Photocurable composition and method for delivering radiation to a subject

Abstract

The present disclosure relates, in part, to a polymerizable biocompatible or bioabsorbable composition comprising monomers of styrene, N-vinylpyrrolidone or acrylate, further comprising oligomers of epoxide, urethane, polyether or polyester, and a free radical initiator, and capable of incorporating a radiation source comprising a diagnostic or therapeutic radioisotope and a radioisotope precursor, to a composition for treating a subject having a particular condition, and to a method of manufacturing the same and its use.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority based on U.S. Provisional Application No. 63 / 352,714, filed on June 16, 2022, the entire content of which is incorporated herein by reference.

[0002] The present embodiment generally relates to a polymerizable composition that can incorporate a radiation source and is used to treat a subject having a specific condition. The present embodiment also relates to a method of forming a three - dimensionally printed article incorporating a radioactive material adapted to the area to be treated.

Background Art

[0003] Radioactive substances or seeds are often used to treat various conditions, including skin conditions such as various types of skin cancer. Heretofore, it has been difficult to apply a radiation - source material to a specific area without irradiating healthy tissue. Therefore, there is a need for a polymerizable material that can incorporate a radioactive substance and is manufactured by a method adapted to the area to be treated. The present embodiment satisfies these and other needs.

Summary of the Invention

Problems to be Solved by the Invention

[0004] In part, the present disclosure provides a curable composition comprising a first composition comprising one or more monomers, a second composition comprising one or more oligomers, a third composition capable of creating free radicals when exposed to radiation (e.g., ultraviolet light, infrared light, etc.); and a fourth composition comprising one or more radioisotopes.

Means for Solving the Problems

[0005] In some embodiments, the first composition comprises styrene, N - vinylpyrrolidone, acrylate, or a mixture thereof.

[0006] In some embodiments, the second composition comprises an epoxide, a urethane, a polyether, a polyester, or any combination thereof.

[0007] In some embodiments, the composition comprising one or more radioisotopes is in the form of a solution, a colloid, microspheres, or nanoparticles.

[0008] In some embodiments, the isotope or isotopes are Pd-103, Pd-109, I-125, I-124, I-123, I-131, P-32, Y-90, Ac-225, Cs-131, B-10, Ir-192, Sn-177m, Ho-166, Cu-64, Cu-67, Re-186, Re-188, Ga-67, Ga-68, In-111, Co-60, Cs-137, Lu-177, Yb-169, Er-169, Au-198, Sm-153, Am-241, Sr-89, Ra-223, Pb-212, Bi-213, Tc-99, At-211, Cf-252, or any combination thereof.

[0009] In some embodiments, styrene is 3-vinylphenylboronic acid, 1-vinylnaphthalene, 4-vinylbenzylamine, vinyltoluene monomer, 2,2'-(2-vinylanthracene-9,10-diylidene)bis(1,3-dithiol), 4-tert-butylstyrene, 2,3,4,5,6-pentafluorostyrene, 3-aminostyrene, 3-bromostyrene, 2-vinylanthraquinone, 4-fluoro-α-methylstyrene, 4-chlorostyrene, 2-chlorostyrene, chloromethylstyrene, 9-vinylanthracene, sodium p-styrenesulfonate hydrate, 4-methoxystyrene, 2-bromostyrene, 4-bromo-β,β-difluorostyrene, 3-fluorostyrene, 4-n-octylstyrene, 2,2'-(2-vinylanthracene-9,10-diylidene)dimalononitrile, divinylbenzene, 4-(chloromethyl)styrene, 2-vinylphenyl acetate, 3-chlorostyrene, vinylbenzyl cyanide, 3-(trifluoromethyl)styrene, 2,4,6-trimethylstyrene, trimethoxy(4-vinylphenyl)silane, 2-methylstyrene, 4-methylstyrene, 4-vinylbiphenyl, 4-isopropenyltoluene, 4-tert-butoxystyrene, 1-(1-ethoxyethoxy)-4-vinylbenzene, trimethyl(4-vinylphenyl)silane, 4-vinylphenyl acetate, α-methylstyrene, styrene, 4-aminostyrene, 4-fluorostyrene, 4-(trifluoromethyl)styrene, diphenyl(4-vinylphenyl)phosphine, 4-vinylbenzoic acid, 4-vinylphenylboronic acid, 4-nitrostyrene, 4-bromostyrene, 3-methylstyrene, or any combination thereof.

[0010] In some embodiments, the isotope is Pd-103.

[0011] In some embodiments, the Pd-103 isotope is produced from Pd-102 or Pd-104.

[0012] In some embodiments, the isotope is Y-90.

[0013] In some embodiments, the isotope is Sn-177m.

[0014] In some embodiments, a method for preparing a substantially cured composition is provided. In some embodiments, the method includes mixing a curable composition, such as those provided herein, with a photoinitiator to form a substantially cured composition.

[0015] In some embodiments, a method for preparing a substantially cured composition is provided. In some embodiments, the method includes mixing a curable composition, such as those provided herein, printing the composition in a three-dimensional structure of a target area with a 3-D printer, and curing the composition using a photoinitiator to form a substantially cured composition in the shape of the three-dimensional structure of the target area.

[0016] In some embodiments, a method for treating a subject using radiation is provided. In some embodiments, the method includes applying, implanting, contacting, etc., a cured composition prepared from any one of those provided herein.

DETAILED DESCRIPTION OF THE INVENTION

[0017] A, An, The: As used herein, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0018] About, Approximately: As used herein, the terms "about" and "approximately" are generally intended to mean an acceptable degree of error for the measured quantity considering the nature or precision of the measurement. Exemplary degrees of error are within 15 percent (%), typically within 10%, more typically within 5% of a given value or range of values.

[0019] A "polymer" is a substance composed of macromolecules. Polymer macromolecules are molecules with a high relative molecular weight, and their structure includes multiple repeating units derived from molecules with a low relative molecular weight.

[0020] A "branched polymer" is a polymer that includes side chains of repeating units (different from the side chains already present in the monomer) that are linked to the main chain of repeating units. A branched polymer refers to a non-linear polymer structure, but typically is not a network structure. Thus, there are no cross-links that return to the original main chain when traced forward from the branch point; that is, the cross-linked backbone is minimal or non-existent. Branched polymers are generally soluble in suitable solvents.

[0021] A "cross-linked polymer" is a polymer that includes inter-chain cross-links formed either during polymerization (by selection of monomers) or after polymerization (by addition of specific reagents). In a cross-linked polymer network, it is possible to trace continuous loops back to the backbone by cross-links that act as branch points. Cross-linked networks are insoluble in all solvents.

[0022] A "network polymer" is a cross-linked polymer that includes on average two or more linkages between chains, and the entire sample is, or potentially is, a single molecule. Limited cross-linking connections per chain are considered lightly cross-linked, while numerous cross-links are considered highly (or severely) cross-linked.

[0023] A "copolymer" is a substance created by polymerizing a mixture of two or more starting compounds. The resulting polymer molecules contain monomers in ratios related to both the molar fractions of the monomers in the starting mixture and the reaction mechanism.

[0024] As used herein, the terms "subject", "individual", or "patient" are used interchangeably and mean any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, or primates such as humans.

[0025] As used herein, the phrase "in need thereof" means that an animal or mammal is identified as having a need for a particular method or treatment. In some embodiments, the identification can be by any diagnostic means. In any of the methods and treatments described herein, an animal or mammal may be in need thereof. In some embodiments, the animal or mammal is in or moves to an environment where a particular disease, disorder or condition is prevalent. For example, in some embodiments, the subject is a subject in need of radiation treatment due to a condition such as skin cancer.

[0026] As used herein, the phrase "an integer from X to Y" means any integer including the endpoints. For example, the phrase "an integer from 1 to 5" means 1, 2, 3, 4 or 5.

[0027] As used herein, the term "mammal" means a rodent (i.e., mouse, rat or guinea pig), monkey, cat, dog, cow, horse, pig, or human. In some embodiments, the mammal is a human.

[0028] As used herein, the phrase "therapeutically effective amount" means the amount of an active compound, radioisotope or pharmaceutical formulation that elicits a biological or medical response being investigated by a researcher, veterinarian, physician or other clinician in a tissue, system, animal, individual or human. The therapeutic effect depends on the disorder or desired biological effect being treated. Thus, the therapeutic effect can be a decrease in the severity of symptoms associated with the disorder, and / or inhibition (partial or complete) of the progression of the disorder, or an improvement in the treatment, cure, elimination of the disorder or side effects. The amount required to elicit a therapeutic response can be determined based on the age, health status, build and gender of the subject. The optimal amount can also be determined based on observation of the subject's response to the treatment.

[0029] As used herein, the terms "treating," "being treated," or "treatment" mean both therapeutic treatment and prophylactic measures, the purpose of which is to alleviate (reduce) a undesired physiological condition, disorder or disease, or to obtain a beneficial or desired clinical outcome. Beneficial or desired clinical outcomes include, but are not limited to, alleviation of symptoms; reduction in the degree of a condition, disorder or disease; a stabilized (i.e., not worsening) condition, disorder or disease; delay in onset or slowing of progression of a condition, disorder or disease; amelioration or remission (partial or total) of a condition, disorder or disease state, whether detectable or undetectable; amelioration of at least one measurable physical parameter not necessarily recognized by a patient; or enhancement or improvement of a condition, disorder or disease. Treatment includes inducing a clinically significant response without undue levels of side effects, such as avoiding significant exposure of healthy tissue to radiation. Treatment also includes extending the survival period as compared to the expected survival period if not receiving treatment.

[0030] As used herein, the term "contacting" means bringing two elements together in an in vitro or in vivo system, such as applying or adhering a composition provided herein to the skin of a subject, or implanting a composition into a cavity, organ, tissue, etc. within a subject.

[0031] As used herein, the term "comprising" (and any form of comprising, such as "comprise", "comprises", and "comprised"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include"), or "containing" (and any form of containing, such as "contains" and "contain") is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.

[0032] As used herein, the term "cancer" refers to the onset or progression of a malignant tumor, as well as a wide range of pathological symptoms associated with metastasis. Examples include, but are not limited to, skin cancer. Examples of skin cancer include, but are not limited to, malignant melanoma (MM), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC).

[0033] As used herein, the term "animal" includes, but is not limited to, humans and non-human vertebrates such as wild, captive, and domestic animals.

[0034] As used herein, the term "about" means that a numerical value is an approximation and that minor variations do not significantly affect the implementation of the embodiments of the present disclosure. When numerical limitations are used, unless otherwise indicated by the context, "about" means that the numerical value may vary by up to 10% and still remain within the scope of the embodiments of the present disclosure. In some embodiments, the numerical value may vary by up to 5% and still remain within the scope of the embodiments of the present disclosure.

[0035] In some embodiments, a curable composition is provided that can be used, for example, to treat a condition in a subject that requires radiation to be delivered to a specific tissue or other region on or within the subject. The composition can be a polymer composition formed from a combination of polymers, network polymers, cross-linked polymers, copolymers, branched polymers, and the like.

[0036] In some embodiments, the curable composition includes a first composition comprising one or more monomers, a second composition comprising one or more oligomers, a third composition capable of creating free radicals; and a fourth composition comprising one or more radioisotopes. Without being bound by theory, the third composition promotes the polymerization and curing of the first and second compositions when free radicals are generated. Free radicals can be generated via any known method, and thus, the third composition can include any such components necessary for the generation of free radicals. In some embodiments, the free radicals are generated through a chemical reaction occurring within the third composition. In some embodiments, the free radicals are generated when the third composition is exposed to radiation. The radiation can be ultraviolet light, infrared light, thermal radiation, or any other form of radiation used to promote the curing / polymerization of the composition. In some embodiments, the radiation is ultraviolet light. In some embodiments, the radiation is infrared light. In some embodiments, the radiation is thermal radiation.

[0037] In some embodiments, the composition comprises a therapeutically effective amount of a radioisotope. In some embodiments, the radioisotope is present in an amount sufficient to be detected and located. Detection and location can be by any means known in the art. By way of non-limiting example, the radioisotope can be detected with a portable frisker or Geiger counter, and thus the radioisotope is located by reading the frisker or Geiger counter. As another non-limiting example, the radioisotope can be detected by an image processing processor and located by the image processing processor. Thus, in some embodiments, the radioisotope is present in an amount sufficient to be detected and located by a portable frisker such as a Geiger counter. In some embodiments, the radioisotope is present in an amount sufficient to be detected and located by an image processing processor. In some embodiments, the radioisotope is present in an amount sufficient to deliver a therapeutic dose of radiation to a mammal.

[0038] In some embodiments, one or more radioisotopes are therapeutic radioisotopes, diagnostic radioisotopes, or combinations thereof. As used herein, "therapeutic radioisotope" is any radioisotope used to deliver a therapeutic radiation to a subject in need thereof for the treatment of a disease or disorder. As used herein, "diagnostic radioisotope" is any radioisotope used in combination with an imaging unit and an image processing processor to assist in the diagnosis of any disease or disorder. It should be understood that "therapeutic radioisotope" and "diagnostic radioisotope" are not mutually exclusive.

[0039] In some embodiments, one or more radioisotopes include diagnostic radioisotopes. In some embodiments, the diagnostic radioisotopes are present in an amount sufficient to be detected and located. Detection and location can be by any means known in the art. By way of non-limiting example, the radioisotope can be detected with a portable frisker or Geiger counter, and thus the radioisotope is located by reading the frisker or Geiger counter. As another non-limiting example, the radioisotope can be detected by an image processing processor and located by the image processing processor. Thus, in some embodiments, the radioisotope is present in an amount sufficient to be detected and located by a portable frisker such as a Geiger counter. In some embodiments, the radioisotope is present in an amount sufficient to be detected and located by an image processing processor. In some embodiments, the diagnostic radioisotopes are produced from one or more radioisotope precursors. In some embodiments, the radioisotope precursors are present in an amount sufficient to produce an amount of diagnostic radioisotope sufficient to be detected and located as provided herein.

[0040] In some embodiments, one or more radioisotopes include therapeutic radioisotopes. In some embodiments, the therapeutic radioisotopes are present in an amount sufficient to deliver a therapeutic dose of radiation to a mammal. In some embodiments, the therapeutic radioisotopes are produced from one or more radioisotope precursors. In some embodiments, the radioisotope precursors are present in an amount sufficient to produce an amount of therapeutic radioisotope sufficient to deliver a therapeutic dose of radiation to a mammal.

[0041] In some embodiments, one or more radioisotopes are uniformly distributed throughout the curable composition. In some embodiments, one or more radioisotopes are not uniformly distributed throughout the curable composition. Without being bound by any particular theory, the radioisotopes of the present disclosure can be spatially distributed throughout the curable composition such that some portion or portions of the composition contain a higher in-region concentration of radioisotope than other regions of the composition. Such compositions are useful, for example, for performing dosimetry of radiation matched to a particular treatment region.

[0042] In some embodiments, the curable composition is biocompatible. As used herein, the term "biocompatible" refers to a composition that can be used on a subject, such as a human or animal, without causing significant side effects or adverse effects to the composition.

[0043] In some embodiments, the curable composition is bioabsorbable. A "bioabsorbable" composition is a composition that is absorbed or degraded over time.

[0044] In some embodiments, one or more monomers of the first composition include styrene, N-vinylpyrrolidone, acrylate, or a mixture thereof. In some embodiments, one or more monomers of the first composition include styrene. In some embodiments, one or more monomers of the first composition include N-vinylpyrrolidone. In some embodiments, one or more monomers of the first composition include acrylate. In some embodiments, one or more monomers of the first composition include a combination of styrene and N-vinylpyrrolidone. In some embodiments, one or more monomers of the first composition include a combination of styrene and acrylate. In some embodiments, one or more monomers of the first composition include a combination of N-vinylpyrrolidone and acrylate. In some embodiments, one or more monomers of the first composition include a combination of styrene, N-vinylpyrrolidone, and acrylate.

[0045] The styrene of the first composition can be any suitable styrene known in the art. Examples of "styrene" include 3-vinylphenylboronic acid, 1-vinylnaphthalene, 4-vinylbenzylamine, vinyltoluene monomer, 2,2'-(2-vinylanthracene-9,10-diylidene)bis(1,3-dithiol), 4-tert-butylstyrene, 2,3,4,5,6-pentafluorostyrene, 3-aminostyrene, 3-bromostyrene, 2-vinylanthraquinone, 4-fluoro-α-methylstyrene, 4-chlorostyrene, 2-chlorostyrene, chloromethylstyrene, 9-vinylanthracene, sodium p-styrenesulfonate hydrate, 4-methoxystyrene, 2-bromostyrene, 4-bromo-β,β-difluorostyrene, 3-fluorostyrene, 4-n-octylstyrene, 2,2'-(2-vinylanthracene-9,10-diylidene)dimalononitrile, divinylbenzene, 4-(chloromethyl)styrene, 2-vinylphenyl acetate, 3-chlorostyrene, vinylbenzyl cyanide, 3-(trifluoromethyl)styrene, 2,4,6-trimethylstyrene, trimethoxy(4-vinylphenyl)silane, 2-methylstyrene, 4-methylstyrene, 4-vinylbiphenyl, 4-isopropenyltoluene, 4-tert-butoxystyrene, 1-(1-ethoxyethoxy)-4-vinylbenzene, trimethyl(4-vinylphenyl)silane, 4-vinylphenyl acetate, α-methylstyrene, styrene, 4-aminostyrene, 4-fluorostyrene, 4-(trifluoromethyl)styrene, diphenyl(4-vinylphenyl)phosphine, 4-vinylbenzoic acid, 4-vinylphenylboronic acid, 4-nitrostyrene, 4-bromostyrene, 3-methylstyrene, or any combination thereof, including but not limited to these. In some embodiments, the styrene is 3-vinylphenylboronic acid. In some embodiments, the styrene is 1-vinylnaphthalene. In some embodiments, the styrene is 4-vinylbenzylamine. In some embodiments, the styrene is vinyltoluene monomer. In some embodiments, the styrene is 2,2'-(2-vinylanthracene-9,10-diylidene)bis(1,3-dithiol).In some embodiments, the styrene is 4-tert-butylstyrene, 2,3,4,5,6-pentafluorostyrene. In some embodiments, the styrene is 3-aminostyrene. In some embodiments, the styrene is 3-bromostyrene. In some embodiments, the styrene is 2-vinylanthraquinone. In some embodiments, the styrene is 4-fluoro-α-methylstyrene. In some embodiments, the styrene is 4-chlorostyrene. In some embodiments, the styrene is 2-chlorostyrene. In some embodiments, the styrene is chloromethylstyrene. In some embodiments, the styrene is 9-vinylanthracene. In some embodiments, the styrene is sodium p-styrenesulfonate hydrate. In some embodiments, the styrene is 4-methoxystyrene. In some embodiments, the styrene is 2-bromostyrene. In some embodiments, the styrene is 4-bromo-β,β-difluorostyrene. In some embodiments, the styrene is 3-fluorostyrene. In some embodiments, the styrene is 4-n-octylstyrene. In some embodiments, the styrene is 2,2'-(2-vinylanthracene-9,10-diylidene)dimalononitrile. In some embodiments, the styrene is divinylbenzene. In some embodiments, the styrene is 4-(chloromethyl)styrene. In some embodiments, the styrene is 2-vinylphenyl acetate. In some embodiments, the styrene is 3-chlorostyrene. In some embodiments, the styrene is vinylbenzyl cyanide. In some embodiments, the styrene is 3-(trifluoromethyl)styrene. In some embodiments, the styrene is 2,4,6-trimethylstyrene. In some embodiments, the styrene is trimethoxy(4-vinylphenyl)silane. In some embodiments, the styrene is 2-methylstyrene. In some embodiments, the styrene is 4-methylstyrene. In some embodiments, the styrene is 4-vinylbiphenyl. In some embodiments, the styrene is 4-isopropenyltoluene. In some embodiments, the styrene is 4-tert-butoxystyrene. In some embodiments, the styrene is 1-(1-ethoxyethoxy)-4-vinylbenzene.In some embodiments, styrene is trimethyl(4-vinylphenyl)silane. In some embodiments, styrene is 4-vinylphenyl acetate. In some embodiments, styrene is α-methylstyrene. In some embodiments, styrene is styrene. In some embodiments, styrene is 4-aminostyrene. In some embodiments, styrene is 4-fluorostyrene. In some embodiments, styrene is 4-(trifluoromethyl)styrene. In some embodiments, styrene is diphenyl(4-vinylphenyl)phosphine. In some embodiments, styrene is 4-vinylbenzoic acid. In some embodiments, styrene is 4-vinylphenylboronic acid. In some embodiments, styrene is 4-nitrostyrene. In some embodiments, styrene is 4-bromostyrene. In some embodiments, styrene is 3-methylstyrene. In some embodiments, styrene is any combination of the above.

[0046] The acrylate of the first composition can be any suitable acrylate known in the art. Examples of acrylates that can be used include, but are not limited to, t-butyl acrylate, t-butyl acrylamide, n-octyl methacrylate, methyl methacrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, their derivatives, and combinations thereof. In some embodiments, the acrylate is t-butyl acrylate, or a derivative thereof. In some embodiments, the acrylate is t-butyl acrylamide, or a derivative thereof. In some embodiments, the acrylate is n-octyl methacrylate, or a derivative thereof. In some embodiments, the acrylate is methyl methacrylate, or a derivative thereof. In some embodiments, the acrylate is hydroxyethyl methacrylate, or a derivative thereof. In some embodiments, the acrylate is hydroxyethyl acrylate, or a derivative thereof. In some embodiments, the acrylate is hydroxypropyl methacrylate, or a derivative thereof. In some embodiments, the acrylate is hydroxybutyl methacrylate, or a derivative thereof. In some embodiments, the acrylate is any combination of the above. In some embodiments, the acrylate is hydroxyethyl methacrylate (HEMA).

[0047] In some embodiments, the oligomers of the second composition include epoxides (epoxide-containing compounds), urethanes, polyethers, polyesters, or any combination thereof. In some embodiments, the oligomers of the second composition include epoxides (epoxide-containing compounds). In some embodiments, the oligomers of the second composition include urethanes. In some embodiments, the oligomers of the second composition include polyethers. In some embodiments, the oligomers of the second composition include polyesters. In some embodiments, the oligomers of the second composition include a combination of epoxide and urethane. In some embodiments, the oligomers of the second composition include a combination of epoxide and polyether. In some embodiments, the oligomers of the second composition include a combination of epoxide and polyester. In some embodiments, the oligomers of the second composition include a combination of urethane and polyether. In some embodiments, the oligomers of the second composition include a combination of urethane and polyester. In some embodiments, the oligomers of the second composition include a combination of epoxide, urethane, and polyether. In some embodiments, the oligomers of the second composition include a combination of epoxide, urethane, and polyester. In some embodiments, the oligomers of the second composition include a combination of epoxide, polyether, and polyester. In some embodiments, the oligomers of the second composition include a combination of epoxide, urethane, polyether, and polyester.

[0048] The terms "epoxide" and "epoxy group" refer to a chemical functional group consisting of a three-membered ring arrangement of two carbon atoms and one oxygen atom. The two carbon atoms in the three-membered ring may be independently substituted. The term "epoxide" may also represent a molecule or compound containing at least one epoxy group. The term "epoxide-containing compound" refers to any compound that is a compound containing an epoxide or an epoxide moiety. Non-limiting examples of epoxide-containing compounds include alkylene oxides such as lower alkylene oxides like ethylene oxide, propylene oxide, butylene oxide, alcohol epoxides such as glycidol, and epihalohydrins such as epichlorohydrin, epibromohydrin, epi-iodohydrin, 1,2-epoxy-4-chlorobutane, 1,2-epoxy-4-bromobutane, 1,2-epoxy-4-iodobutane, 2,3-epoxy-4-chlorobutane, 2,3-epoxy-4-bromobutane, 2,3-epoxy-4-iodobutane, 2,3-epoxy-5-chloropentane, 2,3-epoxy-5-bromopentane, 1,2-epoxy-5-chloropentane, epoxy compounds such as 2,2-bis(p-1,2-epoxypropoxyphenyl)-propane, 1,4-bis(1,2-epoxypropoxy)benzene, N,N'-bis(2,3-epoxypropyl)piperazine. In some embodiments, the epoxide-containing compound is an alkylene oxide. In some embodiments, the epoxide-containing compound is an alkylene oxide. In some embodiments, the epoxide-containing compound is ethylene oxide. In some embodiments, the epoxide-containing compound is propylene oxide. In some embodiments, the epoxide-containing compound is butylene oxide. In some embodiments, the epoxide-containing compound is an alcohol epoxide. In some embodiments, the epoxide-containing compound is glycidol. In some embodiments, the epoxide-containing compound is an epihalohydrin. In some embodiments, the epoxide-containing compound is epichlorohydrin. In some embodiments, the epoxide-containing compound is epibromohydrin. In some embodiments, the epoxide-containing compound is epi-iodohydrin. In some embodiments, the epoxide-containing compound is 1,2-epoxy-4-chlorobutane.In some embodiments, the epoxide-containing compound is 1,2-epoxy-4-bromobutane. In some embodiments, the epoxide-containing compound is 1,2-epoxy-4-iodobutane. In some embodiments, the epoxide-containing compound is 2,3-epoxy-4-chlorobutane. In some embodiments, the epoxide-containing compound is 2,3-epoxy-4-bromobutane. In some embodiments, the epoxide-containing compound is 2,3-epoxy-4-iodobutane. In some embodiments, the epoxide-containing compound is 2,3-epoxy-5-chloropentane. In some embodiments, the epoxide-containing compound is 2,3-epoxy-5-bromopentane. In some embodiments, the epoxide-containing compound is 1,2-epoxy-5-chloropentane. In some embodiments, the epoxide-containing compound is 2,2-bis(p-1,2-epoxypropoxyphenyl)-propane. In some embodiments, the epoxide-containing compound is 1,4-bis(1,2-epoxypropoxy)benzene. In some embodiments, the epoxide-containing compound is N,N'-bis(2,3-epoxypropyl)piperazine. In some embodiments, the epoxide-containing compound is any combination of the above.

[0049] In some embodiments, the urethane is any suitable urethane. In some embodiments, the urethane is a polyurethane oligomer.

[0050] In some embodiments, the polyether is any suitable polyether. In some embodiments, the polyether is polyethylene oxide or polypropylene oxide. In some embodiments, the polyether is polyethylene oxide. In some embodiments, the polyether is polypropylene oxide.

[0051] In some embodiments, the polyester is any suitable polyester. In some embodiments, the polyester is polylactic acid (PLA), polyglycolic acid, PGA, or a copolymer of polylactic acid and polyglycolic acid (PLGA). In some embodiments, the polyester is PLA. In some embodiments, the polyester is PGA. In some embodiments, the polyester is PLGA.

[0052] The composition comprising one or more radioisotopes can be in any form such as, but not limited to, a solution, a colloid, microspheres, or nanoparticles. In some embodiments, the fourth composition comprising one or more radioisotopes can be in any form such as, but not limited to, a solution, a colloid, microspheres, or nanoparticles. In some embodiments, the fourth composition is in the form of a solution. In some embodiments, the fourth composition is in the form of a colloid. In some embodiments, the fourth composition is in the form of microspheres. In some embodiments, the fourth composition is in the form of nanoparticles.

[0053] In some embodiments, one or more radioisotopes include Pd-103, I-125, P-32, Y-90, Ac-225, Cs-131, B-10, Ir-192, Sn-177m, Ho-166, Pd-109, Cu-64, Cu-67, Re-186, Re-188, Ga-67, Ga-68, In-111, Co-60, Cs-137, Lu-177, Yb-169, Er-169, Au-198, Sm-153, Am-241, Sr-89, Ra-223, Pb-212, Bi-213, Tc-99, At-211, Cf-252, or any combination thereof. In some embodiments, the radioisotope is Pd-103. In some embodiments, the radioisotope is I-125. In some embodiments, the radioisotope is P-32. In some embodiments, the radioisotope is Y-90. In some embodiments, the radioisotope is Ac-225. In some embodiments, the radioisotope is Cs-131. In some embodiments, the radioisotope is B-10. In some embodiments, the radioisotope is Ir-192. In some embodiments, the radioisotope is Sn-177m. In some embodiments, the radioisotope is Ho-166. In some embodiments, the radioisotope is Pd-109. In some embodiments, the radioisotope is Cu-64. In some embodiments, the radioisotope is Cu-67. In some embodiments, the radioisotope is Re-186. In some embodiments, the radioisotope is Re-188. In some embodiments, the radioisotope is Ga-67. In some embodiments, the radioisotope is Ga-68. In some embodiments, the radioisotope is In-111. In some embodiments, the radioisotope is Co-60. In some embodiments, the radioisotope is Cs-137. In some embodiments, the radioisotope is Lu-177. In some embodiments, the radioisotope is Yb-169. In some embodiments, the radioisotope is Er-169. In some embodiments, the radioisotope is Au-198. In some embodiments, the radioisotope is Sm-153. In some embodiments, the radioisotope is Am-241. In some embodiments, the radioisotope is Sr-89.In some embodiments, the radioisotope is Ra-223. In some embodiments, the radioisotope is Rb-212. In some embodiments, the radioisotope is Bi-213. In some embodiments, the radioisotope is Tc-99. In some embodiments, the radioisotope is At-211. In some embodiments, the radioisotope is Cf-252. In some embodiments, the fourth composition comprises a combination of radioisotopes, and the radioisotope is selected from any of the above. In some embodiments, the radioisotope is Pd-103. In some embodiments, Pd-103 is produced from Pd-102 or Pd-104. In some embodiments, the radioisotope is Y-90. In some embodiments, Y-90 is produced from Y-89 or Sr-90.

[0054] In some embodiments, one or more radioisotopes in the fourth composition are produced by activating one or more radioisotope precursors. As used herein, "activating" one or more radioisotope precursors or their "activation" refers to any process or method known in the art for producing a desired radioisotope from a given radioisotope precursor. For example, activation of a radioisotope precursor can include bombarding (exposing) the precursor with high energy particles. The particles that bombard can include, but are not limited to, alpha particles (α), neutrons (n), 3 He atoms, protons (p), tritons (t), gamma rays (γ), heavy ions, and deuterons (d). Typical sources of these types of bombardment are nuclear reactors and particle accelerators. Examples of precursor activation are: using a (p,n) reaction to 103 produce Pd: 103 Rh(p,n)→ 103 Pd, where "p" is proton incidence and "n" is neutron emission; using a (n,γ) reaction to 103 produce Pd: 102 Pd(n,γ)→ 103 Pd, where "n" is neutron incidence and "γ" is gamma ray emission; using a (p,2n) reaction to103 Generating Pd: 104 Pd(p,2n)→ 103 Ag(ε)→ 103 Pd, where "p" is proton incidence, "2n" is the emission of two neutrons, and "ε" is electron capture; using the (n,γ) reaction to 32 Generating P: 31 P(n,γ)→ 32 P, where "n" is neutron incidence and "γ" is gamma ray emission; using the (n,α) reaction to 7 Generating Li and α: 10 B(n,α)→ 7 Li, where "n" is neutron incidence and "α" is alpha emission; or using the (n,γ) reaction to 90 Generating Y: 89 Y(n,γ)→ 90 Y, where "n" is neutron incidence and "γ" is gamma ray emission, including but not limited to these. Additional reactions for precursor activation are (α,3n), (α,2n), (α,n), (p,γ), (d,n), ( 3 He,np), (α,np), (t,n), ( 3 He,p), (p,pn), (γ,n), (n,2n), (d,p), (t,np), (t,p), (p,α), (n,t), (γ,np), (n,nd), (n,d), (γ,p), (n,np), (n,p), (t, 3 He), (n,α), (n,n 3 He), (n, 3Including, but not limited to, (He), (p,3n), (p,4n), and (n,pd). In some embodiments, this is utilized by activating a precursor in the cured composition. For example, in some embodiments, the isotope-modified precursor is incorporated into a curable device and then cured. The cured device is then exposed to a sufficient flux of neutron radiation for a period sufficient to activate the precursor to a predetermined activity level. This activity can be determined to be sufficient for the purpose. In some embodiments, the activated device can then be applied to a patient to deliver a therapeutic dose of radioactive material to the area designed to be treated. In some embodiments, another isotope-modified precursor can be used and the same or a similar process can be used, but instead of neutron radiation, the device is exposed to a proton beam of sufficient energy and flux to activate the precursor to a predetermined activity level and is then used to treat a patient as described herein.

[0055] A radioisotope precursor can be any precursor that is necessary or useful for generating a radioisotope as provided herein. Non-limiting examples of radioisotope precursors include, but are not limited to, Xe-124, S-32, Y-89, Sr-90, Th-229, Ir-191, Ir-193, Dy-164, Pd-102, Pd-104, Pd-108, B-10, P-31, Ni-64, Zn-67, Zn-68, Zn-70, Rh-103, Te-125, Te-124, Ba-130, Cs-133, Th-232, Sr-86, Er-168, Cd-111, Cd-112, W-186, Bi-209, Tm-169, Yb-176, Ra-226, or any combination thereof. In some embodiments, the radioisotope precursor is Xe-124. In some embodiments, the radioisotope precursor is S-32. In some embodiments, the radioisotope precursor is Y-89. In some embodiments, the radioisotope precursor is Sr-90. In some embodiments, the radioisotope precursor is Th-229. In some embodiments, the radioisotope precursor is Ir-191. In some embodiments, the radioisotope precursor is Ir-193. In some embodiments, the radioisotope precursor is Dy-164. In some embodiments, the radioisotope precursor is Pd-102. In some embodiments, the radioisotope precursor is Pd-104. In some embodiments, the radioisotope precursor is Pd-108. In some embodiments, the radioisotope precursor is B-10. In some embodiments, the radioisotope precursor is P-31. In some embodiments, the radioisotope precursor is Ni-64. In some embodiments, the radioisotope precursor is Zn-67. In some embodiments, the radioisotope precursor is Zn-68. In some embodiments, the radioisotope precursor is Zn-70. In some embodiments, the radioisotope precursor is Rh-103. In some embodiments, the radioisotope precursor is Te-125. In some embodiments, the radioisotope precursor is Te-124. In some embodiments, the radioisotope precursor is Th-232. In some embodiments, the radioisotope precursor is Sr-86.In some embodiments, the radioisotope precursor is Er-168. In some embodiments, the radioisotope precursor is Cd-111. In some embodiments, the radioisotope precursor is Cd-112. In some embodiments, the radioisotope precursor is W-186. In some embodiments, the radioisotope precursor is Bi-209. In some embodiments, the radioisotope precursor is Tm-169. In some embodiments, the radioisotope precursor is Yb-176. In some embodiments, the radioisotope precursor is Ra-226. In some embodiments, the fourth composition comprises a combination of radioisotope precursors, and the radioisotope precursor is selected from any of the above. In some embodiments, the radioisotope precursor is Pd-102 and the resulting radioisotope is Pd-103. In some embodiments, the radioisotope precursor is Pd-104 and the resulting radioisotope is Pd-103. In some embodiments, the radioisotope precursor is Rh-103 and the resulting radioisotope is Pd-103. In some embodiments, the radioisotope precursor is Pd-108 and the resulting radioisotope is Pd-109. In some embodiments, the radioisotope precursor is Xe-124 and the resulting radioisotope is I-125. In some embodiments, the radioisotope precursor is S-32 and the resulting radioisotope is P-32. In some embodiments, the radioisotope precursor is P-31 and the resulting radioisotope is P-32. In some embodiments, the radioisotope precursor is Y-89 and the resulting radioisotope is Y-90. In some embodiments, the radioisotope precursor is Sr-90 and the resulting radioisotope is Y-90. In some embodiments, the radioisotope precursor is Th-229 and the resulting radioisotope is Ac-225. In some embodiments, the radioisotope precursor is Ba-130 and the resulting radioisotope is Cs-131. In some embodiments, the radioisotope precursor is Ir-191 and the resulting radioisotope is Ir-192. In some embodiments, the radioisotope precursor is Ir-193 and the resulting radioisotope is Ir-192.In some embodiments, the radioisotope precursor is Dy-164 and the resulting radioisotope is Ho-166. In some embodiments, the radioisotope precursor is Ni-64 and the resulting radioisotope is Cu-64. In some embodiments, the radioisotope precursor is Zn-67 and the resulting radioisotope is Cu-67. In some embodiments, the radioisotope precursor is Zn-68 and the resulting radioisotope is Cu-67. In some embodiments, the radioisotope precursor is Zn-70 and the resulting radioisotope is Cu-67. In some embodiments, the radioisotope precursor is Cd-111 and the resulting radioisotope is In-111. In some embodiments, the radioisotope precursor is Cd-112 and the resulting radioisotope is In-111. In some embodiments, the radioisotope precursor is Tm-169 and the resulting radioisotope is Yb-169. In some embodiments, the radioisotope precursor is Tb-176 and the resulting radioisotope is Lu-177. In some embodiments, the radioisotope precursor is Ra-226 and the resulting radioisotope is Pb-212. It should be understood that the above embodiments are merely illustrative and in no way limiting. Those skilled in the art can readily recognize alternative radioisotope precursors capable of producing radioisotopes as provided herein. Similarly, those skilled in the art can readily recognize alternative radioisotopes produced from the radioisotope precursors provided herein. Such alternative radioisotope precursors and alternative radioisotopes are within the scope of the present disclosure.

[0056] A radioisotope or radioisotope precursor as provided herein can be in any suitable form for inclusion in a fourth composition of the curable composition. By way of non-limiting example, the radioisotope Pd-103 is included in the fourth composition as PdCl2 or Pd(HNO3)2Cl2, and the palladium in PdCl2 or Pd(HNO3)2Cl2 is Pd-103. Similarly, the radioisotope precursor Pd-102 is included in the fourth composition as PdCl2 or Pd(HNO3)2Cl2, and the palladium in PdCl2 or Pd(HNO3)2Cl2 is Pd-102. In some embodiments, the radioisotope is Pd-103 and is provided as PdCl2. In some embodiments, the radioisotope is Pd-103 and is provided as Pd(HNO3)2Cl2. In some embodiments, the radioisotope precursor is Pd-102 and is provided as PdCl2. In some embodiments, the radioisotope precursor is Pd-102 and is provided as Pd(HNO3)2Cl2. As another non-limiting example, the radioisotope Y-90 is included in the fourth composition as Y2O3, Y2S3, O 12 S3Y2 or YF3, and the yttrium in Y2O3, Y2S3, O 12 S3Y2 or YF3 is Y-90. Similarly, the radioisotope precursor Y-89 is included in the fourth composition as Y2O3, Y2S3, O 12 S3Y2 or YF3, and the yttrium in Y2O3, Y2S3, O 12 S3Y2 or YF3 is Y-89. The foregoing examples are illustrative only and are not meant to be limiting in any way. Those of ordinary skill in the art will readily recognize additional forms of radioisotopes provided herein for use in this composition. Such forms are within the scope of this disclosure.

[0057] In some embodiments, one or more radioisotopes of the fourth composition are produced by activating one or more radioisotope precursors before the curable composition is cured. In some embodiments, one or more radioisotopes of the fourth composition are produced by activating one or more radioisotope precursors after the curable composition is cured.

[0058] Thus, in some embodiments, a curable composition is provided that includes a first composition including one or more monomers, a second composition including one or more oligomers, a third composition capable of creating free radicals; and a fourth composition including one or more radioisotope precursors. The free radicals can be generated via known methods, and thus, the third composition can include any such components necessary to generate the free radicals. In some embodiments, the free radicals are generated through a chemical reaction occurring within the third composition. In some embodiments, the free radicals are generated when the third composition is exposed to radiation. The radiation can be ultraviolet light, infrared light, thermal radiation, or any other form of radiation used to promote curing / polymerization of the composition. In some embodiments, the radiation is ultraviolet light. In some embodiments, the radiation is infrared light. In some embodiments, the radiation is thermal radiation. In some embodiments, one or more monomers of the first composition include styrene, N-vinylpyrrolidone, acrylate, or mixtures thereof, where styrene is as provided herein and acrylate is as provided herein. In some embodiments, one or more oligomers of the second composition include epoxides (epoxide-containing compounds), urethanes, polyethers, polyesters, or any combination thereof, where the epoxide-containing compounds are as provided herein, urethanes are as provided herein, polyethers are as provided herein, and polyesters are as provided herein. In some embodiments, one or more radioisotope precursors are as provided herein.

[0059] In some embodiments, one or more radioisotope precursors are uniformly distributed throughout the curable composition. In some embodiments, one or more radioisotope precursors are not uniformly distributed throughout the curable composition. Without being bound by any particular theory, the radioisotope precursors of the present disclosure are spatially distributed throughout the curable composition such that some portion or portions of the composition contain a higher areal concentration of radioisotope precursors than other regions of the composition. Such compositions are useful, for example, for performing dosimetry of radiation that coincides with a particular treatment area.

[0060] In some embodiments, a curable composition is provided that includes a first composition that includes a monomer that is methyl acrylate, a second composition that includes an oligomer that is an acrylate, a third composition that is capable of creating free radicals when exposed to radiation, and a fourth composition that includes a radioisotope that is Pd-103. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0061] In some embodiments, a curable composition is provided that includes a first composition that includes a monomer that is methyl acrylate, a second composition that includes an oligomer that is an acrylate, a third composition that is capable of creating free radicals when exposed to radiation, and a fourth composition that includes a radioisotope that is Y-90. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0062] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope that is Sn-177m. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0063] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope that is Pd103 provided as PdCl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0064] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope that is Pd103 provided as Pd(HNO3)2Cl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0065] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition comprising a radioisotope that is Y-90 generated from Y-89. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0066] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition comprising a radioisotope that is Y-90 generated from Sr-90. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0067] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition comprising a radioisotope precursor that is Pd-102. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0068] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Pd-104. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0069] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Y-89. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0070] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Sr-90. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0071] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an oligomer that is acrylate, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Pd-102 provided as PdCl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0072] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an oligomer that is acrylate, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Pd-102 provided as Pd(HNO3)2Cl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0073] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an oligomer that is acrylate, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Pd-104 provided as PdCl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate.

[0074] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition capable of creating free radicals when exposed to radiation, and a fourth composition including a radioisotope precursor that is Pd-104 provided as Pd(HNO3)2Cl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is a urethane acrylate.

[0075] In some embodiments, the third composition of the curable composition includes any component necessary to generate free radicals. In some embodiments, the third composition of the curable composition includes a photoinitiator, which can be a photogenerated substance. Examples of such initiators include, but are not limited to, tert-butylperoxy neodecanoate, benzoyl peroxide, dicumyl peroxide, methyl ethyl ketone peroxide, lauryl peroxide, cyclohexanone peroxide, t-butyl perbenzoate, t-butyl hydroperoxide, t-butyl benzene hydroperoxide, cumene hydroperoxide, t-butyl peroctoate, azobis-isobutyronitrile, 2-t-butylazo-2-cyano-4-methylpentane, and 4-t-butylazo-4-cyano-valeric acid. In some embodiments, the photoinitiator is tert-butylperoxy neodecanoate. In some embodiments, the photoinitiator is benzoyl peroxide. In some embodiments, the photoinitiator is dicumyl peroxide. In some embodiments, the photoinitiator is methyl ethyl ketone peroxide. In some embodiments, the photoinitiator is lauryl peroxide. In some embodiments, the photoinitiator is cyclohexanone peroxide. In some embodiments, the photoinitiator is t-butyl perbenzoate. In some embodiments, the photoinitiator is t-butyl hydroperoxide. In some embodiments, the photoinitiator is t-butyl benzene hydroperoxide. In some embodiments, the photoinitiator is cumene hydroperoxide. In some embodiments, the photoinitiator is t-butyl peroctoate. In some embodiments, the photoinitiator is azobis-isobutyronitrile. In some embodiments, the photoinitiator is 2-t-butylazo-2-cyano-4-methylpentane. In some embodiments, the photoinitiator is 4-t-butylazo-4-cyano-valeric acid.In some embodiments, the composition comprises a combination of at least two photoinitiators, and the at least two photoinitiators are selected from tert-butyl peroxy neodecanoate, benzoyl peroxide, dicumyl peroxide, methyl ethyl ketone peroxide, lauryl peroxide, cyclohexanone peroxide, t-butyl perbenzoate, t-butyl hydroperoxide, t-butyl benzene hydroperoxide, cumene hydroperoxide, t-butyl peroctoate, azobisisobutyronitrile, 2-t-butylazo-2-cyano-4-methylpentane, and 4-t-butylazo-4-cyano-valeric acid, or any combination thereof.

[0076] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an oligomer that is an acrylate, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope that is Pd-103. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0077] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an oligomer that is an acrylate, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope that is Y-90. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0078] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope that is Sn-177m. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0079] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope that is Pd103 provided as PdCl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0080] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope that is Pd103 provided as Pd(HNO3)2Cl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0081] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition including a photoinitiator, and a fourth composition including a radioisotope that is Y-90 generated from Y-89. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0082] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition including a photoinitiator, and a fourth composition including a radioisotope that is Y-90 generated from Sr-90. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0083] In some embodiments, a curable composition is provided that includes a first composition including a monomer that is methyl acrylate, a second composition including an acrylate oligomer, a third composition including a photoinitiator, and a fourth composition including a radioisotope precursor that is Pd-102. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0084] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Pd-104. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0085] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Y-89. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0086] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Sr-90. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0087] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Pd-102 provided as PdCl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0088] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Pd-102 provided as Pd(HNO3)2Cl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0089] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an acrylate oligomer, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Pd-104 provided as PdCl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0090] In some embodiments, a curable composition is provided that includes a first composition comprising a monomer that is methyl acrylate, a second composition comprising an oligomer that is acrylate, a third composition comprising a photoinitiator, and a fourth composition comprising a radioisotope precursor that is Pd-104 provided as Pd(HNO3)2Cl2. In some embodiments, the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). In some embodiments, the acrylate oligomer is urethane acrylate. In some embodiments, the photoinitiator is as provided herein.

[0091] Also provided herein is a substantially cured composition comprising a polymer structure, prepared from a curable composition as provided herein. As used herein, "substantially cured" refers to a composition that is at least 50% cured. Thus, a substantially cured composition is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% cured.

[0092] Also provided herein is a substantially cured composition or a method of preparing a cured composition. In some embodiments, the method includes mixing a curable composition as provided herein and mixing the components under conditions sufficient to cure the composition. In some embodiments, the method includes mixing a curable composition as provided herein and exposing the curable composition to radiation to form a substantially cured composition or a cured composition. In some embodiments, the third composition of the curable composition includes a photoinitiator as provided herein. In some embodiments, the method includes exposing the composition to UV light or infrared light to initiate curing of the composition. In some embodiments, the composition is exposed at a wavelength of about 380 - 420 nm. In some embodiments, the composition is exposed at a wavelength of about 405 nm.

[0093] In some embodiments, the method is provided for preparing a multi-layer substantially cured composition or a cured composition. In some embodiments, the method includes mixing a curable composition as provided herein and exposing the curable composition to radiation to form a first layer of a substantially cured composition or a cured composition, thereby preparing a first layer of a substantially cured composition or a cured composition. In some embodiments, the method includes mixing a curable composition as provided herein, disposing the mixture on a first layer, and exposing the mixture to radiation to form a second layer of a substantially cured composition or a cured composition on the first layer, thereby preparing a second layer of a substantially cured composition or a cured composition on the first layer. This process can be repeated as many times as necessary to form a multi-layer composition. In some embodiments, the method is repeated to form 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 layers of the composition. In some embodiments, the substantially cured composition or the cured composition is a single layer of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is two layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is three layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is four layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is five layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is six layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is seven layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is eight layers of a substantially cured composition or a cured composition. In some embodiments, the substantially cured composition or the cured composition is nine layers of a substantially cured composition or a cured composition.In some embodiments, the substantially cured composition or the cured composition is a 10-layer substantially cured composition or cured composition. In some embodiments, the substantially cured composition or the cured composition includes more than 10 layers. In some embodiments, the method is repeated to form a 3-layer cured composition or substantially cured composition.

[0094] Accordingly, provided herein is a multi-layer cured composition or substantially cured composition prepared from the curable composition provided herein. In some embodiments, the composition includes 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 layers. In some embodiments, the composition includes 1 layer. In some embodiments, the composition includes 2 layers. In some embodiments, the composition includes 3 layers. In some embodiments, the composition includes 4 layers. In some embodiments, the composition includes 5 layers. In some embodiments, the composition includes 6 layers. In some embodiments, the composition includes 7 layers. In some embodiments, the composition includes 8 layers. In some embodiments, the composition includes 9 layers. In some embodiments, the composition includes 10 layers. In some embodiments, the composition includes 1, 2, 3, 4, 5, 6, 7, 8, 9, or more than 10 layers. In some embodiments, the composition includes 2 or more layers. In some embodiments, the composition includes 3 or more layers. In some embodiments, the composition includes 4 or more layers. In some embodiments, the composition includes 5 or more layers. In some embodiments, the composition includes 6 or more layers. In some embodiments, the composition includes 7 or more layers. In some embodiments, the composition includes 8 or more layers. In some embodiments, the composition includes 9 or more layers. In some embodiments, the composition includes 10 or more layers. In some embodiments, the composition includes 11 or more layers.

[0095] In some embodiments, the composition comprises from 1 to about 20 layers. In some embodiments, the composition comprises from about 2 to about 20 layers. In some embodiments, the composition comprises from about 3 to about 20 layers. In some embodiments, the composition comprises from about 4 to about 20 layers. In some embodiments, the composition comprises from about 5 to about 20 layers. In some embodiments, the composition comprises from about 6 to about 20 layers. In some embodiments, the composition comprises from about 7 to about 20 layers. In some embodiments, the composition comprises from about 8 to about 20 layers. In some embodiments, the composition comprises from about 9 to about 20 layers. In some embodiments, the composition comprises from about 10 to about 20 layers. In some embodiments, the composition comprises from about 11 to about 20 layers. In some embodiments, the composition comprises from about 12 to about 20 layers. In some embodiments, the composition comprises from about 13 to about 20 layers. In some embodiments, the composition comprises from about 14 to about 20 layers. In some embodiments, the composition comprises from about 15 to about 20 layers. In some embodiments, the composition comprises from about 16 to about 20 layers. In some embodiments, the composition comprises from about 17 to about 20 layers. In some embodiments, the composition comprises from about 18 to about 20 layers. In some embodiments, the composition comprises from about 19 to about 20 layers.

[0096] In some embodiments, the composition comprises from 1 to about 20 layers. In some embodiments, the composition comprises from 1 to about 19 layers. In some embodiments, the composition comprises from 1 to about 18 layers. In some embodiments, the composition comprises from 1 to about 17 layers. In some embodiments, the composition comprises from 1 to about 16 layers. In some embodiments, the composition comprises from 1 to about 15 layers. In some embodiments, the composition comprises from 1 to about 14 layers. In some embodiments, the composition comprises from 1 to about 13 layers. In some embodiments, the composition comprises from 1 to about 12 layers. In some embodiments, the composition comprises from 1 to about 11 layers. In some embodiments, the composition comprises from 1 to about 10 layers. In some embodiments, the composition comprises from 1 to about 9 layers. In some embodiments, the composition comprises from 1 to about 8 layers. In some embodiments, the composition comprises from 1 to about 7 layers. In some embodiments, the composition comprises from 1 to about 6 layers. In some embodiments, the composition comprises from 1 to about 5 layers. In some embodiments, the composition comprises from 1 to about 4 layers. In some embodiments, the composition comprises from 1 to about 3 layers. In some embodiments, the composition comprises from 1 to about 2 layers.

[0097] In some embodiments, a method of preparing a multilayer substantially cured composition or cured composition comprises preparing a first layer of a substantially cured composition or cured composition, including mixing a curable composition as provided herein and exposing the curable composition to radiation to form a first layer of a substantially cured composition or cured composition. In some embodiments, the method comprises preparing a second layer of a substantially cured composition or cured composition on the first layer, including mixing a curable composition as provided herein that includes a photoinitiator, disposing the mixture on the first layer, and exposing the mixture to radiation to form a second layer of a substantially cured composition or cured composition on the first layer. In some embodiments, the method comprises preparing a third layer of a substantially cured composition or cured composition on the second layer, including mixing a curable composition as provided herein that includes a photoinitiator, disposing the mixture on the second layer, and exposing the mixture to radiation to form a third layer of a substantially cured composition or cured composition on the first layer. As provided herein, this process can be repeated as many times as necessary to form a multilayer composition.

[0098] As provided herein, the curable composition of the present disclosure may contain radioisotopes or radioisotope precursors that are uniformly distributed throughout the composition, or may contain radioisotopes or radioisotope precursors with a non-uniform distribution. Thus, when creating a multi-layer substantially cured composition or cured composition by the method provided herein, in order to form a multi-layer substantially cured composition or cured composition, each layer may optionally omit the composition of the radioisotope or radioisotope precursor, and the radioisotope or radioisotope precursor of the multi-layer substantially cured composition or cured composition is such that one or more portions of the multi-layer substantially cured composition or cured composition contain a higher regional concentration of the radioisotope or radioisotope precursor than other regions of the multi-layer substantially cured composition or cured composition, spatially distributed. Such a multi-layer substantially cured composition or cured composition is useful, for example, for performing dosimetry of radiation that coincides with a particular treatment area.

[0099] Accordingly, in some embodiments, a method of preparing a multilayer substantially cured composition or cured composition comprises preparing a first layer of the substantially cured composition or cured composition, including mixing a curable composition as provided herein and exposing the curable composition to radiation to form a first layer of a substantially cured composition or cured composition; optionally mixing a curable composition comprising a photoinitiator as provided herein that does not contain a radioisotope or radioisotope precursor, disposing the mixture on the first layer, and exposing the mixture to radiation to form a second layer of a substantially cured composition or cured composition on the first layer; optionally mixing a curable composition comprising a photoinitiator as provided herein that does not contain a radioisotope or radioisotope precursor, disposing the mixture on the second layer, and exposing the mixture to radiation to form a third layer of a substantially cured composition or cured composition on the first layer, optionally including preparing a third layer of the substantially cured composition or cured composition on the second layer. As provided herein, this process can be repeated as many times as necessary to form a multilayer composition.

[0100] It should be understood that the methods described above are illustrative and are not intended to be limiting in any way. For example, the preparation of a substantially cured composition or a cured composition may include any necessary steps for initiating the process of curing or substantially curing the composition through the generation of free radicals in a third composition. In some embodiments, the free radicals are generated through a chemical reaction as provided herein. In some embodiments, the free radicals are generated when exposed to radiation as provided herein. It should also be understood that when fabricating a multi-layer substantially cured composition or a cured composition, each layer may not need to be exposed to an initiating catalyst (e.g., chemical reaction, radiation, etc.) to generate free radicals. Without being bound by any particular theory, the free radicals generated by the third composition initiate the process of curing or substantially curing the composition. Each successive layer may be exposed to an initiating catalyst (e.g., chemical reaction, radiation, etc.) to generate free radicals, or the free radicals generated during the process of curing or substantially curing the previous layer may themselves act as an initiating catalyst to cure or substantially cure the successive layer.

[0101] Thus, in some embodiments, a method of preparing a multilayer substantially cured composition or cured composition comprises preparing a first layer of a substantially cured composition or cured composition, including mixing a curable composition as provided herein and exposing the curable composition to radiation to form a first layer of a substantially cured composition or cured composition; preparing a second layer of a substantially cured composition or cured composition on the first layer, including mixing a curable composition as provided herein, optionally without a radioisotope or radioisotope precursor, disposing the mixture on the first layer, and optionally exposing the mixture to radiation, wherein free radicals generated during optional radiation or preparation of the previous layer initiate a process of forming a second layer of a substantially cured composition or cured composition on the first layer; and optionally preparing a third layer of a substantially cured composition or cured composition on the second layer, including mixing a curable composition as provided herein, optionally without a radioisotope or radioisotope precursor, disposing the mixture on the second layer, and optionally exposing the mixture to radiation, wherein free radicals generated during optional radiation or preparation of the previous layer initiate a process of forming a third layer of a substantially cured composition or cured composition on the first layer. As provided herein, this process can be repeated as many times as necessary to form a multilayer composition.

[0102] The compositions provided herein can also be prepared by additional processes, such as 3-D printing, to form compositions having specific three-dimensional structures or shapes. The shape can be based on the area being treated, such as a skin area or a lumen into which the composition is implanted.

[0103] Three-dimensional (3D or 3-D) printing is an additional printing process for creating three-dimensional objects from digital models. 3D printing technology is known as an additive process because it involves successive layers of material.

[0104] 3D printing technology is used in various industries with respect to manufacturing and planning. For example, the automotive, aerospace, and consumer goods industries use 3D printing to produce prototypes for parts and products. 3D printing is also used in the construction industry to print structural models. The use of 3D printing is also growing rapidly in civilian and government defense.

[0105] Therefore, 3-D printing can be used to create constructs (compositions) based on images of the area, cavity, surface, etc. of the subject to be treated. For example, conventional 3D printing enables the creation of an object by laminating materials one layer at a time on a flat manufacturing platform. After the first layer is laminated, the second layer is laminated, i.e., laminated on top of the first layer. This process is repeated as necessary to create a multi-layer solid article.

[0106] In some embodiments, a system is provided that includes a processor(s) configured to prepare a model of a construct (i.e., a cured composition or a substantially cured composition) manufactured by a 3-D printing system. The model construct can define, similar to the shape of the construct, the type(s) of material(s) included in the construct, and the location within the construct where each type of material is disposed. The shape of the construct can include a position-specific shape, such as a position-specific shape of a portion of the construct that mates with the subject or area of the subject to be treated. For example, a construct designed to mate with a portion of a subject having exposed skin or tissue is made using the compositions provided herein.

[0107] In some embodiments, the preparation of the model can include scanning an area of the subject (e.g., skin, tissue, cavity, etc.) from which the construct is to be obtained using a three-dimensional scanner. For example, a scanner is used to determine the topology of the area. The size or location of the construct is determined by scanning or through any other suitable means.

[0108] Alternatively or additionally, preparing the model may include downloading the model from a model repository or any other suitable source. The processor(s) may then fabricate a model of the construct based on the result.

[0109] In some embodiments, preparing the model of the construct is performed using off-the-shelf software, which may include software for “standard” scans, modeling, and / or printing. For example, common 3D model file formats are used to create tissue constructs in common 3D modeling and printing software.

[0110] In some embodiments, the area to be irradiated is determined by creating a dermoscopic image, which is then converted to a 3-D image and used to manufacture a construct through 3-D printing such that the area to be irradiated is specifically irradiated and healthy tissue is not substantially affected by the radiation. Other systems can be used to create 3-D images, which can then be used to fabricate constructs of appropriate size or positional specificity.

[0111] Accordingly, in some embodiments, a method of preparing a substantially cured composition or a cured composition is provided. In some embodiments, the method includes mixing a curable composition as provided herein, printing the composition with a 3-D printer into the three-dimensional structure of a target region, and exposing the composition to radiation to form a substantially cured composition or a cured composition in the shape or site-specificity of the three-dimensional structure of the target region. In some embodiments, the third composition of the curable composition includes a photoinitiator as provided herein. In some embodiments, the three-dimensional structure of the presented target region is prepared from the region of the subject to be treated using the cured composition. In some embodiments, the target region is the skin surface to be treated. In some embodiments, the target region is a bone, tissue, cavity, etc. of the subject. In some embodiments, the three-dimensional structure of the target region is determined by imaging the region of the subject to be treated using the cured composition and forming the dimensions / boundaries of the three-dimensional structure of the target region.

[0112] In some embodiments, a method of treating a subject using radiation is provided. In some embodiments, the method includes applying, implanting, contacting, etc., a cured composition or a substantially cured composition as provided herein onto or into the target region of the subject, or with the target region of the subject. In some embodiments, the target region is the skin surface to be treated. In some embodiments, the target region is a bone, tissue, cavity, etc. of the subject.

[0113] In some embodiments, a method of treating a subject having cancer is provided. In some embodiments, the method includes applying, implanting, contacting, etc., a cured composition or a substantially cured composition as provided herein onto or into the target area of the subject or together with the target area of the subject. In some embodiments, the target area is the skin surface to be treated. In some embodiments, the target area is the bone, tissue, cavity, etc. of the subject. In some embodiments, the cancer is skin cancer. In some embodiments, the skin cancer is malignant melanoma (MM), basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). In some embodiments, the skin cancer is MM. The cured composition or the substantially cured composition can be prepared by the methods provided herein.

[0114] Enumeration of embodiments: In some embodiments, the following embodiments are provided: 1. A curable composition comprising: a first composition comprising one or more monomers, a second composition comprising one or more oligomers; and a third composition capable of creating free radicals; and a fourth composition comprising one or more radioisotopes A curable composition. 2. The curable composition according to embodiment 1, wherein one or more radioisotopes in the fourth composition are produced by activating one or more radioisotope precursors. 3. The curable composition according to embodiment 2, wherein one or more radioisotope precursors are activated after the curable composition is cured to produce one or more radioisotopes. 4. The curable composition according to any one of embodiments 1 to 3, wherein one or more radioisotopes are present in an amount sufficient to be detected by an image processing processor. 5. The curable composition according to any one of embodiments 1 to 4, wherein one or more radioisotopes are present in an amount sufficient to be detected and located. 6. The sclerosing composition according to any one of embodiments 1 to 5, wherein one or more radioisotopes are present in an amount sufficient to deliver a therapeutic dose of radiation to a mammal. 7. The sclerosing composition according to any one of embodiments 1 to 6, wherein one or more radioisotopes include diagnostic isotopes, therapeutic isotopes, or combinations thereof. 8. The sclerosing composition according to embodiment 7, wherein the diagnostic or therapeutic isotope is present in an amount sufficient to be detected and located. 9. The sclerosing composition according to embodiment 7 or 8, wherein the diagnostic radioisotope is present in an amount sufficient to be detected by an image processing processor. 10. The sclerosing composition according to any one of embodiments 7 to 9, wherein the therapeutic radioisotope is present in an amount sufficient to deliver a therapeutic dose of radiation to a mammal. 11. The sclerosing composition according to any one of embodiments 1 to 10, wherein one or more radioisotopes are uniformly distributed throughout the composition. 12. The sclerosing composition according to any one of embodiments 1 to 10, wherein one or more radioisotopes are not uniformly distributed throughout the composition. 13. The sclerosing composition according to any one of embodiments 1 to 12, wherein the third composition creates free radicals through a chemical reaction. 14. The sclerosing composition according to any one of embodiments 1 to 12, wherein the third composition creates free radicals when exposed to radiation. 15. The sclerosing composition according to embodiment 14, wherein the radiation is thermal radiation, ultraviolet light, infrared light, or the like. 16. A sclerosing composition comprising: a first composition comprising one or more monomers, a second composition comprising one or more oligomers; and a third composition capable of creating free radicals when exposed to radiation (e.g., ultraviolet light, infrared light, etc.); and a fourth composition comprising one or more radioisotope precursors The sclerosing composition comprising. 17. The curable composition according to embodiment 16, wherein one or more radioisotope precursors in the fourth composition are activated to produce one or more radioisotopes. 18. The curable composition according to embodiment 17, wherein one or more radioisotope precursors are activated after the curable composition is cured to produce one or more radioisotopes. 19. The curable composition according to any one of embodiments 16 to 18, wherein one or more radioisotope precursors are present in an amount sufficient to produce one or more radioisotopes in an amount sufficient to be detected by an image processing processor. 20. The curable composition according to any one of embodiments 16 to 19, wherein one or more radioisotope precursors are present in an amount sufficient to produce one or more radioisotopes in an amount sufficient to be detected and located. 21. The curable composition according to any one of embodiments 16 to 20, wherein one or more radioisotope precursors are present in an amount sufficient to produce one or more radioisotopes in an amount sufficient to deliver a therapeutic dose of radiation to a mammal. 22. The curable composition according to any one of embodiments 16 to 21, wherein one or more radioisotope precursors are activated to produce a diagnostic radioisotope, a therapeutic radioisotope, or a combination thereof. 23. The curable composition according to embodiment 22, wherein one or more radioisotope precursors are present in an amount sufficient to produce a diagnostic radioisotope, a therapeutic radioisotope, or a combination thereof in an amount sufficient to be detected and located. 24. The curable composition according to embodiment 22 or 23, wherein one or more radioisotope precursors are present in an amount sufficient to produce a diagnostic radioisotope in an amount sufficient to be detected by an image processing processor. 25. The composition according to any one of embodiments 22 to 24, wherein one or more radioisotope precursors are present in an amount sufficient to produce a therapeutic radioisotope in an amount sufficient to deliver a therapeutic dose of radiation to a mammal. 26. The curable composition according to any one of embodiments 16 to 25, wherein one or more radioisotope precursors are uniformly distributed throughout the composition. 27. The curable composition according to any one of embodiments 16 to 25, wherein one or more radioisotope precursors are not uniformly distributed throughout the composition. 28. The curable composition according to any one of embodiments 16 to 27, wherein the third composition creates free radicals through a chemical reaction. 29. The curable composition according to any one of embodiments 16 to 27, wherein the third composition creates free radicals when exposed to radiation. 30. The radiation is thermal radiation or ultraviolet light, and the curable composition according to embodiment 29. 31. The curable composition according to any one of embodiments 1 to 30, which is biocompatible. 32. The curable composition according to any one of embodiments 1 to 31, which is bioabsorbable. 33. The curable composition according to any one of embodiments 1 to 32, further comprising one or more therapeutic agents. 34. The curable composition according to embodiment 33, wherein the one or more therapeutic agents are anti-cancer agents, anti-viral agents, antibacterial agents, antifungal agents, pain management agents, immunosuppressive agents, radiosensitizers, anti-inflammatory agents, or combinations thereof. 35. The curable composition according to any one of embodiments 1 to 34, wherein the first composition comprises styrene, N-vinylpyrrolidone, acrylate, or a mixture thereof. 36. Styrene is the curable composition according to embodiment 35, which is 3-vinylphenylboronic acid, 1-vinylnaphthalene, 4-vinylbenzylamine, vinyltoluene monomer, 2,2'-(2-vinylanthracene-9,10-diylidene)bis(1,3-dithiol), 4-tert-butylstyrene, 2,3,4,5,6-pentafluorostyrene, 3-aminostyrene, 3-bromostyrene, 2-vinylanthraquinone, 4-fluoro-α-methylstyrene, 4-chlorostyrene, 2-chlorostyrene, chloromethylstyrene, 9-vinylanthracene, sodium p-styrenesulfonate hydrate, 4-methoxystyrene, 2-bromostyrene, 4-bromo-β,β-difluorostyrene, 3-fluorostyrene, 4-n-octylstyrene, 2,2'-(2-vinylanthracene-9,10-diylidene)dimalononitrile, divinylbenzene, 4-(chloromethyl)styrene, 2-vinylphenyl acetate, 3-chlorostyrene, vinylbenzyl cyanide, 3-(trifluoromethyl)styrene, 2,4,6-trimethylstyrene, trimethoxy(4-vinylphenyl)silane, 2-methylstyrene, 4-methylstyrene, 4-vinylbiphenyl, 4-isopropenyltoluene, 4-tert-butoxystyrene, 1-(1-ethoxyethoxy)-4-vinylbenzene, trimethyl(4-vinylphenyl)silane, 4-vinylphenyl acetate, α-methylstyrene, styrene, 4-aminostyrene, 4-fluorostyrene, 4-(trifluoromethyl)styrene, diphenyl(4-vinylphenyl)phosphine, 4-vinylbenzoic acid, 4-vinylphenylboronic acid, 4-nitrostyrene, 4-bromostyrene, 3-methylstyrene, or any combination thereof. 37. The oligomer of the second composition is the curable composition according to any one of embodiments 1 to 36, which contains an epoxide, a urethane, a polyether, a polyester, or any combination thereof. 38. The composition containing one or more radioisotopes is the curable composition according to any one of embodiments 1 to 37, which is in the form of a solution, a colloid, a microfiber, a microsphere, a nanotube, or a nanoparticle. 39. One or more radioisotopes are Pd-103, Pd-109, I-125, I-124, I-123, I-131, P-32, Y-90, Ac-225, Cs-131, B-10, Ir-192, Sn-177m, Ho-166, Cu-64, Cu-67, Re-186, Re-188, Ga-67, Ga-68, In-111, Co-60, Cs-137, Lu-177, Yb-169, Er-169, Au-198, Sm-153, Am-241, Sr-89, Ra-223, Pb-212, Bi-213, Tc-99, At-211, Cf-252, or any combination thereof, the curable composition according to any one of Embodiments 1 to 38. 40. One or more radioisotopes are Pd-103, P-32, Y-90, or Sn-177m, the curable composition according to any one of Embodiments 1 to 34. 41. One or more radioisotope precursors are Xe-124, S-32, Y-89, Sr-90, Th-229, Ir-191, Ir-193, Dy-164, Pd-102, Pd-104, Pd-108, B-10, P-31, Ni-64, Zn-67, Zn-68, Zn-70, Rh-103, Te-125, Ba-103, Cs-133, Te-124, Th-232, Sr-86, Er-168, Cd-111, Cd-112, W-186, Bi-209, Tm-169, Yb-176, Ra-226, or any combination thereof, the curable composition according to any one of Embodiments 2 to 40. 42. One or more radioisotope precursors are selected from Pd-102, Pd-104, P-31, or Y-89, the curable composition according to Embodiment 40. 43. The monomer is methyl acrylate, the oligomer is acrylate, and one or more radioisotopes are Pd-103, the curable composition according to any one of Embodiments 1 to 42. 43A. Methyl acrylate is 2-hydroxyethyl methacrylate (HEMA), the curable composition according to Embodiment 43. 44. The curable composition according to embodiment 43 or 43A, wherein the acrylate oligomer is a urethane acrylate. 45. The curable composition according to any one of embodiments 1 to 44, wherein the monomer is methyl acrylate, the oligomer is an acrylate, and the one or more radioisotope precursors are Pd-102 or Pd-104. 46. The curable composition according to embodiment 45, wherein the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA). 47. The curable composition according to embodiment 45 or 46, wherein the acrylate oligomer is a urethane acrylate. 48. The curable composition according to any one of embodiments 1 to 47, wherein the third composition comprises a photoinitiator that can be a photogenerated substance. 49. The curable composition according to embodiment 48, wherein the photoinitiator is tert-butyl peroxyneodecanoate, benzoyl peroxide, dicumyl peroxide, methyl ethyl ketone peroxide, lauryl peroxide, cyclohexanone peroxide, t-butyl perbenzoate, t-butyl hydroperoxide, t-butyl benzene hydroperoxide, cumene hydroperoxide, t-butyl peroctoate, azobis-isobutyronitrile, 2-t-butylazo-2-cyano-4-methylpentane, and 4-t-butylazo-4-cyano-valeric acid, or any combination thereof. 50. A substantially cured composition comprising a polymer structure prepared from the curable composition according to any one of embodiments 1 to 49. 51. A method for preparing a substantially cured composition, comprising mixing the curable composition according to any one of embodiments 1 to 49 and exposing the curable composition to radiation to form a substantially cured composition. 52. Preparing a first layer of a substantially cured composition, comprising mixing the curable composition according to any one of embodiments 1 to 49 and exposing the curable composition to radiation to form a first layer of a substantially cured composition; Mixing the curable composition according to any one of Embodiments 1 to 49 with a photoinitiator, disposing the mixture on the first layer, and exposing the mixture to radiation to form a second layer of a substantially cured composition on the first layer, preparing a second layer of a substantially cured composition on the first layer; Optionally, then mixing the curable composition according to any one of Embodiments 1 to 49 with a photoinitiator, disposing the mixture on the second layer, and exposing the mixture to radiation to form a third layer of a substantially cured composition on the second layer, preparing a third layer of a substantially cured composition on the second layer The method according to Embodiment 51, comprising: 53. A method for preparing a substantially cured composition, comprising mixing the curable composition according to any one of Embodiments 1 to 49, printing the composition in a three-dimensional structure of a target region with a 3-D printer, and curing the composition by exposing the composition to radiation to form a substantially cured composition in the shape of the three-dimensional structure of the target region. 54. The method according to Embodiment 53, wherein the three-dimensional structure of the presented target region is prepared from a region of a subject to be treated using the cured composition. 55. The method according to Embodiment 54, wherein the three-dimensional structure of the target region is determined by imaging a region of a subject to be treated using the cured composition and forming the dimensions / boundaries of the three-dimensional structure of the target region. 56. A method for treating a subject using radiation, comprising applying, implanting, contacting, etc. a cured composition prepared from any one of Embodiments 1 to 49. 57. The method according to Embodiment 56, wherein the cured composition is prepared by the method according to any one of Embodiments 51 to 55. 58. The method according to any one of Embodiments 51 to 57, wherein the third composition of the curable composition contains a photoinitiator. 59. The photoinitiator is tert-butyl peroxy neodecanoate, benzoyl peroxide, dicumyl peroxide, methyl ethyl ketone peroxide, lauryl peroxide, cyclohexanone peroxide, t-butyl perbenzoate, t-butyl hydroperoxide, t-butyl benzene hydroperoxide, cumene hydroperoxide, t-butyl peroctoate, azobisisobutyronitrile, 2-t-butylazo-2-cyano-4-methylpentane, and 4-t-butylazo-4-cyano-valeric acid, or any combination thereof, in the method of embodiment 58.

Examples

[0115] The following examples of the compounds, compositions and methods described herein are illustrative and not limiting. Other suitable modifications and adaptations known to those skilled in the art are within the scope of the following embodiments.

Examples

[0116] Preparation of a composition containing a radiation source. 10 grams of PdCl2 (disks were manufactured using elemental palladium. For the production of therapeutic disks, an equivalent mass of elemental palladium was replaced with an appropriate amount of the mass of Pd-103) was charged into an ion exchange column containing 50 grams of resin, and then stripped with concentrated ammonium hydroxide to obtain a Pd amine with a concentration of 6.363 g / L that forms Pd(NH3)2Cl2. Using DecorRom UV resin-Clear, when 2.33 grams of DecorRom resin and 600 uL of Pd(NH3)2Cl2 solution were mixed for approximately 2 minutes, the resulting solution was uniformly yellow. The concentration of the resulting solution was 1276 μg Pd / 1 gram of solution. Next, this solution was cured into a layered disk three-dimensional structure with ANYCUBE Wash&Cure. Using a silicon mold with a diameter of 20 mm and a depth of 1 mm, a disk was formed. A total of 0.51 grams of the mixture from the above was added, and each layer was cured for 4 minutes to be cured into three layers. The disk was found to be a stable solid with a disk diameter of 20 mm, a height of 1 mm, and a weight of 0.51 grams; the palladium content was approximately 651 μg (calculated value), and the Pd-103 activity was 46 curies (calculated value). The cured composition was uniformly light orange.

Example

[0117] 3-D printing of a composition containing a radiation source. In this example, a 3-D printed disk was manufactured using elemental palladium, and for the manufacture of the therapeutic disk, an equivalent mass of elemental palladium was replaced with an appropriate amount of the mass of Pd-103. 10 grams of PdCl2 was introduced into an ion exchange column containing 50 grams of resin, and then stripped with concentrated ammonium hydroxide to obtain Pd amine, which is Pd(NH3)2Cl2 with a concentration of 6.363 g / L. The disk was printed using Weistek 3D printer resin, which is a 405 nm LCD UV curable photopolymer resin. Briefly, when 45 mL of the Weistek 3D printing resin and 5 mL of the Pd(NH3)2Cl2 solution were mixed for approximately 8 minutes, the resulting solution was a uniform milky white. The concentration of the resulting solution was 470 μg Pd / gram of solution. 3D printing was carried out by laminating the above solution into a disk three-dimensional structure using an ANYCUBE PHOTON S 405 nm UV wavelength printer. The laminated disk solution was washed with ANYCUBE Wash&Cure and then with isopropyl alcohol, and then cured with ANYCUBE Wash&Cure. The manufactured disk was a stable solid with a disk diameter of 20.2 mm, a height of 1.6 mm, and a weight of 0.59 grams. The palladium content was approximately 278 μg (calculated value), the Pd-103 volume was 20 curies (calculated value), and it was a uniform milky white.

Example

[0118] Preparation of a composition containing a radiation source. In this example, the disk was manufactured using glass microspheres containing the element yttrium, and for the production of the therapeutic disk, an appropriate amount of yttrium would be activated to Y-90. When 1.24 g of DecorRom UV Resin-Clear and 250 mg of glass microspheres containing approximately 79 mg of Y-89 were mixed for approximately 2 minutes, the resulting solution was colorless and opaque. The microspheres may be glass or other materials, and although not limited, they can be formulated to contain several therapeutic isotopes such as Y-90, P-32, and Ho-166. Using a silicon mold with a diameter of 20 mm and a depth of 1 mm, a disk was formed. A total of 0.50 g of the solution from the above was added as a single layer and cured using ANYCUBE Wash&Cure for 4 minutes. The disk was found to be solid and stable (disk diameter 20 mm, height 1 mm, weight 0.51 g), the Y-89 content was approximately 29 mg (calculated value), and the Y-90 activity was 160 mCi (calculated value). The cured composition was uniformly colorless and opaque.

Example

[0119] Preparation of a composition containing a radiation source. In this example, the disk was manufactured using a tin colloid containing the stable element tin, and for the production of the therapeutic disk, an appropriate amount of Sn-117m would be replaced with stable tin. When 1.09 grams of DecorRom UV Resin-Clear and 410 mg of a tin colloid containing approximately 1.22 mg of natural tin were mixed for approximately 2 minutes, the resulting solution was colorless and opaque. Using a silicon mold with a diameter of 20 mm and a depth of 1 mm, a disk was formed. A total of 0.50 g of the solution from the above was added as a single layer and cured using ANYCUBE Wash&Cure for 4 minutes. The disk was found to be solid and stable (disk diameter 20 mm, height 1 mm, weight 0.51 g), the tin content was approximately 1.22 mg (calculated value), and the Sn-117m activity was approximately 96 Ci (calculated value). The cured composition was uniformly colorless and opaque.

Example

[0120] Preparation of a composition having spatially distributed radioisotopes. Fabrication via a multilayer composition. Using a silicon mold as in previous examples, a first disk layer containing an effective amount of a radioisotope or radioisotope precursor as provided herein was fabricated. A continuous layer was added on top of the first layer, and the continuous layer contained little or no radioisotope or radioisotope precursor. The resulting multilayer disk contained a cured composition or substantially cured composition having spatially distributed radioisotopes or radioisotope precursors.

[0121] Fabrication via 3-D printing. The target tissue region was imaged to create a 3-D map of the target region. A mold of the desired shape was 3-D printed, and a layer of a curable composition as provided herein was added to the mold. Each layer may have the same or different concentrations of a radioisotope or radioisotope precursor. When each layer has a different concentration of a radioisotope or radioisotope precursor, a multilayer cured composition or substantially cured composition having spatially distributed radioisotopes or radioisotope precursors was fabricated.

[0122] Alternatively, a desired concentration of a radioisotope or radioisotope precursor was added to a 3-D printing resin, and a 3-D printer was used to print each layer of a cured composition or substantially cured composition. A plurality of compositions having the concentration of an individual radioisotope or radioisotope precursor were provided such that the 3-D printer printed a cured composition or substantially cured composition having spatially distributed radioisotopes or radioisotope precursors.

Examples

[0123] A patient with melanoma received a doctor's examination. The melanoma was imaged to create a 3-D map of the target tissue area. Using the 3-D map, a hardened composition containing a radiation source as provided herein and exemplified in Examples 1-4 was created. The hardened composition containing the radiation source was applied to the patient's melanoma and treated with radiation from the composition without substantially irradiating the healthy tissue surrounding the melanoma.

[0124] This example demonstrated that a sclerosing composition containing a radiation source can be fabricated in a specific three-dimensional structure and used for the treatment as provided herein.

[0125] Each and every patent, patent application disclosure, and publication cited herein is hereby incorporated by reference in its entirety. Although various embodiments have been disclosed with reference to specific aspects, it is clear that other aspects and modifications of these embodiments can be devised by those skilled in the art without departing from the true spirit and scope of this embodiment. The appended claims are intended to be construed to include all such aspects and equivalent modifications.

Claims

**Claim 1** A curable composition comprising: a first composition containing one or more monomers, a second composition containing one or more oligomers; and a third composition capable of creating free radicals; and a fourth composition containing one or more radioisotopes is a curable composition. **Claim 2** The curable composition according to claim 1, wherein one or more radioisotopes in the fourth composition are produced by activating one or more radioisotope precursors. **Claim 3** The curable composition according to claim 2, wherein one or more radioisotope precursors are activated after the curable composition is cured to produce one or more radioisotopes. **Claim 4** The curable composition according to claim 1, wherein one or more radioisotopes include diagnostic isotopes and therapeutic isotopes. **Claim 5** The curable composition according to claim 4, wherein the diagnostic radioisotope is present in an amount sufficient to be detected and located. **Claim 6** The curable composition according to claim 4, wherein the therapeutic radioisotope is present in an amount sufficient to deliver a therapeutic dose of radiation to a mammal. **Claim 7** The curable composition according to claim 1, wherein one or more radioisotopes are not uniformly distributed throughout the composition. **Claim 8** The curable composition according to claim 1, wherein the third composition creates free radicals through a chemical reaction or when exposed to radiation, and the radiation is thermal radiation, ultraviolet light, or infrared light. **Claim 9** The curable composition according to claim 1, which is biocompatible. **Claim 10** The curable composition according to claim 1, which is bioabsorbable. **Claim 11** The curable composition according to claim 1, further comprising one or more therapeutic agents, and the one or more therapeutic agents are anti-cancer agents, anti-viral agents, antibacterial agents, antifungal agents, pain management agents, immunosuppressive agents, radiation sensitizers, anti-inflammatory agents, or combinations thereof. **Claim 12** The curable composition according to claim 1, wherein the first composition comprises styrene, N-vinylpyrrolidone, acrylate, or mixtures thereof. **Claim 13** The styrene is 3-vinylphenylboronic acid, 1-vinylnaphthalene, 4-vinylbenzylamine, vinyltoluene monomer, 2,2'-(2-vinylanthracene-9,10-diylidene)bis(1,3-dithiol), 4-tert-butylstyrene, 2,3,4,5,6-pentafluorostyrene, 3-aminostyrene, 3-bromostyrene, 2-vinylanthraquinone, 4-fluoro-α-methylstyrene, 4-chlorostyrene, 2-chlorostyrene, chloromethylstyrene, 9-vinylanthracene, sodium p-styrenesulfonate hydrate, 4-methoxystyrene, 2-bromostyrene, 4-bromo-β,β-difluorostyrene, 3-fluorostyrene, 4-n-octylstyrene, 2,2'-(2-vinylanthracene-9,10-diylidene)dimalononitrile, divinylbenzene, 4-(chloromethyl)styrene, 2-vinylphenyl acetate, 3-chlorostyrene, vinylbenzyl cyanide, 3-(trifluoromethyl)styrene, 2,4,6-trimethylstyrene, trimethoxy(4-vinylphenyl)silane, 2-methylstyrene, 4-methylstyrene, 4-vinylbiphenyl, 4-isopropenyltoluene, 4-tert-butoxystyrene, 1-(1-ethoxyethoxy)-4-vinylbenzene, trimethyl(4-vinylphenyl)silane, 4-vinylphenyl acetate, α-methylstyrene, styrene, 4-aminostyrene, 4-fluorostyrene, 4-(trifluoromethyl)styrene, diphenyl(4-vinylphenyl)phosphine, 4-vinylbenzoic acid, 4-vinylphenylboronic acid, 4-nitrostyrene, 4-bromostyrene, 3-methylstyrene, or any combination thereof, the curable composition according to claim 12.

14. The oligomer of the second composition comprises an epoxide, urethane, polyether, polyester, or any combination thereof, the curable composition according to claim 1.

15. The composition comprising one or more radioisotopes is in the form of a solution, colloid, microfiber, microsphere, nanotube, or nanoparticle, the curable composition according to claim 1.

16. The curable composition according to claim 1, wherein the one or more radioisotopes are Pd-103, Pd-109, I-125, I-124, I-123, I-131, P-32, Y-90, Ac-225, Cs-131, B-10, Ir-192, Sn-177m, Ho-166, Cu-64, Cu-67, Re-186, Re-188, Ga-67, Ga-68, In-111, Co-60, Cs-137, Lu-177, Yb-169, Er-169, Au-198, Sm-153, Am-241, Sr-89, Ra-223, Pb-212, Bi-213, Tc-99, At-211, Cf-252, or any combination thereof.

17. The curable composition according to claim 2, wherein the radioisotope precursor is Xe-124, S-32, Y-89, Sr-90, Th-229, Ir-191, Ir-193, Dy-164, Pd-102, Pd-104, Pd-108, B-10, P-31, Ni-64, Zn-67, Zn-68, Zn-70, Rh-103, Te-125, Te-124, Ba-130, Cs-133, Th-232, Sr-86, Er-168, Cd-111, Cd-112, W-186, Bi-209, Tm-169, Yb-176, Ra-226, or any combination thereof.

18. The curable composition according to claim 1, wherein the monomer is methyl acrylate, the oligomer is acrylate, and the one or more radioisotopes are Pd-103.

19. The curable composition according to claim 18, wherein the methyl acrylate is 2-hydroxyethyl methacrylate (HEMA) and the acrylate oligomer is urethane acrylate.

20. The third composition contains a photoinitiator, and the photoinitiator is tert-butylperoxyneodecanoate, benzoyl peroxide, dicumyl peroxide, methyl ethyl ketone peroxide, lauryl peroxide, cyclohexanone peroxide, t-butyl perbenzoate, t-butyl hydroperoxide, t-butylbenzene hydroperoxide, cumene hydroperoxide, t-butyl peroctoate, azobisisobutyronitrile, 2-t-butylazo-2-cyano-4-methylpentane, and 4-t-butylazo-4-cyano-valeric acid, or any combination thereof, the curable composition according to claim 1.

21. A substantially cured composition comprising a polymer structure prepared from the curable composition according to claim 1.

22. A method for preparing a substantially cured composition, comprising mixing the curable composition according to claim 1 and exposing the curable composition to radiation to form a substantially cured composition.

23. Preparing a first layer of a substantially cured composition, comprising mixing the curable composition according to claim 1 and exposing the curable composition to radiation to form a first layer of a substantially cured composition; Preparing a second layer of a substantially cured composition on the first layer, comprising mixing the curable composition according to claim 1 and a photoinitiator, disposing the mixture on the first layer, and exposing the mixture to radiation to form a second layer of a substantially cured composition on the first layer; Optionally, preparing a third layer of a substantially cured composition on the second layer, comprising mixing the curable composition according to claim 1 and a photoinitiator, disposing the mixture on the second layer, and exposing the mixture to radiation to form a third layer of a substantially cured composition on the second layer The method according to claim 22.

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