Absorbable brachytherapy and chemotherapy delivery devices and methods

Abstract

Combination radiation delivery and chemotherapy devices comprise bioabsorbable structures with radionuclides and chemotherapeutic agents immobilized on said structures. The bioabsorbable structures have a predefined persistence period which is usually substantially greater than the half-life of the radionuclides, thus assuring that the radionuclides remain localized and sequestered at a desired target site while significant radioactivity remains. The radiation delivery and chemotherapy devices are suitable for a wide variety of medical purposes, being particularly suitable for the treatment of solid tumors by injection or open surgical introduction of the devices at a target site. Kits comprising the devices together with instructions for use are also provided.

What is claimed is:  
     
         1 . A radiation delivery device, said device comprising: 
 a bioabsorbable structure having a predefined persistence period when implanted in a patient; and    a radionuclide having a known half-life immobilized on said structure, where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide so that loss of radioactivity from the target site is minimized.    
     
     
         2 . A radiation delivery device as in  claim 1 , wherein the bioabsorbable structure has a persistence period in the range from 2 days to 90 days.  
     
     
         3 . A radiation delivery device as in  claim 1  or  2 , wherein the radionuclide has a half-life of 60 days or less.  
     
     
         4 . A radiation device as in claims  1  or  2 , wherein the biodegradable structure is composed of a biological polymer.  
     
     
         5 . A radiation device as in claims  1  or  4 , wherein the biodegradable structure has a drug incorporated into said structure.  
     
     
         6 . A radiation device as in  claim 5 , wherein the drug incorporated into the biodegradable structure is substantially released within two half-lives of the radionuclide.  
     
     
         7 . A radiation device as in  claim 5 , wherein the drug incorporated into the biodegradable structure is a chemotherapeutic agent.  
     
     
         8 . A radiation delivery device as in  claim 1  or  4 , wherein the biodegradable structure is formed as an implantable macrostructure comprising a continuous core structure with a minimum width of at least 1 mm.  
     
     
         9 . A radiation delivery device as in  claim 1  or  4 , wherein the biodegradable structure is formed as an implantable microstructure comprising core particles having an average width below 1 mm.  
     
     
         10 . A radiation delivery device as in  claim 1 , wherein the radionuclide is selected from the group consisting of Cu-162, Cu-64, Cu-67, Ru-97, Rh-105, Pd-109, Sm-153, Ho-166, Re-186, Re-188, Au-198, Au-199, Pb-203, Pb-211, Bi-212, 1-125, I-131, Y-90, Pd-103, Ir-192 and P-32.  
     
     
         11 . A radiation delivery device as in  claim 1 , wherein the radionuclide is covalently bound to a preformed surface on the bioabsorbable structure.  
     
     
         12 . A radiation delivery device as in  claim 11 , wherein the radionuclide is covalently bound through a linker which is bound to the surface.  
     
     
         13 . A radiation delivery device as in  claim 1 , wherein the radionuclide is chelated, adsorbed, precipitated, or complexed to a preformed surface on the bioabsorbable surface.  
     
     
         14 . A radiation delivery device as in  claim 1 , wherein the radionuclide is suspended within a substance or mixed with a substance which undergoes gelation, solation, or solidification upon introduction into the body.  
     
     
         15 . A method for localized delivery of radioactivity to a target site in tissue, said method comprising implanting a radiation delivery device according to  claim 1  at said target site.  
     
     
         16 . A method for localized delivery of radioactivity and drugs to a target site in tissue, said method comprising implanting a radiation delivery device according to  claim 5  at said target site.  
     
     
         17 . A method as in claims  15  or  16 , wherein the radiation delivery device comprises an injectable matrix and implanting comprising injecting the matrix to said site.  
     
     
         18 . A method as in  claim 15  or  16 , wherein implanting comprises surgically exposing the target site and placing the device at the surgically exposed site.  
     
     
         19 . A method for preparing a treatment delivery device, said method comprising: 
 providing a bioabsorbable structure having a predefined persistence period and a surface wherein at least a portion of the surface has been coated with a substrate material;    providing a radioactive material including a bonding constituent which can be bonded to the substrate material and a radioactive isotope, where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide;    determining the specific activity of the radioactive material; and    bonding an amount of the radioactive material to the substrate material on the device selected to provide a predetermined radioactive dosage.    
     
     
         20 . A method as in  claim 19 , wherein the predetermined dosage is in the range from 20 gray to 200 gray.  
     
     
         21 . A method as in  claim 19 , wherein the bioabsorbable structure has a persistence period in the range from 2 days to 90 days.  
     
     
         22 . A method as in  claim 19  or  21 , wherein the radionuclide has a half-life of 60 days or less.  
     
     
         23 . A method as in  claim 19 , wherein the bonding step comprises covalently bonding the radioactive material to the substrate material.  
     
     
         24 . A method as in  claim 19 , wherein the biodegradable structure is composed of a biological polymer.  
     
     
         25 . A method as in  claim 19  or  24 , wherein the biodegradable structure is formed as an implantable macrostructure comprising a continuous core structure with a minimum width of at least 1 mm.  
     
     
         26 . A method as in  claim 19  or  24 , wherein the biodegradable structure is formed as an implantable microstructure comprising core particles having an average width below 1 mm.  
     
     
         27 . A method as in  claim 19 , wherein the substrate material is selected from the group consisting of siloxanes and bifunctional chelating agents.  
     
     
         28 . A method as in  claim 19 , wherein the radioactive material comprises a radionuclide and a bonding component.  
     
     
         29 . A method as in  claim 19 , wherein the bioabsorbable structure has dispersed therein a drug.  
     
     
         30 . A method as in  claim 19 , further comprising the steps of: 
 providing a sustained release drug material which can be bonded to the substrate material, where the persistence period of the bioabsorbable structure is substantially longer than the period required to release substantially release the drug; and    bonding an effective amount of the sustained release drug material to the substrate material on the device.    
     
     
         31 . A method as in claims  29  or  30 , wherein the drug is a chemotherapeutic drug.  
     
     
         32 . A kit comprising: 
 a radiation delivery device according to  claim 1;  and    instructions describing a method for implanting the device in tissue.    
     
     
         33 . A kit as in  claim 32 , further comprising a package which contains the device and the instructions.  
     
     
         34 . A kit as in  claim 33 , wherein the instructions further set forth a method for coating the radiation delivery device with a radioactive material prior to implantation.