Brachytherapy seed

Abstract

A radiopaque brachytherapy seed for implantation into a subject includes a biocompatible component, a therapeutically active component including a non-radioactive drug, and a radiopaque marker. The biocompatible component is (a) physically associated with a therapeutically active component and (b) in contact with the radiopaque marker. The brachytherapy seed has a size and shape suitable for passing through the bore of a needle having an interior diameter of less than about 2.7 millimeters (10 gauge).

1 . A brachytherapy seed for implantation into a subject comprising a biocompatible component, a therapeutically active component comprising a non-radioactive drug, and a radiopaque marker, said biocompatible component being (a) physically associated with a therapeutically active component and (b) in contact with said radiopaque marker, wherein said brachytherapy seed has a size and shape suitable for passing through the bore of a needle having an interior diameter of less than about 2.7 millimeters (10 gauge). 
     
     
         2 . The brachytherapy seed of  claim 1 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 1.4 millimeters (15 gauge). 
     
     
         3 . The brachytherapy seed of  claim 2 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 0.84 millimeters (18 gauge). 
     
     
         4 . The brachytherapy seed of  claim 2 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 0.56 millimeters (24 gauge). 
     
     
         5 . The brachytherapy seed of  claim 1 , wherein the seed is shaped into a cylinder having a diameter of between about 0.5 to 3 millimeters and a length 4 to 10 millimeters. 
     
     
         6 . The brachytherapy seed of  claim 5 , wherein the diameter is about 0.8 millimeters and the length is about 4.5 millimeters. 
     
     
         7 . The brachytherapy seed of  claim 1 , wherein the biocompatible component is non-biodegradable. 
     
     
         8 . The brachytherapy seed of  claim 1 , wherein the biocompatible component is biodegradable. 
     
     
         9 . The brachytherapy seed of  claim 8 , wherein the biodegradable biocompatible component comprises a polymer selected from the group consisting of: poly(bis(p-carboxyphenoxy) propane anhydride); poly(bis(p-carboxy) methane anhydride); poly(D,L-lactic-coglycolic acid); poly(isobutylcyanoacrylate); a copolymer of poly-carboxyphenoxypropane and sebacic acid; open cell polylactic acid; a co-polymer of a poly-fatty acid dimer and sebacic acid; poly(carboxyphenoxy) hexane; poly-1,4-phenylene dipropionic acid; polyisophthalic acid; and polydodecanedioic acid. 
     
     
         10 . The brachytherapy seed of  claim 1 , wherein the drug is selected from the group consisting of: stimulating and growth factors; gene vectors; viral vectors; anti-angiogenesis agents; cytostatic, cytotoxic, and cytocidal agents; transforming agents; apoptosis-inducing agents; radiosensitizers; radioprotectants; hormones; enzymes; antibiotics; antiviral agents; mitogens; cytokines; anti-inflammatory agents; immunotoxins; antibodies; and antigens. 
     
     
         11 . The brachytherapy seed of  claim 10 , wherein the drug is an anti-neoplastic agent. 
     
     
         12 . The brachytherapy seed of  claim 11 , wherein the anti-neoplastic agent is selected from the group consisting of: paclitaxel, 5-fluorouracil, and cisplatin. 
     
     
         13 . The brachytherapy seed of  claim 10 , wherein the drug is a radiosensitizing agent. 
     
     
         14 . The brachytherapy seed of  claim 13 , wherein the radiosensitizing agent is selected from the group consisting of: 5-fluorouracil, etanidazole, tirapazamine, BUdR, and IUdR. 
     
     
         15 . The brachytherapy seed of  claim 1 , wherein the radiopaque marker is comprised of a substance selected from the group consisting of: platinum, iridium, rhenium, gold, tantalum, bismuth, indium, tungsten, silver, and radiopaque polymers. 
     
     
         16 . The brachytherapy seed of  claim 1 , wherein the radiopaque marker is biodegradable. 
     
     
         17 . The brachytherapy seed of  claim 1 , wherein the therapeutically active substance further comprises a radioisotope. 
     
     
         18 . The brachytherapy seed of  claim 1 , wherein the biocompatible component and the therapeutically active substance are formed into a plurality of microspheres. 
     
     
         19 . The brachytherapy seed of  claim 18 , wherein the microspheres are biodegradable. 
     
     
         20 . The brachytherapy seed of  claim 1 , wherein the seed further comprises magnetic elements. 
     
     
         21 . The brachytherapy seed of  claim 1 , wherein the brachytherapy seed features a cavity. 
     
     
         22 . The brachytherapy seed of  claim 21 , wherein the cavity is filled with a hydrogel. 
     
     
         23 . The brachytherapy seed of  claim 1 , wherein the brachytherapy seed is fashioned into a cylindrical tube defining a lumen, the lumen having a first opening at a first end of the cylinder and a second opening at a second end of the cylinder different from the first end of the cylinder. 
     
     
         24 . The brachytherapy seed of  claim 23 , wherein the lumen is filled with a hydrogel. 
     
     
         25 . A brachytherapy seed for implantation into a subject comprising a non-metal biocompatible component, a therapeutically active component comprising a radioisotope, and a radiopaque marker, said biocompatible component being (a) physically associated with a therapeutically active component and (b) in contact with said radiopaque marker, wherein said brachytherapy seed has a size and shape suitable for passing through the bore of a needle having an interior diameter of less than about 2.7 millimeters (10 gauge). 
     
     
         26 . The brachytherapy seed of  claim 25 , wherein the radioisotope is contained within a non-radioactive biodegradable component. 
     
     
         27 . The brachytherapy seed of  claim 25 , wherein the radioisotope is contained within a non-radioactive non-biodegradable component. 
     
     
         28 . The brachytherapy seed of  claim 25 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 1.4 millimeters (15 gauge). 
     
     
         29 . The brachytherapy seed of  claim 25 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 0.84 millimeters (18 gauge). 
     
     
         30 . The brachytherapy seed of  claim 25 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 0.56 millimeters (24 gauge). 
     
     
         31 . The brachytherapy seed of  claim 25 , wherein the seed is shaped into a cylinder having a diameter of between about 0.5 to 3 millimeters and a length 4 to 10 millimeters. 
     
     
         32 . The brachytherapy seed of  claim 31 , wherein the diameter is about 0.8 millimeters and the length is about 4.5 millimeters. 
     
     
         33 . The brachytherapy seed of  claim 25 , wherein the biocompatible component is non-biodegradable. 
     
     
         34 . The brachytherapy seed of  claim 25 , wherein the biocompatible component is biodegradable. 
     
     
         35 . The brachytherapy seed of  claim 34 , wherein the biodegradable biocompatible component comprises a polymer selected from the group consisting of poly(bis(p-carboxyphenoxy) propane anhydride); poly(bis(p-carboxy) methane anhydride); poly(D,L-lactic-coglycolic acid); poly(isobutylcyanoacrylate); a copolymer of poly-carboxyphenoxypropane and sebacic acid; open cell polylactic acid; a co-polymer of a poly-fatty acid dimer and sebacic acid; poly(carboxyphenoxy) hexane; poly-1,4-phenylene dipropionic acid; polyisophthalic acid; and polydodecanedioic acid. 
     
     
         36 . The brachytherapy seed of  claim 25 , wherein the drug is selected from the group consisting of: stimulating and growth factors; gene vectors; viral vectors; anti-angiogenesis agents; cytostatic, cytotoxic, and cytocidal agents; transforming agents; apoptosis-inducing agents; radiosensitizers; radioprotectants; hormones; enzymes; antibiotics; antiviral agents; mitogens; cytokines; anti-inflammatory agents; immunotoxins; antibodies; and antigens. 
     
     
         37 . The brachytherapy seed of  claim 36 , wherein the drug is an anti-neoplastic agent. 
     
     
         38 . The brachytherapy seed of  claim 37 , wherein the anti-neoplastic agent is selected from the group consisting of paclitaxel, 5-fluorouracil, and cisplatin. 
     
     
         39 . The brachytherapy seed of  claim 36 , wherein the drug is a radiosensitizing agent. 
     
     
         40 . The brachytherapy seed of  claim 39 , wherein the radiosensitizing agent is selected from the group consisting of: 5-fluorouracil, etanidazole, tirapazamine, BUdR, and IUdR. 
     
     
         41 . The brachytherapy seed of  claim 25 , wherein the radiopaque marker is comprised of a substance selected from the group consisting of: platinum, iridium, rhenium, gold, tantalum, bismuth, indium, tungsten, silver, and radiopaque polymers. 
     
     
         42 . The brachytherapy seed of  claim 25 , wherein the radiopaque marker is biodegradable. 
     
     
         43 . The brachytherapy seed of  claim 25 , wherein the biocompatible component and the therapeutically active substance are formed into a plurality of microspheres. 
     
     
         44 . The brachytherapy seed of  claim 43 , wherein the microspheres are biodegradable. 
     
     
         45 . The brachytherapy seed of  claim 25 , wherein the seed further comprises magnetic elements. 
     
     
         46 . A method of making a brachytherapy seed for implantation into a subject comprising the steps of:
 (a) providing a biocompatible component, a therapeutically active component comprising a non-radioactive drug, and a radiopaque marker;   (b) physically associating the biocompatible component, the therapeutically active component, and the radiopaque marker to form a combination product; and   (c) forming the combination product into a seed having a size and shape suitable for passing through the bore of a needle having an interior diameter of less than about 2.7 millimeters (10 gauge).   
     
     
         47 . The method of  claim 46 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 1.4 millimeters (15 gauge). 
     
     
         48 . The method of  claim 46 , wherein said size and shape is suitable for passing through the bore of a needle having an interior diameter of less than about 0.84 millimeters (18 gauge). 
     
     
         49 . The method of  claim 46 , wherein the seed is shaped into a cylinder having a diameter of between about 0.8 to 3 millimeters and a length 4 to 10 millimeters. 
     
     
         50 . The method of  claim 49 , wherein the diameter is about 0.8 millimeters and the length is about 4.5 millimeters. 
     
     
         51 . The method of  claim 46 , wherein the biocompatible component is non-biodegradable. 
     
     
         52 . The method of  claim 46 , wherein the biocompatible component is biodegradable. 
     
     
         53 . The method of  claim 46 , wherein the biocompatible component is biodegradable and comprises a polymer selected from the group consisting of: poly(bis(p-carboxyphenoxy)propane anhydride); poly(bis(p-carboxy)methane anhydride); poly(D,L-lactic-coglycolic acid); poly(isobutylcyanoacrylate); a copolymer of poly-carboxyphenoxypropane and sebacic acid; open cell polylactic acid; a co-polymer of a poly-fatty acid dimer and sebacic acid; poly(carboxyphenoxy)hexane; poly-1,4-phenylene dipropionic acid; polyisophthalic acid; and polydodecanedioic acid,
 and the drug is selected from the group consisting of: anti-neoplastic agents and radiosensitizing agents. radioprotectants; hormones; enzymes; antibiotics; antiviral agents; mitogens; cytokines; anti-inflammatory agents; immunotoxins; antibodies; and antigens.   
     
     
         54 . The method of  claim 46 , wherein the radiopaque marker is comprised of a substance selected from the group consisting of platinum, iridium, rhenium, gold, tantalum, bismuth, indium, tungsten, silver, and radiopaque polymers. 
     
     
         55 . The method of  claim 46 , wherein the radiopaque marker is biodegradable. 
     
     
         56 . A method of making a brachytherapy seed for implantation into a subject comprising the steps of:
 (a) providing a biocompatible component, a therapeutically active component comprising a non-radioactive drug, and a sealed container housing a radioisotope; a radiopaque marker and   (b) physically associating the biocompatible component, the therapeutically active component, the container, and the radiopaque marker into a seed such wherein the biocompatible component and the therapeutically active component at least partially coat the container and the seed has a size and shape suitable for passing through the bore of a needle having an interior diameter of less than about 2.7 millimeters (10 gauge).   
     
     
         57 . The method of  claim 56 , wherein the biocompatible component is non-biodegradable. 
     
     
         58 . The method of  claim 56 , wherein the biocompatible component is biodegradable. 
     
     
         59 . The method of  claim 56 , where the radioisotope is selected from the group consisting of:  125 I and  103 Pd. 
     
     
         60 . The method of  claim 56 , wherein the biocompatible component and the therapeutically active component are formed into a plurality of microspheres.