MXPA01007487A - Method for improved radiation therapy - Google Patents

Abstract

A method is disclosed for treating a selected volume of tissue which method includes distributing a radiosensitizer and a plurality of ionizing radiation sources substantially within the volume of tissue to produce treatment zones that are generally uniformly distributed throughout the volume of tissue. An agent is also disclosed for treating such tissue, wherein the agent includes a radiosensitizer and an ionizing radiation source used in conjunction to define an injectable treatment agent.

Description

METHOD FOR IMPROVED RADIATION THERAPY BACKGROUND OF THE INVENTION The present invention relates to methods and compositions for radiation treatment of a select volume of tissue, such as the treatment of abnormal cell proliferation or malignant tissue. More specifically, the present invention relates to a novel method that involves distributing a radio sensitizer and a plurality of sources of ionizing radiation substantially within the volume of tissue to produce treatment zones that are generally evenly distributed throughout the tissue volume.

The present invention also relates particularly to a novel agent for treating this tissue where the agent includes a radio sensitizer and a source of ionizing radiation as a whole, to define an injectable treatment agent. It is well known that the abnormal cell proliferation that occurs in cancer, for example, is often treated using ionizing radiation in a process known as radiation therapy. In radiation therapy (which typically but not necessarily uses electromagnetic radiation with energies of 1 keV or higher), radiation can be applied from an external source or through the introduction of a radioactive source into the tissue to be treated. One of the well-known disadvantages of radiation therapy is the collateral damage to healthy tissue that surrounds the primary treatment site. Accordingly, a primary or fundamental challenge in radiation therapy is the selective delivery of a therapeutic dose of radiation to the desired tissue, such as in a cancerous tumor. One technique for locating the effect of radiation is to use dense radio or radio opaque radio sensitization agents in conjunction with the applied radiation. These agents improve the effect of radiation on the tissue treated with the sensitizer and in the past have produced dose improvements (DE = Dose Enhance ent) in tumors, when these agents are introduced into the tissue to be treated. The use of sensitizers, however, is only an advance, not the complete response in radiation therapy. There are a number of significant problems in the previous methods when this approach is used, especially in the uniform treatment of a desired treatment volume or tissue. For example, after administering radiopaque radio-sensitizing radioactive agent, uniform delivery of a therapeutic radiation dose to the entire treatment volume is often obstructed by portions of the treatment volume protected by the radio sensitizer. More specifically, when external radiation is used, where radiation is supplied from a source external to the body, the radio sensitizer in the treated tissue closest to the radiation source may tend to block or shield the tissue more distant from the radiation ionizing As a result, only part of the tissue to be treated receives an effective dose of radiation. Similarly, when a confined radiation source, such as a radioactive needle or tip of a wire or tape is introduced directly into or on the vicinity of the tissue to be treated (commonly referred to as brachytherapy), the sensing radio in proximity to the source of Radiation can act to shield the rest of the tissue from the desired dose. The result is less than the uniform treatment of tissue volume such as a tumor in question. Accordingly, a general objective of the present invention for improving the uniformity of radiation treatment for selected tissue volumes such as tumors and the like. Another object of the present invention is to provide methods and agents for treatment of tissue radiation that aid in providing a more uniform treatment to the desired tissue volume. SUMMARY OF THE INVENTION The present invention is directed to a method for treating a selected volume of tissue. The method comprises the steps of distributing a radio sensitizer within the volume of the tissue; and distributing a plurality of ionizing radiation sources within the tissue volume, with each radiation source producing a radiation treatment zone. The radiation sources are distributed within the tissue volume such that the treatment zones of the plurality of radiation sources are generally distributed through the volume of tissue and substantially all of the tissue in the select volume is within at least a treatment area. In a preferred embodiment of the present invention, the radio sensitizer and / or radiation sources are distributed substantially uniformly within the select volume to result in a more uniform treatment to the tissue within the select volume. According to another aspect of the present invention, each of the treatment zones may overlap at least one other treatment zone to better ensure effective treatment of the tissue in the selected volume. According to other aspects of the present invention, the distribution of a radio sensitizer and the distribution of ionizing radiation sources can be carried out sequentially or simultaneously by injecting them together, directly into or in proximity with the select volume of tissue or in another As an aspect of the present invention, the distribution of a radio sensitizer and the distribution of ionizing radiation sources can be carried out by sequential administration of the radio sensitizer and sources of ionizing radiation. To avoid undue effect on healthy tissue or other outside the select volume, according to another aspect of the present invention, the treatment zones of the radiation source preferably do not extend substantially beyond the selected volume of tissue. The present invention according to another aspect is also directed to a tissue treatment agent. Preferably, the agent comprises a radio sensitizing component and a source component of ionizing radiation, with the additive sensitizing component and the combined radiation source component to define an injectable treatment agent. The agent may be in any convenient way, but in preferred aspects of the present invention it is a liquid or gel. Also, the radio sensitizer and radio source can be conjugated to define an injectable agent. These are just a few of the aspects of the present invention set forth in the appended claims and described in the following detailed description of the invention. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates an example of shielding the inner and remote portions of a treatment region using prior treatment methods; Figure lb illustrates an example of shielding the distal portions of a treatment region using an internal source with prior treatment method; Figure 2a illustrates the effect of a single radioactive dispersible tumor material, in conjunction with a tumor-specific radio sensitizer in a desired treatment volume; Figure 2b illustrates a preferred embodiment of the present invention wherein multiple entities of radioactive dispersible tumor material are present in the treatment volume of Figure 2a; Figure 3a illustrates the binding of a radio sensitizing portion and a radioactive portion to produce a radio conjugate-sensitizer agent according to one embodiment of the present invention; Figure 3b illustrates a conjugated radio-sensitizing portion connected to a targeting portion for producing a sensitizing conjugate and a conjugated radio-active portion connected to a target portion to produce a radio conjugated agent, according to one embodiment of the present invention; and Figure 3c illustrates a radio sensitizing portion and a radioactive portion in a delivery vehicle, according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE CURRENTLY PREFERRED MODALITIES Figures la and lb illustrate blocking or radiation shielding problems in the prior art. In particular, the Figure shows an example of the shield 10 of the inner and remote portions of a treatment volume. In this example, a radiopaque sensitizer 16 has been distributed through the treatment volume 18, such as a malignant or cancerous tumor.

When the radiation 12 is applied using an external source 14, the closest sensitizer (20) to the external source 14 substantially absorbs a major portion of the radiation 12 before it can reach the distant localized sensitizer (22) to the external source. As a result, the inner and remote portions of the treatment volume 18 are protected from radiation 12 and the activation efficiency of the distant sensitizer 22, or located beyond a certain radiation penetration distance 24, is severely reduced. This self-shielding produces a non-uniform treatment, where most or all of the activation occurs in a sub-volume 26 which is confined primarily to that portion of the treatment volume 18 next to the source 14 (ie to a target separation). source within the radiation penetration distance 24). Even with multi-trajectory delivery, this shielding occurs in interior portions of the treatment volume, reducing the effectiveness of the total treatment regimen. Another example of the shield 30 is illustrated in Figure lb, where a contained internal source is employed, such as for example in brachytherapy. As illustrated in Figure lb, a radio opaque sensitizer 16 is distributed in a substantially uniform manner through the treatment volume 18. The shielding of distal portions of a treatment volume 18 occurs when the radiation 12 is applied using an internal source 32. The sensitizer present close to the internal source 34 substantially absorbs a major portion of the radiation 12 before it can reach the present sensitizer distant to the internal source 36, thereby shielding and reducing the activation efficiency of this distant sensitizer 36. located beyond a certain effective radiation penetration distance 24. This self-shielding produces a non-uniform treatment, where most or all of the activation occurs in a sub-volume 38 that is confined primarily to that portion of the treatment volume 18 next to the source 32 (ie to a source-target separation within the distance Effective penetration of radiation 24). In accordance with the present invention, and in contrast to the prior art, a method is provided for a more uniform radiation treatment of a selected volume of tissue such as a malignant mass or tumor. As illustrated in Figures 2a and 2b, the method of the present invention generally includes distributing a radio sensitizer 44 within the volume 46 of the tissue to be treated, and distributing a plurality of sources of ionizing radiation 42 within the volume. Each source of radiation 42 emits radiation in all directions that have an effective radius, but before being unduly shielded, blocked or attenuated by the sensitizer 44, tissue or other material in the tissue, to define a treatment zone 56 within the which radiation provides the desired dose enhancement effect that acts in conjunction with the radio sensitizer. The radiation sources are distributed through the volume of tissue, such that substantially all of the tissue in the treatment volume is within one or more treatment zones. Preferably, the radio sensitizer and radiation sources are distributed substantially uniformly through the selected volume of tissue to better provide a radioactive therapy generally uniform and effective to the select tissue volume. In a preferred embodiment of the present invention, multiple entities of a radioactive dispersible active material of tumor 42 in the form of radioactive multiple particles or nano-particles are located within the treatment volume as illustrated in Figure 2b. By increasing the concentration of these tumor dispersible radioactive material entities 42 in the treatment volume 46, such that the multiple localized treatment zones of the material 56 overlap, the treatment 64 performed within the desired total treatment volume 46. The material radioactive dispersible tumor serves, once distributed, preferably substantially uniformly throughout the tumor (wherein this distribution of one or more of the primary administrative sites occurs by natural dispersion, dilution or other physical passive distribution mechanisms substantially), as a uniformly dispersed source that produces substantially uniform radiation through the tumor volume. In addition, the use of these distribution mechanisms provides minimal effective radiation dose to healthy tissues outside the treatment zone. This uniform radiation results in a more uniform activation of the radio sensitizers through the tumor volume (due between the radiation source and target, i.e. the radioactive dispersible tumor material and radio sensitizer as discussed below), and from this way produces a simpler and more effective means to deliver a therapeutic dose of radiation therapy to the entire tumor. This mitigates the shielding effects of any given entity 42, greatly simplifying the calculation of dose and delivery. Since the tumor-specific sensitizing radio 44 is substantially present only within the desired treatment volume 46 as previously explained, the existence of a portion 66 of any radiation interaction volume 56 that extends beyond the desired treatment volume 46 , will not produce significant collateral damage in these adjacent irradiated volumes 68. It was also previously described, this provision of multiple entities of radioactive dispersible tumor material 46 can be easily effected through intratumoral injection of a solution of this material or other similar administrative techniques. such as nearby lymphatic or venous injection. The volume of treatment or select volume of tissue can be any particular tissue that is chosen for treatment. Typically, although not exclusively, the tissue to be treated will be a tissue in which there will be cell proliferation and which can be treated by ionizing radiation. Although this cell proliferation may be benign, it is anticipated that the present invention will find greater application in treatment of malignant tissue in the form of a tumor such as for example a cancerous tumor or other malignancy or a maseL of diseased tissue such as a cyst, polyp or abscess The present invention is not limited to the specific radio sensitizer employed. Specific examples of radio sensitizers that can be used including the various radio-dense halogenated xanthenes and their derivatives, such as Rose Bengal and its various derivatives. Folixin B and its various derivatives. Erythrosin B and its various derivatives. Eosin Y and its various derivatives, together with various other highly brominated or iodinated halogenated xanthenes and their various derivatives, such as 4.5, 6.7-Tetrabromoerythrosine; various X-ray contrast agents such as OmnipaqueHR (iohexol), OmniscanHR (gadodiamide), WIN 8883 (diatrizoic acid). and iodide and lipiodol, together with those agents that contain various dense radio elements or portions, such as iodine, bromine, chlorine, barium, bismuth, boron, gold, silver, platinum, iron, gadolinium, dysprosium and tantalum; iododeoxyuridine and bromodeoxyuridine and related agents; various halogenated nucleotides and DNA ligands and intercalators, including various agents based on imidazole and substituted acridine; various nitroimidazoles and other related bio-reducing agents; Misonidazole and related agents; etanidazole and related agents; pimondazole and related piperidine derivatives; aziridines and related agents; cyclophosphamide and related agents; nitrosoureas, and related agents; L-phenylalanine mustard and related agents; cis-platinum compounds and related agents; and doxorubicin and related agents. Preferably, the present invention utilizes a tumor-specific radio sensitizer such as halogenated xanthene. More preferably, the tumor-specific radio sensitizer is Rose Bengal. In general, these sensitizing radii can be introduced into the volume of treatment by systemic administration such as intravenous administration, direct injection, or similar conventional techniques. More preferably, this administration includes direct injection or other administrative techniques within or close to the desired volume of treatment. The use of these administrative techniques with various radio sensitizers, such as those described above, can lead to a localized retention and at a therapeutically useful level of these radio sensitizers within the desired treatment volume for a period of several hours to several weeks. As a result, the radio sensitizer becomes distributed substantially uniformly through the desired volume of treatment, through dispersion, dissolution or other passive equilibrium or concentration process, including preferential absorption. The method of the present invention further includes the step of distributing a plurality of sources of ionizing radiation. The present invention is not limited to the number of sources of ionizing radiation, but contemplates the use of more than one source of ionizing or other high-energy radiation. An example of this source, to be used in the present invention is a radioactive, tumor dispersible material as discussed previously. The present invention, however, is not limited to this radioactive material, as a radioactive, tumor dispersible material and the aforementioned radioactive portions, such as those discussed below, and other similar materials may also be used. Preferably, the one or more sources are located within the treatment volume. Furthermore, as explained below, it is preferred that a plurality of these radiation sources be distributed within the volume of the treatment. More specifically, Figure 2A illustrates the effect 40 of a single source of radiation, for example a tumor-dispersible radioactive material 42, located in a treatment volume wherein a quantity of tumor-specific radio-sensing 44, such as for example previously described, it is distributed in a substantially uniform form and contains within the treatment volume 46. "Tumor dispersible" means easily dispersible within a treatment volume, for example a tumor. Typically, a tumor-dispersible radioactive material may be a liquid, gel or other dispersible form or formulation of a radioactive material consisting of a color or fine particle suspension dissolved or otherwise solubilized or dispersible in the form of a radioactive material that is stable before injection or other administrative technique in the body of a patient. Preferably, the tumor-dispersible radioactive material is injected or otherwise administered by commonly known methods such as intravenous injection or drip, directly into or proximate to a volume of treatment such as a cancerous tumor. Examples of these radioactive dispersible tumor materials include radioisotopes that are connected to or encompass or circumscribe in organic or inorganic microspheres, mycelia or nanoparticles or are solubilized using chelates or other organic or inorganic agents. It is well known in the art that these materials, when administered locally in, in or near diseased tissue, such as a cancerous tumor, may exhibit prolonged tissue retention with biological half-lives in the range of several hours to several weeks. The isotropic radiation 48 emitted by the dispersible radioactive material, 42 activates a portion of the tumor-specific radio sensitizer 50 that is present within a radiation interaction volume 52 (defined by the penetration distance of this radiation 48 within the tumor environment). / radio sensitizer) to produce a localized treatment zone 56. Since any radiation 58 that reaches beyond this localized treatment zone 56 is of sufficient intensity to substantially activate the radio sensitizer 60 present outside the localized treatment zone 56, the localized treatment zone 56 is surrounded by a non-therapeutic or untreated volume 62. Thus, in most cases a single entity of the tumor-dispersible radioactive material 42, such as a simple radioactive particle or nanoparticle, will be insufficient for the complete treatment of the entire volume of desired treatment 46.

The present invention overcomes this apparent disadvantage through the use of a plurality of sources within the treatment volume. Preferably, the radiation sources are distributed substantially evenly within the volume of tissue, such that the zones of this source are contiguous or overlapping and there is a sufficient number of radiation sources, such that substantially all of the The volume of tissue to be treated lies within at least one treatment area. The radioactive sources can also be distributed within the volume of treatment, such that the areas of tissue to be treated that reside at the outer borders of a treatment zone, such as for example the outer third of the area, are within two. or more areas to ensure better radiation treatment. In other words, the treatment zones overlap, and some of the tissue volume lies within two or more zones. Preferably, the radio sensitizer and radioactive dispersible tumor material (this material is also known as a radiopharmaceutical agent) are administered to a patient (directly in or in proximity to the tumor or other diseased tissue) by (1) simple injection or other similar supply technique of a mixed solution of each, or (2) by sequential administration of each (by simple injection or other similar delivery technique). It is further preferred that this administration be carried out using a concentration and volume of radio sensitizer material selected to deliver a dose of more than one nanogram of radio sensitizer per kilogram of diseased tissue (i.e. = ng / kg), but not more than about 10 grams of radio sensitizer per kilogram of diseased tissue (ie <10 g / kg), these doses are chosen to produce a cytotoxicity sufficiently localized in the diseased tissue between radiation while avoiding induction of specific or systemic toxicity or cytotoxicity of the material alone. Still further, it is further preferred that this administration be performed using a concentration and volume of radioactive material selected to deliver a dose to the tissue within a select volume greater than about 1 milliGray (ie = 1 mGy) but not greater than about 1000 Gray. (ie <1000 Gy), with a preferred dose in the range of about 0.1 Gy to 100 Gy. The dose is chosen to produce sufficient localized activation of the radio sensitizer while avoiding induction of non-specific or systemic damage from the coated material alone.

A concerted supply of materials can be facilitated by using radio sensitizer and radioactive dispersible tumor materials that have similar biological or chemical and dimensional properties (such as hydrophilicity, or lipophilicity), since the dispersion of these agents will tend to occur in a similar manner, resulting in in a substantially uniform distribution of both the radio sensitizer and the radioactive dispersible tumor material at the treatment site. In contrast to previous methods, such an approach has a number of distinct advantages. Since the administration of radio sensitizer and radioactive material can be performed by injection or other simple administrative techniques, the complexity of the procedure and apparatus required is greatly reduced with respect to those required for application of radiation using external sources or implantable sources. This administration is possible using a single step wherein the radiosensitizer and radioactive material are administered together in a mixed formulation. Alternatively, a simple two or more step administration procedure may be employed. In this method, materials are administered in a separate stepwise fashion, for example to allow a component to achieve a uniform distribution before administration of the second component, or wherein multiple doses of one or more components, are required to maintain a therapeutic level, for example to compensate for radioactive decay or other loss of one or more components in a treatment volume. In addition, if radio sensitizers and radioactive materials that are capable of rapid deterioration or natural body release are used, the complexity of the follow-up procedure is also greatly reduced, since by destroying the tumor these agents will decompose or otherwise be released. of the triple tumor and the patient by natural processes. Therefore, unlike brachytherapy, there will be no residual material left on the site (such as brachytherapy needles that may require surgical removal). In some specialized cases, it may be necessary to more carefully couple the supply of radio sensitizer and radio pharmaceutical agent in a more refined form. According to a further embodiment of the present invention, methods and agents for achieving this coupling are illustrated in Figures 3A, 3B and 3C. In general, the agent includes a radio sensitizer component and an ionizing radiation source component combined to form an injectable treatment agent. More specifically, Figure 3A illustrates a linkage of one or more radio sensitizer portions 70 such as, for example, one of the radio sensitizers discussed above and one or more radioactive moieties 72 using for example covalent bonding or other chemical or physical mechanisms 74, to produce a conjugated radio-sensitizing agent 76. This covalent linkage can consist, for example, of a covalent bond between a radioactive complexed ligand and an organic radio sensitizer. This conjugate agent 76 ensures that the radio sensitizer and radiation source are supplied together at the appropriate stoichiometry, in a manner similar to that discussed previously. Preferably, multiple entities of these conjugated agents are administered to the volume or region of the treatment as discussed above. The present invention is not limited to a specific radioactive position. Specific examples of radioactive portions that can be used in the present invention include various radioisotopes and chemical derivatives of these radioisotopes, including those of aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium , rhodium, ruthenium, sulfur, technetium, thallium, yttrium and other radioactive elements, compounds or materials capable of producing a-ß- ?, X rays or other high-energy or ionizing radiation. An alternate embodiment, illustrated in Figure 3B, utilizes (a) a radio sensitizing portion 70, such as, for example, those previously discussed, connected to a biological chemical target portion 78 to produce a sensitizer conjugate 80, and (b) a portion radioactive 72, such as for example those previously discussed, connected to a similar biological or chemical target portion 78, to produce a conjugated radio 62. The delivery of the sensitizer conjugate 80 and the conjugated radio 82, in a manner similar to that discussed previously, for example by injection, either together or sequentially, they facilitate a combined uniform supply of both elements to the desired treatment site, based on the specificity of the target portions 78 for a diseased site. A further alternate embodiment of the present invention illustrated in Figure 3C, includes one or more radio sensitizing portions 70 and one or more radioactive portions 72, such as, for example, the portions discussed previously, in a delivery vehicle 82.

Examples of these delivery vehicles include a mycelium, liposome or nanoparticle that is formed using methods commonly available in the art. This encapsulated agent 84 can be designed to deliver its contents 70 and 72 to a specific treatment area or cellular structure, such as cell membranes to further enhance the improved dose efficiency, as described in the co-pending US patent application. No. 09 / 216,787 here incorporated by reference. Specific examples of the biological or chemical target portions as described with reference to Figures 3A and 3B, include DNA, RNA, amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors or complexing agents, protein receptors or complexing agents, receptors of lipids, or complexing agents before, chelators, encapsulating vehicles, nanoparticles, aromatic or aliphatic hydrocarbons of short or long chain, including those containing aldehydes, ketones, alcohols, esters, amides, amines, nitriles, azides or other hydrophilic or hydrophobic portions . Accordingly, a preferred embodiment of the present invention is to combine the delivery of an efficient radio sensitizer, such as for example Rose Bengal, and a radioactive, tumor dispersible material, such as, for example, rhenium-188 (188R), as a injectable mixture in diseased tissue, such as a cancerous tumor. 188Re is a gamma emitter produced from a generator (155 keV), which is easily packaged in the form of nanoparticles with a biological half-life of approximately one week. This gamma energy is easily absorbed by iodine atoms contained in Rose Bengal, which transform this energy into a therapeutically active form (such as Auger electrons and other secondary low-energy emissions) that are capable of easy tumor destruction. Since Rosa Bengala will tend to concentrate on cell membranes, the energy released from this target material will ideally be suitable for stimulating cell necrosis as a consequence of acute membrane damage resulting from the interaction of therapeutic energy with these structures. In addition, the radiosensitizing agent present in the cytoplasm will be conveniently arranged to facilitate damage to cellular genetic material and other cellular structures, as a consequence of similar secondary emission mechanisms. In addition, because radio sensitizer and radioisotope are rapidly released from the body, the complexity of any necessary follow-up procedures is minimal, since the body will tend to eliminate the residual radio sensitizer, radioactive material and tumor product destroyed by natural means. This description has been offered for illustrative purposes only and is not intended to limit the invention of this application, which is defined in the following claims. For example, it will be clear to those of ordinary skill in the art that the objective described herein for the specific example of halogenated xanthenes can be adapted or otherwise applied to other radio dense materials, including conventional radio sensitizers. Accordingly, the scope of the present invention is not as described in detail previously, but as set forth in the appended claims.

Claims (50)

1. CLAIMS 1. - A method for treating a selected volume of tumor tissue, the method is characterized in that it comprises: distributing a radio sensitizer within the volume; and distributing a plurality of sources of ionizing radiation within the volume, each radiation source produces a radiation treatment zone; wherein the radio sensitizer is a halogenated xanthene.
2. 2. - The method according to claim 1, characterized in that the radio sensitizer is evenly distributed through the tissue volume.
3. 3. - The method according to claim 1, characterized in that the sources of radiation are evenly distributed through the volume of the fabric so that the radiation treatment areas are evenly distributed through the tissue volume.
4. 4. - The method according to claim 1, characterized in that each of the radiation treatment areas overlaps at least one other treatment area.
5. 5. - The method according to claim 1, characterized in that the radio sensitizer is attached to a target portion to define a conjugated agent and the radiation zones are bound to the target portion to define another conjugated agent.
6. 6. The method according to claim 1, characterized in that the radio sensitizer and radiation sources are encapsulated in a delivery vehicle.
7. 7. The method according to claim 1, characterized in that the distribution of a radio sensitizer and the distribution of the sources of ionizing radiation are carried out sequentially administering the radio sensitizer and sources of ionizing radiation.
8. 8. - The method according to claim 1, wherein the radio sensitizer, when distributed, is conjugated with the tissue.
9. 9. Method according to claim 1, characterized in that the source of radiation, when distributed, is conjugated with the tissue.
10. 10. The method according to claim 1, characterized in that it also comprises introducing the radio sensitizers systemically.
11. 11. The method according to claim 1, characterized in that it further comprises introducing the radio sensitizer directly to the selected tissue volume.
12. 12. - The method according to claim 11, characterized in that the distribution of the radio sensitizer occurs after the introduction of the radio sensitizer.
13. 13. - The method according to claim 11, characterized in that the distribution of the radio sensitizer occurs during the introduction of the radio sensitizer.
14. 14. - The method according to claim 1, characterized in that it further comprises injecting the radio sensitizer at a site close to the select volume of the tissue.
15. 15. The method according to claim 14, characterized in that the distribution of the radio sensitizer occurs after the injection of the radio sensitizer.
16. 16. The method according to claim 14, characterized in that the distribution of the radio sensitizer occurs during the injection of the radio sensitizer.
17. 17. The method according to claim 1, characterized in that it also comprises introducing the sources of ionizing radiation directly into the select volume of the tissue.
18. 18. The method according to claim 17, characterized in that the distribution of the radiation sources occurs after the introduction of the radiation sources.
19. 19. The method according to claim 19, characterized in that the distribution of the radiation sources occurs during the introduction of the radiation sources.
20. 20. The method according to claim 1, characterized in that the radio sensitizer is activated uniformly through the selected volume of tissue.
21. 21. The method according to claim 1, characterized in that the source of radiation is a radioactive material dispersible tumor.
22. 22. The method according to claim 1, characterized in that the halogenated xanthene is selected from the group consisting of Rose Bengal, Floxin B, Erythrosin B, Eosin Y, other highly brominated halogenated xanthenes, other highly iodinated halogenated xanthenes and 4, 5,6,7-tetrabromoerythrosine.
23. 23. - The agent according to claim 1, characterized in that the radio sensitizer has a concentration between about 1 ng to 10 g of radio sensitizer per kg of tissue.
24. 24. - The method according to claim 1, characterized in that the source of ionizing radiation provides a dose within the treatment zone of between about 1 mGy and 1000 Gy.
25. 25. The method according to claim 24, characterized in that the dose is between approximately 0.1 Gy and 100 Gy.
26. 26. The method according to claim 1, characterized in that the source of radiation is chosen from the group consisting of radio isotopes of aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and zinc.
27. 27. The method according to claim 1, characterized in that the halogenated xanthene includes an aggregated or connected target portion, selected from the group consisting of deoxyribonucleic acids (DNA), ribonucleic acid (RNA), amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors, carbohydrate complexing agents, protein receptors, protein complexing agents, lipid receptors, lipid complexing agents, chelators, short chain aliphatic hydrocarbons, short chain aromatic hydrocarbons, long chain aliphatic hydrocarbons , long-chain aromatic hydrocarbons, aldehydes, ketones, alcohols, esters, amides, amines, nitriles and azides.
28. 28. The method according to claim 5, characterized in that the target portion is chosen from the group consisting of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), aminoo acids, proteins, antibodies, ligands, haptens, carbohydrate receptors, carbohydrate complexing agents, protein receptors, protein complexing agents, lipid receptors, lipid complexing agents, chelators, short-chain aliphatic hydrocarbons, short-chain aromatic hydrocarbons, long-chain aliphatic hydrocarbons, long-chain aromatic hydrocarbons, aldehydes , ketones, alcohols, esters, amides, amines, nitriles and azides.
29. 29. - An agent for treatment of tissue, the agent is characterized in that it comprises: a radio sensitizer component and a source component of ionizing radiation, the radio sensitizer component and the radiation source component combine to define an injectable treatment agent, wherein the Radio sensitizer is a halogenated xanthene.
30. 30. The agent according to claim 29, characterized in that the agent is in liquid form.
31. 31. The agent according to claim 29, characterized in that the agent is in the form of a gel.
32. 32. The agent according to claim 29, characterized in that the radio sensitizer component and the radiation source component are conjugated.
33. 33. The agent according to claim 29, characterized in that the radio sensitizing component and the radiation source component are located in a delivery vehicle, to define an encapsulated agent.
34. 34. The agent according to claim 29, characterized in that the ionizing radiation source component is a radioactive, tumor dispersible material. The agent according to claim 34, characterized in that the radioactive dispersible tumor material is selected from the group consisting of radioisotopes connected to or encompassed or circumscribed in microspheres, mycelia, organic or inorganic colloidal nanoparticles, or solubilized using chelates, agents organic and inorganic agents. 36.- The agent according to claim 29, characterized in that the halogenated xanthene is selected from the group consisting of Rose Bengal and its derivatives, Floxin B and its derivatives, Erythrocin B and its derivatives, Eosin Y and its derivatives, highly brominated halogenated xanthenes and their derivatives, highly iodinated halogenated xanthenes and their derivatives and 4, 5, 6, 7-tetrabromoerythrosin and its derivatives. 37. The agent according to claim 29, characterized in that the radio sensitizer component has a concentration of between about 1 ng to 10 g of radio sensitizer per kg of tissue. 38. The agent according to claim 29, characterized in that the source component of ionizing radiation provides doses within the treatment zone of between about 1 mGy and 1000 Gy. 39.- The agent according to claim 38, characterized in that the dose is between approximately 0.1 Gy and 100 Gy. The agent according to claim 29, characterized in that the radiation source component is a radioactive portion selected from the group. consisting of aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and zinc. 41. The agent according to claim 29, characterized in that the radio sensitizer component and the radiation source component are located in a delivery vehicle to define an encapsulated agent. 42. The agent according to claim 41, characterized in that the delivery vehicle is selected from the group consisting of a mycelium, liposome and nanoparticle. 43. An agent for the treatment of tissue, the agent is characterized in that it comprises: a conjugate agent comprising a radio sensitizer attached to a target portion; a second conjugate agent comprising a radiation source linked to a target portion; and wherein the radio sensitizer is a halogenated xanthene. 44. The agent according to claim 43, characterized in that the target portion is selected from the group consisting of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors, carbohydrate complexing agents, protein receptors, protein complexing agents, lipid receptors, lipid complexing agents, chelators, short-chain aliphatic hydrocarbons, short-chain aromatic hydrocarbons, long-chain aliphatic hydrocarbons, long-chain aromatic hydrocarbons, aldehydes , ketones, alcohols, esters, amides, amines, nitriles and azides. 45. The agent according to claim 44, characterized in that the source component of radiation is a radioactive material dispersible from tumor. 46. The agent according to claim 45, characterized in that the radioactive dispersible tumor material is selected from the group consisting of radioisotopes connected to or encompassed in microspheres, mycelia, nanoparticles and organic or inorganic colloids, or solubilized using chelates, organic agents and inorganic agents. 47.- The agent according to claim 43, characterized in that the halogenated xanthene is selected from the group consisting of Rose Bengal and its derivatives, Floxin B and its derivatives, Erythrocin B and its derivatives, Eosin Y and its derivatives, halogenated xanthenes. highly brominated and their derivatives, highly iodinated halogenated xanthenes and their derivatives and 4, 5, 6, 7-tetrabromoerythrocin and its derivatives. 48. The agent according to claim 43, characterized in that the source component of radiation is a radioactive portion selected from the group consisting of aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus. , radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and zinc, 49.- A method for treating a selected volume of tumor tissue, characterized in that it comprises the steps of: administering a dose of radio sensitizer to a patient, a portion of the dose of radio sensitizer is substantially uniformly retained through the volume of tissue; and locally administering a plurality of radiation sources at a site close to or in the tissue volume, the radiation sources are distributed through the tissue volume, to produce a substantially uniform radiation through the volume of tissue; and wherein the radio sensitizer is a halogenated xanthene. 50.- The method according to claim 1, characterized in that the distribution of a radio sensitizer and the distribution of ionizing radiation sources are carried out by the simultaneous administration of the radio sensitizer and the sources of ionizing radiation.