter are listed below: - Housami et al., Indian J Urol. 25(1):105-109, 20- Kershen et. al, J. Urol. 168: 121-5, 2002 - Lilge L, et al. J Biomed Opt. 25: 1, 20- Marijnissen JPA, et al. Photochem Photobiol. 58(1): 92-99, 19- Filonenko EV, et al. Photodiagnosis and Photodynamic Therapy. 16: 106-109, 20- Waidelich R, et al. Urology. 61(2): 332-337, 2003 - Houshi et al., Int J Urol. 4(5):493-499, 19Acknowledgement of the above references herein is not to be inferred as meaning that these are in any way relevant to the patentability of the presently disclosed subject matter.

BACKGROUND Approximately 75% of patients with bladder cancer have a non-muscle invasive bladder cancer (NMIBC) form of the disease. In such patients, the goal is to prevent progression and limit recurrence. The common treatment involves non-systemic intravesical chemotherapy into the lumen of the bladder. Unfortunately, NMIBC frequently recurs. Currently the standard of care for patients with a high risk of recurrence of NMIBC is intravesical administration of Bacillus Calmette-Guerin (BCG). BCG can also be given as a maintenance therapy for patients with intermediate and high risk NMIBC. However, management of the ‘BCG-refractory’ patient is the greatest challenge in the field as the lifestyle-altering radical cystectomy is currently the most common option. Photodynamic therapy (PDT) is a form of phototherapy involving a photosensitizer drug and light to elicit cell death. In classical PDT, photosensitizer drugs administered to a subject may preferentially accumulate in the tumor tissues, because of the enhanced permeabilization and retention (EPR) effect and thereafter undergo further accumulation in the rapidly proliferating cancer cells. Photosensitizer activation by application of light at specific wavelengths limited to the tumor site, generates short-living reactive oxygen species (ROS) by interaction with local oxygen resulting in apoptosis or necrosis of the cancer cells. Most common sensitizers are activated at the time of preferential accumulation in the tumor tissue and uptake by the cancer cells. Furthermore, the active ROS generated by these sensitizers is singlet oxygen, which oxidizes proteins and lipids essential to cell survival (Type II mechanism), thereby leading to cell death by apoptosis or necrosis and consequently tumor non-thermal ablation. For at least 30 years, there have been attempts to use PDT to treat bladder cancer . One of the major obstacles has been to achieve whole bladder wall uniform illumination from a single diffuser light source. As the bladder is an irregularly shaped cavity with varying optical properties (Lilge L, et al. J Biomed Opt. 2020;25(06):1), the light at each location on the bladder wall is highly variable as it is a combination of both the incident light from the light source and the scattered light in the bladder, which can be at least up to a factor of six than the incident light (Marijnissen JPA, et al. Photochem Photobiol. 1993;58(1):92-99). Attempts to equalize the light intensity have been made by inflating the bladder to make it round, using a cystoscope (Filonenko EV, et al. Photodiagnosis and Photodynamic Therapy. 2016;16:106-109) or ultrasound placement (Waidelich R, et al. Urology. 2003;61(2):332-337) of the fiber diffuser source, using multiple light intensity probes on the bladder surface to position the light source to achieve uniform intensity (Lilge L, et al. J Biomed Opt. 2020;25(06):1), or using balloons to diffuse the light and/or center the fiber (Waidelich R, et al. Urology. 2003;61(2):332-337). As evident by the lack of advancement to clinical use, these methods have not succeeded. Thus, a safe and straightforward procedure for full bladder wall illumination is desired.

Vascular-targeted photodynamic therapy (VTP) is a photodynamic therapeutic technique whereby photosensitization is applied shortly after intravenous (IV) administration of the photosensitizer, while still in the circulation to a large extent. Some VTP type drugs such as Redaporfin or Visudyne (Verteporfin) are delivered in liposomes and rapidly taken up by the vascular endothelial cells. Subsequent tumor illumination causes endothelial cell death, vascular thrombosis, and flow arrest. In contrast, bacteriochlorophyll derivatives (Bchl-D), such as Padeliporfin (also known by its code name WST11), are water soluble VTP drugs that non-covalently bind to serum albumin and are neither taken up by the tumor endothelium, nor extravasate until clearance. Illumination of the tumor vascular bed by light at the range of red to near infrared-light, delivered through an optical fiber, typically connected to a laser, activates the circulating Bchl-D. The activated Bchl-D generates hydroxyl and superoxide radicals (Type I mechanism) followed by local hypoxia and endogenous nitric oxide generation. A cascade of biological processes is initiated resulting in tumor vascular arrest followed by destruction and cell killing that culminates in a coagulative necrosis of the tumor tissue, while normal blood vessels, particularly those larger than 40 microns in diameter, can be preserved. The endothelial and cancer cell necrosis is followed by activation of anti-tumor immunity that may complete the eradication of any of remaining the illuminated tumor. WST11-VTP has been recently termed Padeliporfin VTP.

GENERAL DESCRIPTION This disclosure concerns photodynamic therapy (PDT) of a target tissue. Two aspects are described below. One of these aspects concerns PDT treatment of a body cavity, including, but not limited to a luminal organ, to be referred herein as the "cavity treatment aspect". The other aspect concerns a PDT treatment of a target organ or tissue comprising feeding the PDT drug into a feeder artery of the target organ or tissue, to be referred to herein as the "feeding aspect". These aspects will be separately described below. However, as will also be noted below, the feeding of the PDT, as provided by the feeding aspect, is an option by some embodiments of the cavity treatment aspect; in other words, by such embodiments, the PDT is fed into the feeding artery of the treated luminal organ. Similarly, by some embodiments of the feeding aspect it may be applied in the treatment according to the cavity treatment aspect.

Various embodiments for each of the aspects will also be described below. Embodiments described in connection with the cavity treatment aspect may also be applicable, mutatis mutandis, in the feeding aspect; and vice versa. The section heads in the general description are provided for convenience and the embodiments described in one section should not be construed as being applicable to such section only. The term "PDT" as used herein is meant to denote all these types of PDT, VTP being a specific example. Also, in the description below, reference is made, at times, to PDT, which is one specific embodiment of this disclosure, it being understood that it is not meant to be limiting of the disclosure, which applies to the full scope as noted above. The terms "PDT drug", "PDT-effective drug", "photosensitizer drug", or the like, are meant to denote one or a combination of agents that are administered to the subject and that can be activated by light to cause them to generate a chemically reactive species, typically, but not exclusively, a reactive oxygen species. The terms "PDT-effective light", "photosensitizing-effective light" or the like, are meant to denote light that has the effect of activating the PDT-effective drug. The term "about" denotes a quantity which may deviate (namely being higher or lower) by up to 10%, 15%, 20%, 25% or even 30%, from the stated quantity. For example, about 10 should be understood to be in the range of 9-11, 8.5-11.5, 8-12, 7.5-12.5, or even 7-13. Even where value are given without the "about" qualification, these should be construed to mean to be about the indicated value, namely the value with a possible deviation as noted in this paragraph. Cavity treatment aspect By one embodiment the target tissue is the wall of a luminal organ, e.g. for the purpose of ablating or otherwise damaging a tumor in the walls of such luminal organ or beyond the walls of the organ. The PDT is carried out from within the lumen in the target organ and substantially covers most of or the entire inner surface of the organ’s lumen. Non-limiting examples of luminal target organs include the bladder, gall bladder, intestines (e.g., the colon), esophagus, and biliary duct. By one embodiment of this disclosure, the PDT method is a vascular-targeted photodynamic therapy (VTP). Other exemplary embodiments are immune photo-activated cancer therapy (Padeliporfin VTP) and a PDT that targets a photosensitizer drug absorbed by the cancer cells.

It was realized, in accordance with this disclosure that PDT may be a viable treatment option of a luminal organ. It was specifically realized according to one embodiment of this disclosure, that whole bladder photodynamic therapy could be a viable option for BCG refractory or resistant patients, providing a minimally invasive tool for bladder tumor(s) ablation while preventing or at least delaying surgery. Specifically, Padeliporfin vascular targeted phototherapy (VTP) may be a specific PDT option, by an embodiment of this disclosure. Unlike other PDT treatments known in the art, VTP attacks the blood vessels directly as the drug (Padeliporfin) does not penetrate the tissues, and, if properly administered, does not ablate muscle, and, hence, minimally affect the luminal organ. It was further realized, in accordance with this disclosure, that proper whole lumen illumination, without causing harm to the luminal walls could be achieved by performing the PDT by means of a balloon catheter made of transparent or translucent material, and irradiating the drug sensitizing-effective light from within the inflatable balloon section thereof while it is inflated. The inflation of the balloon portion of the balloon catheter may be affected using a pressurized liquid, e.g. saline or saline mixed with a contrast agent. In this manner, the irradiated light would reach the luminal walls in a substantially even manner ensuring that a substantially large portion of the lumen is illuminated. Furthermore, the liquid-filled inflated balloon ensures that the placing of the light diffuser, which is at the terminal portion of the light probe (described below) at a sufficient distance from the luminal walls to avoid damage which may otherwise occur as a consequence of proximity between the diffuser and the walls. Provided by this aspect of the disclosure are systems and methods for use in PDT therapy of a luminal organ. Provided by one aspect of this disclosure is a catheter system, comprising an optical probe and a balloon catheter, each of which axially extends between respective proximal and distal ends. The optical probe is optically couplable at its proximal end to a light source; has a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from said light diffuser in a non-axial direction, e.g., a substantial portion thereof being radiated in the radial direction; and has one or more probe-associated imaging markers at said distal end portion. The balloon catheter has (i) a proximal end that is fluidically couplable to a source of pressurized liquid, (ii) an inflatable balloon section at its distal end portion capable of inflation to occupy a substantial portion of an endoluminal cavity, (iii) a working channel capable of accommodating the optical probe introduced through the proximal end in a leakage proof manner (namely, to prevent back-flow, e.g., a Touhy Burst adapter) and being configured for fixing the optical probe in position with respect to said inflatable balloon while in an inflated state, and (iv) one or more balloon-associated imaging markers associated with the inflatable balloon section. The embodiments that are described below may each be applicable in other aspects of this disclosure. For example, the above defined system and any of its embodiments described below, are all usable in the below-described method. In some embodiments, the system comprises at least two probe-associated imaging markers flanking the light-diffusing section of said probe. The system may also comprise two balloon-associated imaging markers associated with said inflatable balloon section. In some embodiments of the system, the balloon-associated and the probe-associated imaging markers are X-ray markers. The balloon-associated and the probe- associated imaging markers may be annular metallic (e.g., gold) elements. In some embodiments of the system, the optical probe is axially displaceable within the catheter working channel until the light diffusion section is within the inflatable balloon section. In some embodiments of the system, the inflatable balloon is configured for a high inflation to deflation ratio. Specifically, the ratio between the diameter of the inflatable balloon in the inflated state to the diameter in a deflated state may be at least 5:1, optionally 7:1 or 10:1. In some embodiments of the system, the pressurized liquid is free of light-scattering elements. The liquid may be water or saline, optionally comprising an X-ray contrast agent; for example the saline may comprise between about 1% and about 10% (v/v) X-ray contrast material such as a diatrizoate sodium solution, marketed by Amersham Health Inc., and known by its tradename Hypaque™ or an iohexol solution marketed by GE Helathcare under the tradename Omnipaque™. In some embodiments, the system may be intended for use in photodynamic therapy (PDT). The PDT may be vascular targeted phototherapy (VTP). In some embodiments of the system, the balloon catheter is configured for insertion through a body orifice leading to an endoluminal cavity, and the inflatable balloon section is configured, when in said deflated state, to occupy substantially a large portion of the volume of said cavity. The endoluminal cavity may be the bladder or a portion of the gastrointestinal tract, e.g., colon, esophagus, biliary duct, gall bladder. In some embodiments of the system, an inner face of the working channel, at least at a distal end portion thereof has a surface structure that is configured for fixing said optical probe in position with respect to the balloon catheter in said inflatable state. The inner face may be smooth, serrated, dented, rough, having small inward projections or undulations or otherwise uneven. At the inflated state, the pressurized fluid within the inflated balloon, presses also the sections of the balloon catheter that lie within the confines of the inflated balloon, such pressure working, among others, to slightly constrict such sections and thereby immobilize the optical probe, particularly where such sections have an uneven surface. In the case of a smooth surface, the optical probe may be held is place by advancing the probe into the distal structure and locking the optical probe at the entrance to the balloon proximal surface using a seal, such as a Tuohy Borst Adapter. The distal section of the balloon catheter is typically configured to permit contact between the light diffuser and the liquid filling the balloon in its inflated state. The liquid has a large heat capacity and thus serves as a heat sink cooling the light diffuser which would otherwise overheat. Such contact may be achieved by detaching a terminal section of the balloon catheter’s working channel from more proximal sections or providing openings in the balloon catheter’s working channel wall in a region thereof intended to encompass the light diffuser after inflating the balloon section and during light irradiation. The openings should be such so as to permit efficient convection flow of the liquid within the working channel surrounding the diffuser and the surrounding liquids that fill the balloon. The light diffuser, once properly positioned, e.g. through imaging and use of the imaging markers for proper positioning, should be maintained in this position throughout the light irradiation treatment, this being achievable by the structure of the inner face of the working channel as noted above or by locking the optical probe on the proximal end. The opening in the walls of the balloon catheter’s working channel may be in the form of longitudinal slits, holes, pores, etc. or in other embodiments completely detached. In some embodiments, the system further comprises a source of light emitting light at a wavelength in the near infrared wavelength range, e.g. about 753 nm, and couplable to the proximal end of said light probe. The system may have an output power of above about 0.5, 1, 2, 5, 7, 10, 20, 30, 40 or up to 50 Watts.

In some embodiments, the system may be for use in a vascular-targeted photodynamic therapy (VTP) that comprises a catheter injection system according to the feeding aspect, described below, wherein a distal portion thereof is configured for insertion into a feeder artery of the target tissue, and comprises a VTP drug injection device coupled to a proximal end of the delivery catheter and for forcing VTP-type drug into the catheter, the VTP being fed into said feeding artery resulting in blood concentrations suitable for VTP procedures in the target tissue. Provided is also a method, for photodynamic therapy (PDT) of a target site in an endoluminal cavity of a subject. The method comprises, in the stated or any other suitable order, the following: (i) administering to the subject a photosensitizer drug; (ii) inserting a balloon catheter through a body orifice, the balloon catheter having (a) a proximal end that is fluidically couplable to a source of pressurized liquid, (b) an inflatable balloon section at its distal end portion, and having (c) a working channel; (iii) axially advancing and guiding the catheter until the inflatable balloon section is within proximity of said target site; (iv) inserting an optical probe, in a leakage-proof manner, into said working channel, the optical probe being optically couplable at its proximal end to a light source and having a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from said light diffuser in a non-axial direction; (v) axially advancing the optical probe through said working channel to position the light-diffusing section within said inflatable balloon section; (vi) forcing liquid to pass through the working channel to thereby inflate the inflatable balloon section until the balloon occupies a large portion of the volume of the endoluminal cavity while fixing the optical fiber in position with respect to the balloon catheter; and (vii) irradiating light through said optical probe at a wavelength and intensity suitable for activating the photosensitizer drug. In some embodiments, the method comprises imaging the target site, and in an imaging guided manner positioning said light-diffusing section within said inflatable balloon section. In some embodiments of the method, the inflatable balloon section comprises one or more balloon-associated imaging markers, and the light-diffusing section comprises one or more probe-associated imaging markers.

In some embodiments of the method, the positioning is through alignment of the one or more probe-associated imaging markers and the one or more balloon-associated imaging markers. In some embodiments of the method, the photosensitizer drug is a bacteriochlorophyll derivative having a major light absorption at about 750-756 nm, e.g., about 753 nm, and capable of generating oxygen radicals upon illumination. The photosensitizer drug may be administered to the subject for a time period before or concurrently with the inflation of the inflatable balloon section and the initiation of light irradiation. In some embodiments of the method, the light source may be a laser emitting light at a wavelength of about 750-756, e.g., 753 nm, with a power of at least about 0.5, 1, 2, 5, 7, 10, 20, 30, 40 or up to about 50 Watts, delivered to the optical probe. In some embodiments of the method, the photosensitizer drug is administered to the subject intravenously. The photosensitizer drug may be Padeliporfin (WST11). Moreover, in some embodiments of the method, the photosensitizer drug is administered between about 5 to about 15 min., typically about 10 min., before light irradiation is initiated. In some embodiments of the method, the PDT is vascular targeted phototherapy (VTP). In some embodiments of the method, the endoluminal cavity is the bladder or a portion of the gastrointestinal tract, e.g., colon, esophagus, biliary duct, gall bladder, and the target site is a tumor. In some embodiments of the method, the endoluminal cavity may be the bladder and the tumor is non-muscle-invasive bladder cancer (NMIBC). Where the target organ is the bladder, the balloon catheter system may be inserted through a ureteroscope, know per se. In some embodiments of the method, the inflatable balloon section is inflated to maintain a minimum distance between the light-diffusing section and the bladder wall, permitting illumination of substantially the entire lining of the bladder. The minimum distance may be at least 1, 2 or at least 3 cm. In some embodiments of the method, the photosensitizer drug is administered locally into an artery feeding blood to said target site, for example, be the method of the delivery aspect described below. In some embodiments, the method makes use of the system provided in this disclosure.

The method of some embodiments of this disclosure, a VTP of a target site in an endoluminal cavity of a subject comprises administering to the feeder arteries of the target tissue a VTP-effective drug at an amount required for vascular targeted phototherapy. Such a delivery is the subject of the feeding aspect described below. The method of some embodiments, further comprises (i) inserting elements of a system as described herein, e.g. through a body orifice or an incision, and axially advancing and guiding it until the inflatable balloon section is in the vicinity of the target site; (ii) axially displacing the optical fiber to position the light-diffusing section within said inflatable balloon section; and (iii) inducing a treatment stage. The treatment stage comprises (a) inflating the inflatable balloon with liquid to cause the balloon to occupy substantial portion of the endoluminal cavity and fix the optical fiber in position with respect to the balloon catheter, and (b) irradiating light through the optical fiber at a wavelength and intensity suitable for activating the photosensitizer drug. Feeding Aspect Provide by the feeding aspect is a system for use in a vascular-targeted photodynamic therapy (VTP) that comprises a catheter injection system having a distal portion that is configured for insertion into a feeder artery of a target tissue for the VTP treatment. It comprises a VTP injection device coupled to a proximal end of the delivery catheter and for forcing VTP-type drug into the catheter, the VTP being fed into said feeding artery resulting in blood concentrations suitable for VTP procedures in the target tissue. The method by an embodiment of this aspect comprises introducing a VTP-effective drug in arteries of the subject and irradiating a target organ or tissue with a VTP-effective light. The introducing comprises inserting a distal end portion of a delivery catheter into an artery that feeds blood into the target tissue or organ and propelling the VTP-effective drug through delivery artery and irradiating the VTP-effective drug onto the target tissue or organ. The irradiation can be performed at the time of said introducing or initiated shortly before or shortly after the drug introduction is initiated. By one embodiment, the light irradiation of the target organ or tissue is performed through a diffuser section of a light probe inserted into blood vessel other than said feeder artery.

By one embodiment, the target organ is an endoluminal cavity such as the bladder or the gastrointestinal tract. The irradiation may comprise inserting a balloon catheter through a body orifice or incision, the balloon catheter having (i) a proximal end that is fluidically couplable to a source of pressurized liquid, (ii) an inflatable balloon section at its distal end portion, and having (iii) a working channel; axially advancing and guiding the catheter until the inflatable balloon section is within proximity of said target site; inserting an optical probe, in a leakage-proof manner, into said working channel, the optical probe being optically couplable at its proximal end to a light source and having a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from said light diffuser in a non-axial direction; axially advancing the optical probe through said working channel to position the light-diffusing section within said inflatable balloon section; forcing liquid to pass through the working channel to thereby inflate the inflatable balloon section until the balloon occupies a large portion of the volume of the endoluminal cavity while fixing the optical fiber in position with respect to the balloon catheter; inserting a distal end portion of a delivery catheter into an artery that feeds blood into the target tissue or organ and propelling the VTP-effective drug through delivery artery; and irradiating light through said optical probe at a wavelength and intensity suitable for activating the VTP-effective drug. By another embodiment the target site is imaged and then in an imaging guided manner said light-diffusing section is positioned within said inflatable balloon section. The inflatable balloon section may comprise one or more balloon-associated imaging markers, and the light-diffusing section comprises one or more probe-associated imaging markers; and said positioning may then be through alignment of the one or more probe-associated imaging markers and the one or more balloon-associated imaging markers. The VTP-effective drug may be a bacteriochlorophyll derivative having a major light absorption of about 753 nm, and capable of generating oxygen radicals upon illumination. By one embodiment said VTP-effective drug is administered to the subject for a time period before or concurrently (time for the blood to pass through the entire treated area) with the inflation of the inflatable balloon section and the initiation of light irradiation. For example, in the case that the target organ is the bladder and the VTP drug is fed directly into the internal iliac artery or the superior vesical arteries that feed drug into the bladder, the VTP-effective drug may be infused into the artery 1 minute before or less; or initiate the drug infusion and the light irradiation at about the same time. Generally, this disclosure is not limited by the relationship between the onset of the drug infusion and the light irradiation and in some procedures it may be desired to begin to light irradiate the target tissue or organ before the drug is introduced into the feeder artery. A typical, albeit non-exclusive, option for the VTP-effective drug is Padeliporfin (WST11). Provided is also a system for vascular targeted photodynamic therapy (VTP), that comprises a catheter system having a proximal end that is configured for coupling with a source of VTP-effective drug and a distal end configured for insertion into an artery and navigating to an artery that feeds blood to an organ or tissue that is a target of said therapy. This system may be used, for example in any of the methods (of both the cavity treatment aspect and the feeding aspect) described herein.

EMBODIMENTS In the following sections embodiments will be listed in numbered passages intended to add onto the above description and not limit it in any way. The embodiments include such drafted in an independent format and other that dependent from such independent embodiments and may add additional elements to or modify embodiments from which they depend. Embodiments that are depended on one or more embodiments may also constitute elements that add to or modify other embodiments from which they do not depend. 1. A catheter system, comprising an optical probe and a balloon catheter, each of which axially extends between respective proximal and distal ends: the optical probe being optically couplable at its proximal end to a light source, having a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from said light diffuser in a non-axial direction, and having one or more probe-associated imaging markers at said distal end portion; and the balloon catheter having a proximal end being fluidically couplable to a source of pressurized liquid, an inflatable balloon section at its distal end portion capable of inflation to occupy a substantial portion of an body cavity, e.g. an endoluminal cavity, a working channel capable of accommodating the optical probe introduced through the proximal end in a leakage proof manner, the working channel being configured for fixing the optical probe in position with respect to said inflatable balloon while in an inflated state, and having one or more balloon-associated imaging markers associated with the inflatable balloon section. 2. The system of embodiment 1, comprising at least two probe-associated imaging markers flanking the light-diffusing section of said probe. 3. The system of embodiment 1 or 2, comprising two balloon-associated imaging markers associated with said inflatable balloon section. 4. The system of any one of embodiments 1-3, wherein the balloon-associated and the probe-associated imaging markers are X-ray markers. 5. The system of embodiment 4, wherein the balloon-associated and the probe-associated imaging markers are annular metallic elements. 6. The system of any one of embodiments 1 to 5, wherein the optical probe is axially displaceable within the catheter working channel until the light diffusion section is within the inflatable balloon section. 7. The system of any one of embodiments 1 to 6, wherein said inflatable balloon is configured for a high inflation to deflation ratio. 8. The system of embodiment 7, wherein the ratio between the diameter of the inflatable balloon in the inflated state to the diameter in a deflated state is at least 5:1. 9. The system of any one of embodiments 1 to 8, wherein the pressurized liquid is free of light-scattering elements. 10. The system of any one of embodiments 1 to 9, wherein said liquid is water or saline. 11. The system of embodiment 10, wherein said liquid is saline comprising between about 1% and about 2%, 3%, 4%, 5%, 10%, 15% or about 20% (v/v) X-ray contrast material. 12. The system of any one of embodiments 1 to 11, for use in photodynamic therapy (PDT). 13. The system of embodiment 12, wherein said PDT is vascular targeted phototherapy (VTP). 14. The system of any one of embodiments 1 to 13, wherein the balloon catheter is configured for insertion through a body orifice leading to a body cavity, e.g. an endoluminal cavity, and wherein the inflatable balloon section is configured, when in said deflated state, to occupy substantially a large portion of the volume of said cavity. 15. The system of embodiment 14, wherein the body cavity is the bladder or a portion of the gastrointestinal tract. 16. The system of any one of embodiments 1 to 15, wherein an inner face at a distal end portion of the working channel has a surface structure that is configured for fixing said optical probe in position with respect to the balloon catheter in said inflatable state. 17. The system of embodiment 16, wherein said inner face is serrated, porous, or rough. 17A. The system of embodiment 16, wherein said inner face is smooth. 18. The system of any one of embodiments 1 to 17, wherein said working channel is configured to permit convection cooling of the diffuser by permitting exchange of fluid that surround the diffuser with the fluid within the balloon. 18A. The system of embodiment 18, wherein the working channel has a terminal section that is detached from proximal sections of the channel. 18B. The system of embodiment 18, wherein the working channel has openings in its wall in sections the encompass the light diffuser during light irradiation. 19. The system of any one of embodiments 1 to 18B, comprising a source of light emitting light at a wavelength in the range of 750-756 nm and couplable to the proximal end of said light probe. 20. The system of embodiment 19, having an output power of above about 0.5, 1, 2, 5, 7, 10, 20, 30, 40 or up to 50 Watts. 21. The system of any one of embodiments 1-20, for use in a vascular-targeted photodynamic therapy (VTP) comprising: an arterial catheter injection system configured for insertion into a feeder artery of the target tissue. 22. A method for photodynamic therapy (PDT) of a target site in an endoluminal cavity of a subject, comprising in the indicated order or any other suitable order to achieve the purpose: administering to the subject a photosensitizer drug; inserting a balloon catheter through a body orifice or incision, the balloon catheter having (i) a proximal end that is fluidically couplable to a source of pressurized liquid, (ii) an inflatable balloon section at its distal end portion, and having (iii) a working channel; axially advancing and guiding the catheter until the inflatable balloon section is within proximity of said target site; inserting an optical probe, in a leakage-proof manner, into said working channel, the optical probe being optically couplable at its proximal end to a light source and having a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from said light diffuser in a non-axial direction; axially advancing the optical probe through said working channel to position the light-diffusing section within said inflatable balloon section (may be before and at, in some cases, also after inflating the balloon); forcing liquid to pass through the working channel to thereby inflate the inflatable balloon section until the balloon occupies a large portion of the volume of the endoluminal cavity while fixing the optical fiber in position with respect to the balloon catheter; and irradiating light through said optical probe at a wavelength and intensity suitable for activating the photosensitizer drug. 23. The method of embodiment 22, comprising: imaging the target site, and in an imaging guided manner positioning said light-diffusing section within said inflatable balloon section. 24. The method of embodiment 23, wherein said inflatable balloon section comprises one or more balloon-associated imaging markers, and said light-diffusing section comprises one or more probe-associated imaging markers; and wherein said positioning is through alignment of the one or more probe-associated imaging markers and the one or more balloon-associated imaging markers. 25. The method of any one of embodiments 22-24, wherein the photosensitizer drug is a bacteriochlorophyll derivative having a major light absorption around 753 nm, and capable of generating oxygen radicals upon illumination. 26. The method of embodiment 25, wherein said photosensitizer drug is administered to the subject for a time period before or concurrently with the inflation of the inflatable balloon section and the initiation of light irradiation, and wherein the light source is a laser emitting light at a wavelength of about 750-756, e.g., 753 nm, with a power of at least about 0.5, 2, 5, 7, 10, 20, 30, 40 or up to about Watts, delivered to the optical probe. 27. The method of embodiment any one of embodiments 22 to 26, wherein said photosensitizer drug is administered to the subject intravenously. 28. The method of any one of embodiments 22 to 27, wherein said photosensitizer drug is Padeliporfin (WST11). 29. The method of any one of embodiments 22 to 28, wherein the photosensitizer drug is administered between about 5 to about 15 min. before light irradiation is initiated. 30. The method of any one of embodiments 22 to 29 wherein said PDT is vascular targeted phototherapy (VTP). 31. The method of any one of embodiments 22 to 30, wherein the body cavity is the bladder or a portion of the gastrointestinal tract, and wherein the target site is a tumor. 32. The method of embodiment 31, wherein the cavity is the bladder and the tumor is non–muscle-invasive bladder cancer (NMIBC). 33. The method of embodiment 31 or 32, wherein the inflatable balloon section is inflated to maintain a minimum distance between the light-diffusing section and the bladder wall, permitting illumination of substantially the entire lining of the bladder. 34. The method of embodiment 33, wherein said minimum distance is at least 1, 2 or at least 3 cm. 35. The method of any one of embodiments 22 to 34, wherein the photosensitizer drug is administered locally into an artery feeding blood to said target site; for example by the method of any one of embodiments 37 to 50 or by the use of the system of embodiment 51. 36. The method of any one of embodiments 22 to 35, comprising use of the system of any one of embodiments 1 to 21. 37. A method for vascular targeted phototherapy (VTP) of a target site in a subject, comprising: administering a VTP-effective drug to the feeder arteries of the target site at an amount sufficient for vascular targeted phototherapy. 38. A method of embodiment 37 comprising: inserting a system of any one of embodiments 1 to 21 through a body orifice or incision and axially advancing and guiding it until the inflatable balloon section is in the vicinity of the target site; axially displacing the optical fiber to position the light-diffusing section within said inflatable balloon section; and inducing a treatment stage comprising inflating the inflatable balloon with liquid to cause the balloon to occupy substantial portion of the endoluminal cavity and fix the optical fiber in position with respect to the balloon catheter, and irradiating light through the optical fiber at a wavelength and intensity suitable for activating the photosensitizer drug. 39. A method for vascular targeted photodynamic therapy (VTP) of a subject, comprising: introducing a VTP-effective drug in arteries of the subject and irradiating a target organ or tissue with a VTP-effective light; wherein said introducing comprises inserting a distal end portion of a delivery catheter into a feeder artery, being an artery that feeds blood into the target tissue or organ and propelling the VTP-effective drug through delivery artery, and irradiating the VTP-effective drug onto the target tissue or organ. 40. The method of embodiment 39, comprising in the given order or any other suitable order: inserting a balloon catheter through a body orifice or incision, the balloon catheter having (i) a proximal end that is fluidically couplable to a source of pressurized liquid, (ii) an inflatable balloon section at its distal end portion, and having (iii) a working channel; axially advancing and guiding the catheter until the inflatable balloon section is within proximity of said target site; inserting an optical probe, in a leakage-proof manner, into said working channel, the optical probe being optically couplable at its proximal end to a light source and having a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from said light diffuser in a non-axial direction; axially advancing the optical probe through said working channel to position the light-diffusing section within said inflatable balloon section; forcing liquid to pass through the working channel to thereby inflate the inflatable balloon section until the balloon occupies a large portion of the volume of the endoluminal cavity while fixing the optical fiber in position with respect to the balloon catheter; inserting a distal end portion of a delivery catheter into an artery that feeds blood into the target tissue or organ and propelling the VTP-effective drug through delivery artery; and irradiating light through said optical probe at a wavelength and intensity suitable for activating the VTP-effective drug. 41. The method of embodiment 40, comprising: imaging the target site, and in an imaging guided manner positioning said light-diffusing section within said inflatable balloon section. 42. The method of embodiment 41, wherein said inflatable balloon section comprises one or more balloon-associated imaging markers, and said light-diffusing section comprises one or more probe-associated imaging markers; and wherein said positioning is through alignment of the one or more probe-associated imaging markers and the one or more balloon-associated imaging markers. 43. The method of any one of embodiments 39-42, wherein the VTP-effective drug is a bacteriochlorophyll derivative having a major light absorption around 753 nm, and capable of generating oxygen radicals upon illumination. 44. The method of embodiment 43, wherein said VTP-effective drug is administered to the subject for a time period before or concurrently with the inflation of the inflatable balloon section and the initiation of light irradiation, and wherein the light source is a laser emitting light at a wavelength of about 750-756, e.g., 753 nm, with a power of at least about 0.5, 1, 2, 5, 7, 10, 20, 30, 40 or up to about Watts, delivered to the optical probe. 45. The method of any one of embodiments 39 to 44, wherein said VTP-effective drug is Padeliporfin (WST11). 46. The method of any one of embodiments 39 to 45, wherein the endoluminal cavity is the bladder or a portion of the gastrointestinal tract, and wherein the target site is a tumor. 47. The method of embodiment 46, wherein the endoluminal cavity is the bladder and the tumor is non– muscle-invasive bladder cancer (NMIBC). 48. The method of embodiment 46 or 47, wherein the inflatable balloon section is inflated to maintain a minimum distance between the light-diffusing section and the bladder wall, permitting illumination of substantially the entire lining of the bladder. 49. The method of embodiment 48, wherein said minimum distance is at least 1, 2 or at least 3 cm. 50. The method of embodiment 39, wherein the light irradiation of the target organ or tissue is performed through a diffuser section of a light probe inserted into blood vessel other than said feeder artery. 51. A system for vascular targeted photodynamic therapy (VTP), comprising: a catheter system having a proximal end that is configured for coupling with a source of VTP-effective drug and a distal end configured for insertion into an artery and navigating to an artery that feeds blood to an organ or tissue that is a target of said therapy. 52. The system for treating a target organ or tissue by VTP, comprising: a source of VTP-effective drug; a catheter system couplable at its proximal end to the source of VTP-effective drug, having a distal end configured for insertion into an artery, and having an associated manipulation arrangement for navigating its proximal end to a feeder artery that feeds blood to the target organ or tissue. 53. The system of embodiment 51 or 52, wherein the source of VTP-effective drug is configured for delivering an amount of drug to yield a drug level in said organ or tissue that is effective for the VTP-based therapy. 54. The system of any one of embodiments 51 to 53, wherein the target organ is the bladder. 55. The system of embodiment 54, for treating a balder tumor, for example non– muscle-invasive bladder cancer (NMIBC). 56. The system of any one of embodiments 51 to 55, wherein said VTP-effective drug is Padeliporfin (WST11). 57. The system of any one of embodiments 51 to 56, for use in the method of any one of embodiments 39-51. 58. The system of any one of embodiments 51 to 56, for use in the method of any one of embodiments 22 to 38.

BRIEF DESCRIPTION OF THE FIGURES In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: Fig. 1 is a schematic representation of an exemplary embodiment of a system of the cavity treatment aspect of this disclosure, for treating the bladder, with its distal end positioned within the bladder, and with the inflated balloon section being inflated. Fig. 2 is a schematic representation of the distal portion of the system of Fig. 1 in isolation, illustrating various of its elements.

Fig. 3 is a schematic representation of the distal portion of the system of Fig. illustrating an optional working channel bridge. Fig. 4 is a schematic representation of the distal portion of a system of another embodiment of the cavity treatment aspect of this disclosure including an optional auxiliary balloon. Fig. 5 is a flow diagram of a non-limiting example of the method according to the cavity treatment aspect of the present disclosure. Fig. 6 is a flow diagram of a non-limiting example of the method according to the feeding aspect of the present disclosure. Fig. 7 is a schematic representation of direct feeding of a VTP-effective drug into a feeder artery of the bladder within the framework of treatment of the DETAILED DESCRIPTION OF SOME EMBODIMENTS The following description concerns some exemplary embodiments, described in references to the annexed figures. As can be appreciated, this disclosure is not limited to these exemplary embodiments that encompasses to the full scope disclosed above and claimed below. Figs. 1-3 depict schematic representations of an exemplary embodiment of a system according to the cavity treatment aspect of this disclosure, for treating a bladder cancer. The catheter system 100 comprising an optical probe 102 , a balloon catheter 104 and guiding urethral catheter 106 , which may be a ureteroscope or cystoscope, all of which axially extend between respective proximal and distal ends 108 , 110 . The system 100 is usable in photodynamic therapy (PDT), wherein the PDT may be vascular targeted phototherapy (VTP). The optical probe 102 is optically coupled at its proximal end to a light source 112 , typically a laser source, which may emit light at wavelength suitable for activating the PDT drug, which in the case of Padeliporfin is, typically, about 753 nm, and having an output power of above about 0.5, 2, 5, 7, 10, 20, 30, 40 or 50 Watt. The optical probe 102 comprises an optical fiber 113and has a light-diffusing section 114 at a distal end portion 116 configured for scattering light transmitted through the probe 102 , such that at least portion thereof is transmitted from the light-diffusing section 114 in a non-axial direction, e.g., substantial portion in the radial direction, as schematically represented by dotted arrows 115 . The optical probe 102 has a pair of probe-associated imaging markers 118 , flanking the light-diffusing section. In other embodiments, rather than a pair of such markers, there may be 1, 3 or more such markers. The balloon catheter 104 is fluidically coupled to arm 119of Y-connector 120which is in turn coupled via its arm 121 to a source of pressurized liquid, such as pump 122through an adapter or valve 124 . The pressurized liquid is typically water or saline, optionally comprising a 10% v/v X-ray contrast agent. The optical fiber 113 is accommodated within working channel 126 of the balloon catheter 104and is introduced through arm 128of Y-connector 120 in leakage proof manner to thereby prevent back-flow. The Y-connector 120 may, for example, may have an integral seal in arm 128, e.g. Merit Medical MRTMAP150. The balloon catheter 104 also has an inflatable balloon section 130 at its distal end portion 116 , that can be inflated to occupy a substantial portion of an endoluminal cavity 132 , in this example bladder cavity within bladder 134 . Associated with the balloon catheter 104are a pair of balloon-associated imaging markers 136 within the inflatable balloon section 130 that together with the diffuser-associated markers (see below) serve for proper location the diffuser. (In other embodiments, rather than a pair of such markers, there may be 1, 3 or more such markers.) The balloon-associated imaging markers 136and the probe-associated imaging markers 118 may be X-ray markers, e.g. in the form of an annular element made of a metal such as gold, a metal alloy, or a radiopaque plastic. The optical probe 102 is axially displaced within the catheter working channel 126 until the light diffusion section 114 is within the inflated balloon section 130 . Such positioning of the light diffusion section 114within the inflated balloon section 130 is typically performed under imaging guidance by observing that the pair of imaging markers 118 are within the confines of imaging markers 136 , achieving the alignment schematically represented in Figs. 2 and 3. An inner face 127at a distal end portion of the working channel 126 may have a surface structure, e.g. being smooth, serrated, porous or rough that serves, during inflation of the balloon and through the hydrostatic pressure within the balloon that also acts on the walls of the working channel, to hold the optical fiber 113 . In the specific embodiment of Fig. 2., the terminal section 145 of the working channel is detached from the main part of the working channel, with the diffuser being consequently exposed to the liquid with the inflated balloon allowing liquid circulation around the diffuser. Such circulation allows for cooling of the diffuser. In the specific embodiment of Fig. 3, the distal section 140 of the balloon working channel is linked to the remainder of the catheter by means of a bridge 142thereby keeping alignment between the proximal and distal sides of the working channel within the inflatable balloon section. In other embodiments not shown, the working channel may extend through the entire inflatable balloon section but may have openings, holes, slits, etc. to allow the circulation of fluid between the balloon cavity and the fiber diffuser section 114 . The inflation is performed by pumping in saline using balloon pump 122 , and the saline 131 filling the balloon’s interior is, typically, without particular matter so as to provide optimal optical properties for light transmission therethrough. The saline may comprise a contrasting agent as noted above. The inflatable balloon section 130 may be configured for a high inflation to deflation ratio, such that the ratio between the diameter of the balloon between its inflated state to its diameter in a deflated state is at least 5:1, optionally 7:1, 10:1 or even higher. Guiding urethral catheter, ureteroscope, or cystoscope 106 is configured for insertion through the urethra and provides a channel for axially displacing the balloon catheter 104 therethrough. While the specifically described embodiment concerns the bladder, the disclosure herein is not limited to this clinical use and applies to the full scope described above, including, among others, the gastrointestinal tract (such as colon, esophagus, biliary duct, gall bladder, stomach, etc.), with the system being inserted, as the case may be, from the annus or from the mouth and parts of the respiratory system. Fig. 4 shows a schematic representation of the distal portion of a system of another embodiment of the cavity treatment aspect, including an optional auxiliary balloon 244 . In Fig. 4, like elements to those of the exemplary embodiment of Figs. 1-3 have been given like reference numerals shifted by 100. For example, optical fiber 213 in Fig. 4 is like optical fiber 113of Figs. 1-3. The reader is referred to the above description for explanation of their nature and function. The optional auxiliary balloon 244 serves to hold the balloon in place during the procedure. The optional auxiliary balloon 244may be inflated jointly with the main balloon 230 or separately, being supplied with inflating fluid through a separate channel. Additionally, the balloon catheter may include its own dedicated channel for inflating the balloon as is commonly used in angioplasty catheters. In this case, the balloon pump connects directly to the balloon inflation port. The y-connector is replaced by a Touhy Borst adapter on the balloon working channel. Fig. 5 is a flow diagram of an exemplary method for photodynamic therapy (PDT), according to the cavity treatment aspect of this disclosure, which may be a vascular targeted phototherapy (VTP), of a target site in an endoluminal cavity of a subject according to this disclosure. The order of steps may be that described or another suitable order according to other embodiments of this disclosure. The endoluminal cavity may be the bladder or a portion of the gastrointestinal tract (e.g., colon, esophagus, biliary duct, gall bladder), and the target site may be a tumor. Moreover, the tumor may be a non-muscle invasive bladder cancer (NMIBC). The method comprises administering to the subject a photosensitizer drug 350 . The photosensitizer drug may be a bacteriochlorophyll derivative having a major light absorption at about 750-756 nm, e.g., about 753nm, and capable of generating oxygen radicals upon illumination. Moreover, the photosensitizer drug may be Padeliporfin (WST11). The administration of the photosensitizer drug 350 may intravenous or may be done locally into an artery feeding blood to the target site. While step 350 is represented as the first step in this process, as can be appreciated, the photosensitizer drug may be administered in other steps of the process, such as, for example, after step 364 of inflating the inflatable balloon section. If the drug is administered by the use of an arterial catheter injection system, which may be configured for administration of a VTP-effective drug into the feeder artery of the target tissue. The amount of injected drug is such so as to result in a blood consecration suitable for the intended PDT procedure. In the performance of the method a system of this disclosure is inserted through a body orifice 352 which may be the urethra in the case of the bladder. The balloon catheter has (1) a proximal end that is fluidically couplable to a source of pressurized liquid, (2) an inflatable balloon section at its distal end portion, and (3) a working channel. The method further comprises axially advancing and guiding the balloon catheter 354 until the inflatable balloon section is within proximity of the target site. Then the optical probe is inserted 356 , in a leakage-proof manner, into the working channel. The optical probe being optically coupled at its proximal end to a light source and having a light-diffusing section at a distal end portion configured for scattering light transmitted through the probe, such that at least a portion thereof is transmitted from the light diffuser in a non- axial direction, and then axially advancing the optical probe 358 through the working channel to position to the light-diffusing section within the inflatable balloon section. The target site may be imaged 360 , in an imaging-guided manner, the light-diffusing section may then be positioned 362within the inflatable balloon section. The inflatable balloon section and the light-diffusing section, each comprises one or more imaging markers. The positioning of the light-diffusing section 362 is being done though alignment of the imaging markers of the light-diffusing section and those of the inflatable balloon section. The inflatable balloon section is then inflated 364 by forcing pressurized liquid through the working channel to cause the balloon to occupy substantially a large portion of the volume of the endoluminal cavity. The inflated balloon section may be inflated to maintain a minimum distance of at least 1, 2 or 3 cm, between the light-diffusing section and the bladder wall, permitting illumination of substantially the entire lining of the bladder. Light is then irradiated 366 through the optical probe at a wavelength and intensity suitable for activating the photosensitizer drug. The administration of the photosensitizer drug to the subject 350 may occur prior to or concurrently with the inflation of the inflatable balloon section 364 and the subsequent irradiation 366 . The administration of the photosensitizer drug 350 may occur about 5 to about 15 minutes, typically about 10 minutes, before the light irradiation 366 is initiated. The light source may be a laser emitting light, e.g. wavelength of about 750-756nm, with power of at least about 0.5, 1, 2, 5, 7, 10, 20, 30, 40 or up to about 50 Watts, delivered to the optical probe. Fig. 6 is a flow diagram of an exemplary method for photodynamic therapy (PDT), according to the feeding aspect of this disclosure. The order of steps may be that described or another suitable order according to other embodiments of this disclosure. In this exemplary embodiment a delivery catheter is inserted 468into a major accessible artery, e.g., the femoral artery, and then the distal, delivery end of the catheter is navigated 470into a feeder artery, directly feeding blood to the target tissue or organ. The proximal end of the catheter is connected to a source of a VTP-type drug. A light diffuser is positioned in situ 472 , namely at the location which light irradiation through the diffuser will reach the target organ or tissue. The light diffuser is at a distal end of an optical probe which is coupled at its proximal end to a light source, e.g., laser source, that can transmit light which is effective in activating the VTP-type drug. The light diffuser is inserted through a body orifice or an incision, and then displaced until it reaches its intended site. The placement of the diffuser in situ may, for example, be in a manner described above or as described in WO 2023/131953; the feeder artery may differ depending on the type of target organ or tissue. The source of VTP-type drug is activated to propel 474 the drug through the delivery system to be ejected out of the distal end into the feeder artery and from there to the target organ or tissue. Irradiating VTP-effective light 476 , fed from the light source coupled to the probe’s proximal end, then activates the drug. The light irradiation may be initiated concurrently with propelling of the drug or may be initiated shortly thereafter; albeit it is possible also, for some applications, to initiate the light irradiation before initiation of the delivery of the VTP-typed drug. An example of the feeding aspect of this disclosure in the bladder is described below. Direct infusion of the feeder artery is intended to isolate the VTP affect to the target organ, which requires that concentration of the drug in the organ is much higher than in the surrounding non-target tissues. The average bladder receives 3.2ml/min of blood derived from an average bladder weight of 42gram (Housami et al., Indian J Urol. 25(1):105-109, 2009) and flow rate of 7.6ml/min in 100g of tissue (Kershen et. al, J. Urol. 168: 121-5, 2002). For this calculation, 5ml/min of blood flow through the bladder will be assumed along with a 10% blood mass ratio in tissue, implying that the bladder is 4.2g of blood or approximately 4.2ml of blood. The typical VTP illumination is 10 minutes. During such 10 minutes, 50ml of blood is transmitted through the bladder. The average human has approximately 5000ml of blood. Thus, if bladder specific WST11 infusion is used, then only 50ml/5000ml, namely 1% of a typical WST11 dose is required over the illumination. Assuming that 1 minute of WST11 infusion in the bladder is required before illumination to infuse the entire organ, then 1% of the WST11 is used for infusing the bladder feeder artery versus the standard intravenous dose having the obvious benefit of isolating the VTP effect to the bladder. Isolation occurs in three ways: 1) direct infusion into the bladder feeder artery, 2) low concentration outside of the target tissue, and 3) illumination around the time of infusion which does not allow for the drug to uniformly spread through the body. Fig. 7 is a general schematic representation of the feeding aspect to target the bladder. A catheter infusion system 500 , coupled at its proximal end 502to a source of a VTP-effective drug, in this example a pump 504for the administration of Padeliporfin (WST11), is inserted through an artery and its distal portion 506 is navigated via the common iliac artery into the internal iliac artery, that is the feeder artery to the bladder through the superior vesical arteries that branch therefrom. A similar method was used for directly targeting the bladder for chemotherapy in rats: drug infusion was directly into the internal iliac artery to get higher drug concentration in the bladder (Houshi et al., Int J Urol. 4(5):493-499, 19997). The infusion pump 504(For example, B. Braun Perfusor Space) provides WST11 at the flow rate (that may be measured by an internal flow meter) required to obtain about 40mg/kg in blood corresponding to the 4mg/kg in per total body mass typically attained in PDT methods. Infusion may begin slightly before or at the start of illumination to obtain the required WST11 concentration during the illumination. An exemplary calculation of the flow rate is shown in the table below (as the pharmacokinetics numbers should be taken as general guidelines and not precise values to be obtained). Using a WST11 concentration of 1mg/ml in solution, give rise to a flow rate of about 0.2ml/min of WST11 solution pumped directly into the feeder artery to result in approximately 4mg/kg WST11 concentration required for achieving the VTP effect. parameter unit value notesbladder blood flow rate ml/min 5 literature estimate target WST11 concentration mg/kg 4 no Cmax correction, may be less blood percent in body 0.1 typical target WST11 concentration in blood mg/kg 40 blood density kg/L 0.994 WST11 concentration in blood mg/ml 0.03976 WST11 flow rate in bladder mg/min 0.1988 WST11 solution concentration mg/ml 1 standard vial is total WST11 for 10 minutes mg 1.988 WST11 solution flow rate ml/min 0.1988 20

Claims (16)

- 28 - CLAIMS:

1. A method for vascular targeted phototherapy (VTP) of a target site in a subject, comprising: administering a VTP-effective drug to a feeder artery of the target site at an amount sufficient for vascular targeted phototherapy.

2. A method for vascular targeted photodynamic therapy (VTP) of a subject, comprising: introducing a VTP-effective drug in arteries of the subject and irradiating a target organ or tissue with a VTP-effective light; wherein said introducing comprises inserting a distal end portion of a delivery catheter into a feeder artery, being an artery that feeds blood into the target tissue or organ and propelling the VTP-effective drug through delivery artery, and irradiating the VTP-effective drug onto the target tissue or organ.

3. The method of claim 1 or 2, wherein the VTP-effective drug is a bacteriochlorophyll derivative having a major light absorption around 753 nm, and capable of generating oxygen radicals upon illumination.

4. The method of claim 3, wherein said VTP-effective drug is administered to the subject for a time period before or concurrently with the inflation of the inflatable balloon section and the initiation of light irradiation, and wherein the light source is a laser emitting light at a wavelength of about 750-756, e.g., 753 nm, with a power of at least about 0.5 Watts, delivered to the optical probe.

5. The method of any one of claims 1 to 4, wherein said VTP-effective drug is Padeliporfin (WST11).

6. The method of any one of claims 2-5, wherein the target organ or tissue border a body cavity and the VTP-effective light is irradiated from within the cavity.

7. The method of claim 6, wherein the cavity is an endoluminal cavity.

8. The method of claim 6, wherein the endoluminal cavity is the bladder or a portion of the gastrointestinal tract, and wherein the target site is a tumor.

9. The method of claim 8, wherein - 29 - the endoluminal cavity is the bladder and the tumor is non-muscle-invasive bladder cancer (NMIBC).

10. The method of any one of claims 2-5, wherein the light irradiation of the target organ or tissue is performed through a diffuser section of a light probe inserted into blood vessel other than said feeder artery.

11. A system for vascular targeted photodynamic therapy (VTP), comprising: a catheter system having a proximal end that is configured for coupling with a source of VTP-effective drug and a distal end configured for insertion into an artery and navigating to an artery that feeds blood to an organ or tissue that is a target of said therapy.

12. The system for treating a target organ or tissue by VTP, comprising: a source of VTP-effective drug; a catheter system couplable at its proximal end to the source of VTP-effective drug, having a distal end configured for insertion into an artery, and having an associated manipulation arrangement for navigating its proximal end to a feeder artery that feeds blood to the target organ or tissue.

13. The system of claims 11 or 12, wherein the source of VTP-effective drug is configured for delivering an amount of drug to yield a drug level in said organ or tissue that is effective for the VTP-based therapy.

14. The system of any one of claims 11 to 13, wherein the target organ is the bladder.

15. The system of claim 14, for treating a balder tumor, for example non¬– muscle-invasive bladder cancer (NMIBC).

16. The system of any one of claims 11 to 15, wherein said VTP-effective drug is Padeliporfin (WST11). 25