CN1337886A - Method for improved radiation therapy - Google Patents
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- CN1337886A CN1337886A CN00803059A CN00803059A CN1337886A CN 1337886 A CN1337886 A CN 1337886A CN 00803059 A CN00803059 A CN 00803059A CN 00803059 A CN00803059 A CN 00803059A CN 1337886 A CN1337886 A CN 1337886A
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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
Background of invention
The present invention relates to be used for the designated volume of tissue such as abnormal cell proliferation or malignant tissue are carried out radiocurable method and composition.Specifically, the present invention relates to novel method, this method is that radiosensitizer and a large amount of ionization radioactive source are distributed in the tissue volume substantially, to produce the area for treatment that evenly is dispersed throughout in the tissue volume.The present invention also is particularly related to the new medicament that is used for the treatment of described tissue, comprising by radiosensitizer and ionization radioactive source in conjunction with and the injectable healing potion that forms.
As everyone knows, can to adopt as ionizing radiation be that X-ray therapy is treated to the abnormal cell proliferation that occurs in the cancer.In X-ray therapy (typically but do not use 1 kilo electron volt or more high-octane electromagnetic radiation), can adopt external radiation source or place needs the radioactive source of treated tissue inside to come divergent-ray not essentially.A known radiotherapeutic shortcoming is that the health tissues around the subject main site of butt joint can cause collateral damage.Therefore, a subject matter facing of radiotherapy is exactly optionally to transport the ray of therapeutic dose to need treated tissue such as cancerous tumour.A kind of technology of locating effect of radiation is to combine with the ray of being launched with radiation sensitization or radiopaque ray sensitizing agent.When these medicaments were introduced organizing of need treating, they can strengthen the effect with ray in the tissue of sensitizing agent treatment, and the generation radiological dose strengthens (DE) effect in tumor.
Yet the use of sensitizing agent only is a progress, but is not the in-problem mode that satisfactorily resolves of X-ray therapy.Still have many problems deserving of attention when adopting this method, particularly how the tissue or the treatment volume of need treatment imposed uniform treatment.For example, after giving radiopaque ray sensitizing agent, therapeutic radiation dosage always is subjected to the retardance of the treatment volume of radiosensitizer shielding to evenly transporting of whole treatment volume.
More particularly, when using external radiation, emit the radioactive source of ray beyond health, and the radiosensitizer that approaches most in the treated tissue of radioactive source may cause shielding or retardance to the tissue of ionizing ray end.Therefore, only the part treated tissue obtains effective radiological dose.
Similarly, when the tip of narrow radioactive source such as radioactive probe or tinsel or band directly being introduced or approach in the need treated tissue (being commonly referred to the short range X-ray therapy), the radiosensitizer that approaches radioactive source most can cause shielding to the required radiological dose of remainder of tissue.Consequently can not provide uniform treatment to tissue volume such as tumor.
Therefore, an object of the present invention is to improve tumor etc. is organized the radiocurable uniformity of designated volume.
Another object of the present invention provides method and the medicament that is used for need treated tissue volume is carried out more homogeneous radiation treatment.
The invention summary
The present invention relates to organize the Therapeutic Method of designated volume.This method comprises radiosensitizer is distributed in the tissue volume, and a large amount of ionization radioactive sources are distributed in the tissue volume, and each radioactive source all can produce a radiotherapy zone.Distribution of radiation make the area for treatment of a large amount of radioactive sources be distributed in equably in the described tissue volume usually, and the tissue of all described designated volumes is arranged at least one radiotherapy zone basically in tissue volume.
In a preferred embodiment of the present invention, radiosensitizer and/or radioactive source are uniformly distributed in the designated volume basically, so just provide treatment more uniformly to the designated volume interior tissue.According to another aspect of the present invention, each area for treatment and at least a other area for treatment are overlapping, and can guarantee like this provides more effective treatment to the tissue in the designated volume.
According to other aspects of the present invention, the distribution of radiosensitizer and ionization radioactive source can successively or be carried out simultaneously, the designated volume that together injects or approach to organize for example, and on the other hand can successively give radiosensitizer and ionization radioactive source and makes their realize distributing.
According to another aspect of the present invention, for avoid to health or designated volume beyond the undue influence of its hetero-organization, the area for treatment of preferred radioactive source does not exceed the designated volume of described tissue substantially.
The present invention also relates to the medicament of treated tissue on the other hand.Preferably, this medicament comprises a kind of radiosensitizer and a kind of ionization radioactive source component, radiosensitizer component and ionization radioactive source component in conjunction with and form injectable healing potion.This medicament can be any suitable form, but the present invention is preferably liquid or gel.Simultaneously, but also conjugation and form injectable medicament of radiosensitizer and ionization radioactive source.
Following claims and detail specifications will carry out some elaborations and description to many aspects of the present invention.
The accompanying drawing summary
Fig. 1 a represents to have earlier the shielding embodiment of Therapeutic Method to area for treatment inside and end portion.
What Fig. 1 b represented to adopt the inner radiation source has the shielding embodiment of Therapeutic Method to the area for treatment end portion earlier.
But Fig. 2 a need to represent single tumor dispersivity radioactive substance and the bonded effect of tumour-specific radiosensitizer in the treated tissue.
Fig. 2 b is a preferred embodiment of the present invention, but wherein the tumor dispersivity radioactive substance in Fig. 2 a treated tissue is a solid polymer composite.
Fig. 3 a is one embodiment of the invention, wherein radiosensitizer component and radioactive component bonding and form a kind of sensitizing agent-radioactivity conjugation medicament.
Fig. 3 b is one embodiment of the invention, and wherein conjugated radiosensitizer combines with the targeting component and forms the sensitizing agent conjugate; Combine formation radiation conjugation medicament with the targeting component with the conjugation radioactive component,
Fig. 3 c is one embodiment of the invention, radiosensitizer component and radioactive component in the expression drug administration carrier.
Detailed description of the preferred embodiments
Fig. 1 a and 1b show that there is the problem of alpha ray shield or retardance in prior art.Particularly, Fig. 1 a represents to treat the embodiment of internal volume and tip shielding 10 partly.In this embodiment, a kind of radiopaque sensitizing agent 16 is dispersed throughout in treatment volume 18 as carcinous or the malignant tumor.When with external radiation source 14 divergent-rays 12, ray 12 is preceding at the sensitizing agent (22) that arrival is positioned at the external radiation source end, and its most of sensitizing agent (20) that is just approached most external radiation source 14 has basically absorbed.Like this, the ray of treatment inside of volume 18 and end portion 12 is with regard to conductively-closed, and the activation usefulness that surpasses the terminal sensitizing agent 22 of some ray penetration range 24 has just obviously reduced.This oneself's shielding causes the inhomogeneities of treatment, wherein most of or whole activity occur over just in Asia-volume 26, and this volume mainly is to be in the part (being the radioactive source-target position separation in ray penetration range 24 scopes) that approaches radioactive source 14 in the treatment volume 18 most.Even adopt the number of ways administration, can this type shielding take place in the inside of treatment volume also, so just reduced the effectiveness of whole therapy.
Another embodiment of shielding 30 sees Fig. 1 b, has wherein adopted closed (contained) inner radiation source as using in brachytherapy.Shown in Fig. 1 b, a kind of radiopaque sensitizing agent 16 is distributed in the treatment volume 18 with basic form uniformly.When with inner radiation source 32 divergent-rays 12, can produce shielding to the end portion of treatment volume 18.Ray 12 is before the sensitizing agent that arrives inner radiation source 36 ends, and its most of sensitizing agent that is just approached most inner radiation source 34 has basically absorbed.Like this, the terminal sensitizing agent 36 that surpasses some effective rays penetration range 24 with regard to conductively-closed and also its activation usefulness also obviously reduce.This oneself's shielding causes the inhomogeneities of treatment, wherein most of or whole activity occur over just in Asia-volume 38, and this volume mainly is to be in the part (being the radioactive source-target position separation in effective penetration range 24 scopes of ray) that approaches inner radiation source 32 in the treatment volume 18 most.
Compare with prior art, the inventive method can provide more uniform radiotherapy to organizing designated volume such as pernicious lump or tumor.
Shown in Fig. 2 a and 2b, usually the inventive method comprises radiosensitizer 44 is distributed in the volume 46 that needs treated tissue, and a large amount of ionization radioactive sources 42 are distributed in the described volume.Before other materials shield inadequately, block or weaken in by sensitizing agent 44, tissue or tissue, each radioactive source 42 all can be to all directions divergent-ray in effective radius, thereby form area for treatment 56, ray combines with radiosensitizer in this zone and required radiological dose enhancement effect is provided.Radioactive source is dispersed throughout in the tissue volume, makes organizing in all treatment volumes all be arranged in one or more area for treatment basically.Preferably, radiosensitizer and radioactive source are distributed in the designated volume of tissue basically equably, thereby more all even efficient emission therapy can be provided specific tissue volume.
Shown in Fig. 2 b, in a preferred embodiment of the invention, but the solid polymer composite of the tumor dispersivity radioactive substance 42 of compound radioactive grain or form of nanoparticles is placed the treatment volume.But increase the concentration of tumor dispersivity radioactive substance 42 entities in the treatment volume 46, make the solid polymer composite that is in these materials in the area for treatment 56 overlapping, thereby need realize effectively treatment 64 in the treatment volume 46 whole.But tumor dispersivity radioactive substance once distribute, preferably be distributed in equably basically in the tumor (this distribution from one to a plurality of main administrations site can by disperse normally, passive dispersal mechanism is implemented in dilution or other element bodies), just can be used as homodisperse radioactive source, they can produce basic ray uniformly in gross tumor volume.And, use this dispersal mechanism to transport minimum effective radiological dose to the health tissues beyond the treatment volume.This uniform ray can activate the described radiosensitizer that is dispersed throughout in the gross tumor volume more equably (between radioactive source and target spot, but be tumor dispersivity radioactive substance discussed below and radiosensitizer), and a kind of method that radiotherapy dosage in the X-ray therapy is transported to more simple and efficiently whole tumor is provided.This shielding to arbitrary given entity 42 weakens effect and greatly simplifies the budget of radiological dose and transport.As mentioned above, because tumour-specific radiosensitizer 44 only is in the volume 46 that needs treatment basically, exceeding needs that the part 66 of any ray interaction volume 56 can not produce tangible collateral damage to radiating adjacent volume 68 beyond the treatment volume 46.Similarly, as described above, by to intratumor injection or other similar medicine-feeding technologies such as nearly vein or lymph injection, but can easily transport the solid polymer composite of this tumor dispersivity radioactive substance 42.
The designated volume of treatment volume or tissue can be any particular organization that is used for the treatment of.Typical case but not exclusively, the tissue that treat can be can be with the radiocurable tissue that the proliferative cell growth has taken place of ionization.Although this cell proliferation can be benign, can expect that the present invention is having very big application aspect the malignant tissue of treatment tumor form, for example the lump of cancerous tumour or other malignant tumor or illing tissue such as cyst, polyp or abscess.
The specific radiosensitizer that is adopted during the present invention is not limited to, the sensitizing agent particular instance that can adopt comprises the halogenation xanthene and the derivant thereof of multiple radiation sensitization, for example rose-red and derivant, phloxin B and derivant thereof, Erythrosin B and derivant, eosin W or W S and derivant thereof, and height bromination or height iodate xanthene and derivant thereof, comprise 4,5,6,7-tetrabromo Erythrosin; Multiple x-ray contrast agent is as Omnipaque
TM(iohexol), Omniscan
TM(gadodiamide), WIN8883 (diatrizoic acid), iodamide and ethiodized Oil, and contain the medicament of a large amount of radiation sensitization elements or component such as iodine, bromine, chlorine, barium, bismuth, boron, gold, silver, platinum, ferrum, gadolinium, dysprosium and tantalum; Iodate BrdU and bromination BrdU and related agents; Multiple halogenation nucleic acid and DNA part and intercalator comprise multiple based on the acridine and the imidazoles medicament that replace; The biological reductant that multiple nitroimidazole is relevant with other; Misonidazole and related agents; Etanidazole and related agents; Pimondazole and relevant piperidine derivative; Aziridine and related agents; Cyclophosphamide and related agents; Nitroso ureas and related agents; L-phenylalanine mustard and related agents; Cis-Platinum compound and related agents; With amycin and related agents.The present invention preferably adopts the tumour-specific radiosensitizer, as the halogenation xanthene.More preferably the tumour-specific radiosensitizer is rose-red.
Usually, radiosensitizer is introduced the treatment volume, as passing through intravenous administration, direct injection or similar routine techniques by the whole body administration.More preferably, this kind administration comprises that direct injection or other can introduce medicine or need to approach the medicine-feeding technology of treated tissue.Adopt this type of medicine-feeding technology to give above-mentioned radiosensitizer, can make the radiosensitizer of treatment effect level in need treatment volume, be detained a few hours to several weeks.Like this, comprise that through dispersion, dissolving or other passive equilibrium or concentration process selectivity absorbs, radiosensitizer just can be uniformly distributed in basically to be needed in the treatment volume.
The inventive method also comprises the step of a large amount of ionization radioactive sources that distribute.The present invention does not limit the quantity of ionization radioactive source, but estimates to use not only a kind of ionization or other high energy radioactive source.But be used for this kind radioactive source example of the present invention and be tumor dispersivity radioactive substance as discussed below.Yet the present invention is not limited to this kind radioactive substance, but tumor dispersivity radioactive substance of discussing below and radioactive component and other similar material all can adopt.The radioactive source that preferably has one or more is in the treatment volume.And, as described below, preferably have a large amount of this kind distribution of radiation in the treatment volume.
Particularly, the effect 40 of single radioactive source has been described, but has been in the treatment volume, wherein tumour-specific radiosensitizer 44 uniform distribution and being contained in the treatment volume 46 basically as described above in a large number as tumor dispersivity radioactive substance 42 as Fig. 2 a." but tumor disperse " refers to be easy to disperse in treatment volume such as tumor.Typically; but tumor dispersivity radioactive substance can be to make liquid, gel with dissolving or solubilising or dispersive form; but or discrete form or preparations such as other fine grained formed by radioactive substance or colloidal suspension, can by injection or other medicine-feeding technology is stable introduce in the patient body.The preferred employing injected or other conventional medication such as intravenous drip or injection, but tumor dispersivity radioactive substance is directly introduced or approached to treat in volume such as the cancerous tumour.
But the example of this kind tumor dispersivity radioactive substance comprises and adheres to or be encapsulated in organic or inorganic microsphere, micelle or the nano-particle, or with the radiosiotope of chelate, organic reagent and inorganic reagent solubilising.Well known in the art: when with this kind material topical administration or when approaching ill volume such as cancerous tumour, it can prolong delay in described tissue, and its biological half-life can reach several hours to several weeks.
But the isotope ray 48 of tumor dispersivity radioactive substance 42 emissions, activated a part of tumour-specific radiosensitizer 50 of (determining) in the volume 52 that is present in actinism, so just formed a locating therapy zone 56 by the penetration range of ray 48 in tumor/radiosensitizer environment.Because the enough intensity that can not produce any ray 58 that exceeds beyond the locating therapy zone 56 activates the radiosensitizer 60 beyond the locating therapy zone 56, then locating therapy zone 56 is surrounded by non-therapeutic or non-treatment volume 62.Like this, as a rule, but the single entities of tumor dispersivity radioactive substance 42 such as single radioactive grain or nano-particle provide treatment completely with being not enough to the whole volume 46 of treatment that needs.
The present invention has overcome the use open defect that a large amount of radioactive source brought in the treatment volume.Preferably, radioactive source is uniformly distributed in the volume of tissue substantially, makes the area for treatment of each radioactive source be in contact with one another or overlapping, and the radioactive source of capacity makes all treated tissue volumes be at least one area for treatment basically.Radioactive source also can be distributed in the treatment volume, makes to be in outer as treated tissue zone zone outer 1/3rd of area for treatment and to be in two or more zones and so that guarantee better enough radiotherapies to be arranged.In other words, overlapping some tissue volume that make of area for treatment are in two or more zones.
Preferably, but radiosensitizer and tumor dispersivity radioactive substance (radiopharmaceutical as is known) can be through following method afford patient (directly giving or approach tumor or other illing tissue): (1) simple injection or other the similar technology that gives the two mixed solution, or (2) respectively order give (simple injection or other similar medicine-feeding technology).More preferably the concentration and the volume of radiosensitizer material are selected, make dosage (promptly 〉=ng/kg) but be lower than that about the 10g radiosensitizer/kg illing tissue (promptly≤g/kg) greater than about 1ng radiosensitizer/kg illing tissue, select this dosage can when radiation, produce enough local cells toxicity, non-specific or general toxicity or the cytotoxicity of having avoided radioactive substance to bring out again simultaneously to described illing tissue.In addition, more preferably the concentration and the volume of radioactive substance are selected, made the dosage organize greater than about 1 milligray (milligray promptly 〉=1) but be lower than about 1000 gray(Gy)s (gray(Gy) promptly≤1000), be preferably about 0.1-100 gray(Gy).Select this dosage to produce enough activation, avoided radioactive substance to bring out non-specific again simultaneously or the general damage radiosensitizer.
But utilize radiosensitizer and tumor dispersivity radioactive substance to have similar space and chemistry or biological nature (as hydrophilic and lipotropy), be easy to realize the cooperativing medicine-feeding of the two, because the breaking up of the branch of this type of medicament is carried out in a similar fashion, but so radiosensitizer and tumor dispersivity radioactive substance all can obtain distributing uniformly substantially in the treatment site.
Compare with method is arranged earlier, this kind method has many tangible advantages.Can give radiosensitizer and radioactive substance through injection or other simple medicine-feeding technologies, compare, the complexity of method and the requirement of equipment just reduced widely with the method for using external radiation source or implantable radioactive source.When radiosensitizer and radioactive substance are mixed in the same preparation, can adopt a step administration.In addition, also can adopt simple two or the rapid administration of multistep.In the method, the mode administration of can be stage by stage or separating, for example can be with first kind of component uniform distribution before giving second kind of component, or the multiple dose form that adopts one or more components to be to keep treatment level, for example can compensate the radiation damping in the treatment volume or the unknown losses of one or more components.If radiosensitizer and radioactive material mass-energy is decay or remove naturally fast in vivo, so just reduced the complexity of subsequent treatment widely, because along with the destruction of tumor, medicament can decompose or dispose in tumor sites and patient's body through natural process.Therefore, different with brachytherapy, that this method can not cause in the site is residual (and the probe of brachytherapy need perform the operation remove).
Under some particular cases, be necessary to give radiosensitizer and radiopharmaceutical agent with further improved coupling manner.According to another embodiment of the present invention, method and the medicament that is used to obtain described coupling seen Fig. 3 a, 3b and 3c.This medicament generally comprise by radiosensitizer component and ionization radioactive source component in conjunction with and the injectable healing potion that forms.
More specifically, shown in Fig. 3 a, adopt,, thereby form a kind of sensitizing agent-radioactivity conjugation medicament 76 radiosensitizer component 70 and one or more radioactive component 72 bondings of one or more above-mentioned discussion as covalent bond or other Chemical Physics mechanism 74.For example, this covalent bonding can be made up of the radioactive component of part-complexation and the covalent bond between organic radiosensitizer.With being similar to the above-mentioned method of mentioning, this conjugation medicament 76 can transport the radiosensitizer and the radioactive source of suitable stoichiometric proportion.As mentioned above, preferably the solid polymer composite of this conjugation medicament is treated volume or zone.
The present invention is not limited to specific radioactive component.The particular instance that is used for radioactive component of the present invention comprises multiple radiosiotope and chemical derivative thereof, comprise aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and other radioelement, chemical compound, maybe can produce α-, β-, γ-, the material of χ-ray or other high energy or ionizing ray.
In another embodiment, shown in Fig. 3 b, adopt (a) to combine with chemistry or biological targeting component 78 and form sensitizing agent conjugate 80, combine with similar chemistry or biological targeting component 78 as the radioactive component in the above-mentioned example 72 with (b) and form radioactivity conjugate 82 as the radiosensitizer component 70 in the above-mentioned example.According to the specificity of disease sites targeting component 78, adopt to be similar to the above-mentioned method of mentioning as injection, give sensitizing agent conjugate 80 and radioactivity conjugate 82 simultaneously or sequentially, can make the site that two kinds of components are transported to together equably needs treatment.
In another embodiment of the present invention, shown in Fig. 3 c, contain aforesaid one or more radiosensitizer component 70 and one or more radioactive components 72 in the drug administration carrier 82.This drug carrier comprises micelle, liposome or the nano-particle with the known technology preparation.The medicament 84 of this kind through sealing is designed to and inclusions 70 and 72 wherein can be transported in specific area for treatment or cellularity such as the cell membrane, further improved the radiological dose enhancement effect, and be described as US 09/216787, is hereby incorporated by.
Shown in Fig. 3 a and 3b, the particular instance of chemistry or biological targeting component comprises DNA, RNA, aminoacid, protein, antibody, part, hapten, saccharide receptor or chelating agent, protein acceptor or chelating agent, lipid receptor or chelating agent, chelate, encapsulation vehicle, nano-particle, weak point or long-chain fat family and aromatic hydrocarbon, comprises aldehyde, ketone, alcohol, ester, amide, amine, nitrile and azide or other hydrophilic or hydrophobic components.
Therefore, in a preferred embodiment of the invention, but with a kind of contain efficient emission sensitizing agent such as rose-red and tumor dispersivity radioactive substance such as rhenium-188 (
188Re) injectable mixture is transported in illing tissue such as the cancerous tumour.
188Re is a kind of generation γ-radiation body (155 kilo electron volt) that is easy to be encapsulated as form of nanoparticles, an about week of its biological half-life.This γ-energy is easily by the iodine Atomic Absorption in rose-red, thereby changes into the form that therapeutic activity is arranged (as Auger electron and other low-energy Secondary Emission) that can destroy tumor.Can concentrate in cell membrane owing to rose-red, the energy that is discharged for the targeting material is very suitable for the irritation cell necrosis, because the treatment energy will cause acute membrane damage with the membrane structure effect.And the radiosensitizer in the Cytoplasm is through suitable disposal, and its Secondary Emission can cause damage with other cellularity by the pair cell hereditary material.In addition, radiosensitizer and radiosiotope can be removed in body fast, health can be disposed the tumor thing of residual radiosensitizer, radioactive substance and destroyed through natural method in addition, and so just the complexity with any required subsequent treatment is reduced to minimum.
Foregoing description only is used to illustrate, but determined the present invention is not limited to following claim.For example, those of ordinary skills obviously as can be seen, but be used for the targeting correct of the halogenation xanthene described in this particular instance or be used to comprise other radiation sensitizer of conventional planning sensitizing agent.
Therefore, scope of the present invention will be set forth in additional claim, and be not limited to foregoing description.
Claims (67)
1. the method for a treated tissue designated volume, this method comprises: a kind of radiosensitizer is distributed in this volume; And a large amount of ionization radioactive sources are distributed in this volume, each radioactive source all can produce a radiotherapy zone, is arranged at least one radiotherapy zone in this tissue volume basically in a organized way.
2. method as claimed in claim 1, wherein radiosensitizer is uniformly distributed in the volume basically.
3. method as claimed in claim 1, wherein distribution of radiation makes area for treatment be distributed in the tissue volume equably usually in the volume of tissue.
4. method as claimed in claim 1, wherein area for treatment and at least a other area for treatment are overlapping.
5. method as claimed in claim 1, wherein radiosensitizer and radioactive source mutually combine and form the conjugation medicament.
6. method as claimed in claim 1, wherein radiosensitizer combines with the targeting component and forms the conjugation medicament, and radioactive source combines another conjugation medicament of formation with the targeting component.
7. method as claimed in claim 1, wherein radiosensitizer and radioactive source are arranged in drug administration carrier and form a kind of encapsulation agents.
8. method as claimed in claim 5 is wherein injected the conjugation medicament or the volume that approaches to organize and radiosensitizer and ionization radioactive source are distributed simultaneously.
9. method as claimed in claim 1, the wherein volume that the conjugation medicament is organized in proper order and radiosensitizer and ionization radioactive source are distributed.
10. method as claimed in claim 1, wherein radiosensitizer when distributing with organize conjugation.
11. method as claimed in claim 1, wherein radioactive source when distributing with organize conjugation.
12. method as claimed in claim 1, wherein area for treatment does not exceed the designated volume of tissue basically.
13. method as claimed in claim 1 also comprises general introducing radiosensitizer.
14. method as claimed in claim 1 also comprises radiosensitizer is directly introduced in the designated volume of tissue.
15., carry out after wherein being distributed in introducing as the method for claim 14.
16., wherein be distributed between the introductory phase and carry out as the method for claim 14.
17. method as claimed in claim 1 also comprises radiosensitizer is expelled to and approaches most in the designated volume tissue.
18., carry out after wherein being distributed in introducing as the method for claim 17.
19., wherein be distributed between the introductory phase and carry out as the method for claim 17.
20. method as claimed in claim 1 also comprises direct introducing of radioactive source is organized in the designated volume.
21., carry out after wherein being distributed in introducing as the method for claim 20.
22., wherein be distributed between the introductory phase and carry out as the method for claim 20.
23. method as claimed in claim 1 wherein organizes designated volume to comprise the tissue of inappropriate cell proliferation.
24. method as claimed in claim 1, wherein radiosensitizer is activated in organizing designated volume basically equably.
25. method as claimed in claim 1, wherein ionization radioactive source is launched minimum effective ray beyond organizing designated volume.
26. method as claimed in claim 1, but wherein ionization radioactive source is a tumor dispersivity radioactive substance.
27. as the method for claim 26, but wherein tumor dispersivity radioactive substance is selected from and adheres to or be encapsulated in organic or inorganic microsphere, micelle, nano-particle and the colloid, or with the radiosiotope of chelate, organic reagent and inorganic reagent solubilising.
28. method as claimed in claim 1, wherein radiosensitizer is selected from the halogenation xanthene and the derivant thereof of radiation sensitization; X-ray contrast agent; The medicament that contains radiation sensitization element; Iodate BrdU and bromination BrdU and related agents; Halogenation nucleic acid and DNA part and intercalator; Based on the acridine that replaces and the medicament of imidazoles; Nitroimidazole and relevant biological reductant; Misonidazole and related agents; Etanidazole and related agents; Pimondazole and relevant piperidine derivative; Aziridine and related agents; Cyclophosphamide and related agents; Nitroso ureas and related agents; L-phenylalanine mustard and related agents; Cis-Platinum compound and related agents; With amycin and related agents.
29. method as claim 28, wherein the halogenation xanthene is selected from halogenation xanthene and the highly iodinating halogenation xanthene and the derivant thereof of rose-red and derivant, phloxin B and derivant thereof, Erythrosin B and derivant, eosin W or W S and derivant thereof, height bromination, comprise 4,5,6,7-tetrabromo Erythrosin.
30. as the method for claim 28, wherein x-ray contrast agent is selected from Omnipaque
TM(iohexol), Omniscan
TM(gadodiamide), WIN8883 (diatrizoicacid), iodamide and ethiodized Oil.
31., wherein radiate the sensitization element and be selected from iodine, bromine, chlorine, barium, bismuth, boron, gold, silver, platinum, ferrum, gadolinium, dysprosium and tantalum as the method for claim 28.
32. method as claimed in claim 1, wherein the concentration of radiosensitizer is about 1ng-10g/kg tissue.
33. method as claimed in claim 1, wherein ionization radioactive source provides the radiological dose of about 1 milligray-1000 gray(Gy) to area for treatment.
34. as the method for claim 33, wherein dosage is about 0.1-100 gray(Gy).
35. method as claimed in claim 5, wherein radioactive source is for being selected from following radioactive component: aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and zinc.
36. method as claimed in claim 6, wherein the targeting component is selected from DNA, RNA, aminoacid, protein, antibody, part, hapten, saccharide receptor, protein acceptor, lipid receptor, chelate, encapsulation vehicle, nano-particle is short or long-chain fat family and aromatic hydrocarbon and other hydrophilic or hydrophobic components and chelating agent.
37. as the method for claim 36, its short-and-medium or long-chain fat family and aromatic hydrocarbon comprise and are selected from one or more following chemical compounds: aldehyde, ketone, alcohol, ester, amide, amine, nitrile and azide.
38. method as claimed in claim 7, wherein drug administration carrier is selected from micelle, liposome and nano-particle.
39. the medicament of a treated tissue, this medicament comprises:
A kind of radiosensitizer component and
A kind of ionization radioactive source component,
Described radiosensitizer component and ionization radioactive source component in conjunction with and form injectable healing potion.
40. as the medicament of claim 39, wherein medicament is a liquid form.
41. as the medicament of claim 39, wherein medicament is a gel form.
42. as the medicament of claim 39, wherein radiosensitizer component and ionization radioactive source component are conjugated.
43. as the medicament of claim 39, wherein radiosensitizer component and ionization radioactive source component are arranged in drug administration carrier and form a kind of encapsulation agents.
44. as the medicament of claim 39, but wherein the ionization radioactive source component is a kind of tumor dispersivity radioactive substance.
45. as the medicament of claim 44, but wherein tumor dispersivity radioactive substance is selected from and adheres to or be encapsulated in organic or inorganic microsphere, micelle, nano-particle and the colloid, or with the radiosiotope of chelate, organic reagent and inorganic reagent solubilising.
46. as the medicament of claim 39, wherein radiosensitizer is selected from the halogenation xanthene and the derivant thereof of radiation sensitization; X-ray contrast agent; The medicament that contains radiation sensitization element; Iodate BrdU and bromination BrdU and related agents; Halogenation nucleic acid and DNA part and intercalator; Based on the acridine that replaces and the medicament of imidazoles; Nitroimidazole and relevant biological reductant; Misonidazole and related agents; Etanidazole and related agents; Pimondazole and relevant piperidine derivative; Aziridine and related agents; Cyclophosphamide and related agents; Nitroso ureas and related agents; L-phenylalanine mustard and related agents; Cis-Platinum compound and related agents; With amycin and related agents.
47. medicament as claim 46, wherein the halogenation xanthene is selected from halogenation xanthene and the highly iodinating halogenation xanthene and the derivant thereof of rose-red and derivant, phloxin B and derivant thereof, Erythrosin B and derivant, eosin W or W S and derivant thereof, height bromination, comprise 4,5,6,7-tetrabromo Erythrosin.
48. as the medicament of claim 46, wherein x-ray contrast agent is selected from Omnipaque
TM(iohexol), Omniscan
TM(gadodiamide), WIN8883 (diatrizoicacid), iodamide and ethiodized Oil.
49., wherein radiate the sensitization element and be selected from iodine, bromine, chlorine, barium, bismuth, boron, gold, silver, platinum, ferrum, gadolinium, dysprosium and tantalum as the medicament of claim 46.
50. as the medicament of claim 39, wherein the concentration of radiosensitizer is about 1ng-10g/kg tissue.
51. as the medicament of claim 39, wherein ionization radioactive source provides the radiological dose of about 1 milligray-1000 gray(Gy) to area for treatment.
52. as the medicament of claim 51, wherein dosage is about 0.1-100 gray(Gy).
53. as the medicament of claim 39, wherein the radioactive source component is for being selected from following radioactive component: aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and zinc.
54. as the medicament of claim 39, wherein radiosensitizer component and ionization radioactive source component are arranged in drug administration carrier and form a kind of encapsulation agents.
55. as the medicament of claim 54, wherein drug administration carrier is selected from micelle, liposome and nano-particle.
56. the medicament of a treated tissue, this medicament comprises:
Radiosensitizer combines a kind of conjugation medicament that forms with the targeting component; With
Radioactive source combines the second conjugation medicament that forms with the targeting component.
57. as the medicament of claim 56, wherein the targeting component is selected from DNA, RNA, aminoacid, protein, antibody, part, hapten, saccharide receptor, protein acceptor, lipid receptor, chelate, encapsulation vehicle, nano-particle is short or long-chain fat family and aromatic hydrocarbon and other hydrophilic or hydrophobic components and chelating agent.
58. as the medicament of claim 57, its short-and-medium or long-chain fat family and aromatic hydrocarbon comprise and are selected from one or more following chemical compounds: aldehyde, ketone, alcohol, ester, amide, amine, nitrile and azide.
59. as the medicament of claim 56, but wherein the ionization radioactive source component is a kind of tumor dispersivity radioactive substance.
60. as the medicament of claim 59, but wherein tumor dispersivity radioactive substance is selected from and adheres to or be encapsulated in organic or inorganic microsphere, micelle, nano-particle and the colloid, or with the radiosiotope of chelate, organic reagent and inorganic reagent solubilising.
61. as the medicament of claim 56, wherein radiosensitizer is selected from the halogenation xanthene and the derivant thereof of radiation sensitization; X-ray contrast agent; The medicament that contains radiation sensitization element; Iodate BrdU and bromination BrdU and related agents; Halogenation nucleic acid and DNA part and intercalator; Based on the acridine that replaces and the medicament of imidazoles; Nitroimidazole and relevant biological reductant; Misonidazole and related agents; Etanidazole and related agents; Pimondazole and relevant piperidine derivative; Aziridine and related agents; Cyclophosphamide and related agents; Nitroso ureas and related agents; L-phenylalanine mustard and related agents; Cis-Platinum compound and related agents; With amycin and related agents.
62. medicament as claim 61, wherein the halogenation xanthene is selected from halogenation xanthene and the highly iodinating halogenation xanthene and the derivant thereof of rose-red and derivant, phloxin B and derivant thereof, Erythrosin B and derivant, eosin W or W S and derivant thereof, height bromination, comprise 4,5,6,7-tetrabromo Erythrosin.
63. as the medicament of claim 61, wherein x-ray contrast agent is selected from Omnipaque
TM(iohexol), Omniscan
TM(gadodiamide), WIN8883 (diatrizoicacid), iodamide and ethiodized Oil.
64., wherein radiate the sensitization element and be selected from iodine, bromine, chlorine, barium, bismuth, boron, gold, silver, platinum, ferrum, gadolinium, dysprosium and tantalum as the medicament of claim 61.
65. as the medicament of claim 56, wherein the radioactive source component is selected from following radioactive component: aluminum, americium, cobalt, copper, gallium, gold, indium, iodine, iridium, manganese, phosphorus, radium, rhenium, rhodium, ruthenium, sulfur, technetium, thallium, yttrium and zinc.
66. method as claimed in claim 1 wherein realizes the distribution of radiosensitizer and the distribution of ionization radioactive source by while administration radiosensitizer and ionization radioactive source.
67. the method for a treated tissue designated volume, it comprises the following steps:
To patient's administration radiosensitizer, the part of this radiosensitizer almost spreads all in the tissue volume;
To or near a large amount of radioactive sources of tissue volume topical administration, this radioactive source spreads all over tissue volume, in tissue volume, produce basically radiation uniformly.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23624799A | 1999-01-25 | 1999-01-25 | |
| US09/236,247 | 1999-01-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1337886A true CN1337886A (en) | 2002-02-27 |
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| CN00803059A Pending CN1337886A (en) | 1999-01-25 | 2000-01-25 | Method for improved radiation therapy |
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| EP (1) | EP1146912A4 (en) |
| JP (1) | JP2002535291A (en) |
| KR (1) | KR20020001723A (en) |
| CN (1) | CN1337886A (en) |
| AR (1) | AR022404A1 (en) |
| AU (1) | AU2972500A (en) |
| BR (1) | BR0007692A (en) |
| CA (1) | CA2358989A1 (en) |
| IL (1) | IL144428A0 (en) |
| WO (1) | WO2000043045A1 (en) |
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|---|---|---|---|---|
| WO2000025829A2 (en) * | 1998-10-29 | 2000-05-11 | The General Hospital Corporation | Radiodense compositions |
| US20020001567A1 (en) * | 1998-12-21 | 2002-01-03 | Photogen, Inc. | Intracorporeal medicaments for high energy phototherapeutic treatment of disease |
| US8470296B2 (en) | 1998-12-21 | 2013-06-25 | Provectus Pharmatech, Inc. | Intracorporeal medicaments for high energy phototherapeutic treatment of disease |
| US6818227B1 (en) | 1999-02-08 | 2004-11-16 | Alza Corporation | Liposome composition and method for administration of a radiosensitizer |
| CN1205999C (en) * | 1999-02-08 | 2005-06-15 | 阿尔萨公司 | Liposome composition and method for administering radiosensitizer |
| AU6376100A (en) * | 1999-08-02 | 2001-02-19 | Regents Of The University Of Michigan, The | Targeted fiberless radiative effectors |
| AU2001297657A1 (en) * | 2000-11-16 | 2002-09-12 | Microspherix Llc | Polymeric imagable brachytherapy seed |
| US6746661B2 (en) | 2000-11-16 | 2004-06-08 | Microspherix Llc | Brachytherapy seed |
| US7776310B2 (en) | 2000-11-16 | 2010-08-17 | Microspherix Llc | Flexible and/or elastic brachytherapy seed or strand |
| MXPA06006683A (en) * | 2003-12-11 | 2006-08-11 | Schering Ag | Method to improve the efficacy of therateutic radiolabeled drugs. |
| WO2007008232A2 (en) | 2004-09-03 | 2007-01-18 | Board Of Regents, The University Of Texas System | Locoregional internal radionuclide ablation of abnormal tissues. |
| WO2006037081A2 (en) * | 2004-09-28 | 2006-04-06 | The Regents Of The University Of California | Nanoparticle radiosensitizers |
| WO2006138145A1 (en) | 2005-06-14 | 2006-12-28 | Northwestern University | Nucleic acid functionalized nanoparticles for therapeutic applications |
| WO2008098248A2 (en) | 2007-02-09 | 2008-08-14 | Northwestern University | Particles for detecting intracellular targets |
| DK2160464T3 (en) | 2007-05-30 | 2014-08-04 | Univ Northwestern | NUCLEIC ACID FUNCTIONALIZED NANOPARTICLES FOR THERAPEUTIC APPLICATIONS |
| KR101525132B1 (en) * | 2008-10-08 | 2015-06-02 | 포항공과대학교 산학협력단 | Capsule of x-ray contrast agent and preparing method thereof |
| KR101692880B1 (en) | 2008-11-24 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | Polyvalent rna-nanoparticle compositions |
| US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
| US8269197B2 (en) | 2009-07-22 | 2012-09-18 | Intraop Medical Corporation | Method and system for electron beam applications |
| WO2011017456A2 (en) * | 2009-08-04 | 2011-02-10 | Northwestern University | Localized delivery of nanoparticles for therapeutic and diagnostic applications |
| KR20120136345A (en) | 2009-10-30 | 2012-12-18 | 노오쓰웨스턴 유니버시티 | Templated nanoconjugates |
| US9393439B2 (en) | 2010-03-01 | 2016-07-19 | Intraop Medical Corporation | Radiotherapy combined with hypoxic cell sensitizers |
| JP2014526517A (en) | 2011-09-14 | 2014-10-06 | ノースウェスタン ユニバーシティ | Nanoconjugates that can cross the blood-brain barrier |
| CA2919268C (en) | 2013-07-25 | 2023-09-05 | Exicure, Inc. | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
| CA2968531A1 (en) | 2014-11-21 | 2016-05-26 | Northwestern University | The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| WO2016148969A1 (en) * | 2015-03-13 | 2016-09-22 | The Board Of Regents Of The University Of Texas System | Kub5/hera as a determinant of sensitivity to dna damage |
| US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
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|---|---|---|---|---|
| US4490543A (en) * | 1982-11-12 | 1984-12-25 | University Of Northern Iowa Foundation | Low toxicity radiation sensitizer |
| US5342283A (en) * | 1990-08-13 | 1994-08-30 | Good Roger R | Endocurietherapy |
| US5556992A (en) * | 1994-09-02 | 1996-09-17 | Universite De Montreal | Novel rhodamine derivatives for photodynamic therapy of cancer and in vitro purging of the leukemias |
| US6331286B1 (en) * | 1998-12-21 | 2001-12-18 | Photogen, Inc. | Methods for high energy phototherapeutics |
| US6015541A (en) * | 1997-11-03 | 2000-01-18 | Micro Therapeutics, Inc. | Radioactive embolizing compositions |
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2000
- 2000-01-24 AR ARP000100289A patent/AR022404A1/en unknown
- 2000-01-25 WO PCT/US2000/001815 patent/WO2000043045A1/en not_active Application Discontinuation
- 2000-01-25 CN CN00803059A patent/CN1337886A/en active Pending
- 2000-01-25 IL IL14442800A patent/IL144428A0/en unknown
- 2000-01-25 EP EP00908366A patent/EP1146912A4/en not_active Withdrawn
- 2000-01-25 CA CA002358989A patent/CA2358989A1/en not_active Abandoned
- 2000-01-25 BR BR0007692-9A patent/BR0007692A/en not_active Application Discontinuation
- 2000-01-25 JP JP2000594498A patent/JP2002535291A/en active Pending
- 2000-01-25 AU AU29725/00A patent/AU2972500A/en not_active Abandoned
- 2000-01-25 KR KR1020017009307A patent/KR20020001723A/en not_active Application Discontinuation
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| IL144428A0 (en) | 2002-05-23 |
| AR022404A1 (en) | 2002-09-04 |
| JP2002535291A (en) | 2002-10-22 |
| AU2972500A (en) | 2000-08-07 |
| KR20020001723A (en) | 2002-01-09 |
| CA2358989A1 (en) | 2000-07-27 |
| EP1146912A4 (en) | 2003-05-21 |
| WO2000043045A1 (en) | 2000-07-27 |
| EP1146912A1 (en) | 2001-10-24 |
| BR0007692A (en) | 2001-11-06 |
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