Patent Publication Number: US-2005131267-A1

Title: System and method for delivering a therapeutic agent for bone disease

Description:
This application is a continuation-in-part of and claims priority to U.S. patent application Ser. No. 10/265,922, filed Oct. 7, 2002, which is a continuation-in-part of U.S. patent application Ser. No. 10/044,843 filed Jan. 11, 2002, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 10/054,736, filed Oct. 24, 2001, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 08/986,876 filed Dec. 8, 1997, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 08/911,805, filed Aug. 15, 1997, now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 08/871,114 filed Jun. 9, 1997, now issued U.S. Pat. No. 6,248,110, which is a continuation-in-part of U.S. patent application Ser. No. 08/659,678 filed Jun. 5, 1996, now issued U.S. Pat. No. 5,827,289, which is a continuation-in-part of U.S. patent application Ser. No. 08/485,394, filed Jun. 7, 1995, now abandoned, the disclosures of which are herein incorporated in their entirety by reference thereto. 
    
    
     TECHNICAL FIELD  
      This invention relates to therapy for bone disease. In particular, this invention relates to systems and methods for accessing bone to deposit a therapeutic agent.  
     BACKGROUND  
      When cancellous bone becomes diseased, for example, because of osteoporosis, avascular necrosis or cancer, it can no longer provide proper support to the surrounding cortical bone. The bone therefore becomes more prone to compression fracture or collapse.  
      Radiation therapy and chemotherapy are commonly used to treat cancerous conditions, such as spinal metastases. Radiation therapy can be administered in any of a number of ways, including external-beam radiation, stereotactic radiosurgery, and permanent or temporary interstitial brachytherapy.  
     SUMMARY  
      The methods and devices described allow for depositing a therapeutic agent directly to the interior volume of a skeletal support structure such as a vertebral body while minimizing exposure of surrounding tissue to radiation and to harmful side effects of the therapy. In one embodiment, a first expandable structure has a second expandable structure disposed within the first expandable structure. Furthermore, the first and second expandable structures are configured to expand a void in a skeletal support structure and to receive a radiation source between the first and second expandable structures.  
      The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
    
    
     DESCRIPTION OF DRAWINGS  
       FIG. 1  shows an apparatus including a first elongated member and a second elongated member having an expandable structure.  
       FIG. 2A  shows an expandable structure connected to a second elongated member in an unexpanded configuration.  
       FIG. 2B  shows an expandable structure connected to a second elongated member in an expanded configuration.  
       FIG. 2C  is cross-sectional end view of the expandable structure of  FIG. 2B .  
       FIG. 2D  is a cross-sectional end view of the second elongated member of  FIG. 2A .  
       FIG. 3  shows an apparatus including a first elongated member and a second elongated member having an expandable structure, disposed within a vertebral body.  
       FIG. 4A  shows an expandable structure including a primary lumen and a number of secondary lumens, in an unexpanded configuration.  
       FIG. 4B  shows an expandable structure of  FIG. 4A  in an expanded configuration.  
       FIG. 4C  is cross-sectional end view of the expandable structure of  FIG. 4B  in an expanded configuration.  
       FIG. 4D  is a cross-sectional end view of the second elongated member of  FIG. 4A . 
    
    
      Like reference symbols in the various drawings indicate like elements.  
     DETAILED DESCRIPTION  
       FIG. 1  shows an apparatus  100  for providing a radiation source to the interior of a skeletal support structure. The apparatus  100  includes a first elongated member  101  having a lumen  104 , wherein the first elongated member  101  is configured to provide non-axial access to the interior of the skeletal support structure. In one implementation, the first elongated member  101  can be configured, for example, as a cannula, catheter, needle, trocar or other suitable access device. The apparatus  100  includes a second elongated member  102  configured to transport a therapeutic agent through the lumen  104  of the first elongated member  101  to the interior of the skeletal support structure. Finally, the apparatus  100  includes an expandable structure  103  configured for insertion into a skeletal support structure, wherein the expandable structure  103  is configured to create/expand a void within the skeletal support structure.  
      The therapeutic agent transported to the interior of the skeletal support structure can include but is not limited to, for example a chemotherapeutic agent, a radiation source or combinations thereof.  
      The skeletal support structure accessed using the apparatus  100  can include, but is not limited to, for example, bone, cartilage and ossified derivatives thereof, membrane bone and cartilage bone. As shown in  FIG. 3 , in one implementation the first elongated member  101  facilitates access to a skeletal support structure consisting of a vertebral body  301 . Particularly, as shown in  FIG. 3 , the interior volume  304 , typically containing cancellous bone  305 , is accessed via the first elongated member  101  through the pedicle  303  of the vertebral body  301 . Access to the interior of the vertebral body  301  can be accomplished via the side walls of the vertebral body  301 , for example, using an extrapedicular, postero-lateral, lateral, or anterior approach; or also via the vertebral body  301  endplates.  
      As shown in FIGS.  1 ,  2 A- 2 C and  3 , in one implementation the second elongated member  102  has a distal end that includes an expandable structure  103  configured to create a void  302  within the skeletal support structure (e.g., see void  302  in  FIG. 3 ). As used herein, “expandable” refers to a property of the structure that includes elastic, non-elastic, and partially elastic/non-elastic expansion. The expandable structure can be made from a deformable plastic or metal material. As used herein, “create a void” is meant to include both expanding an existing void in a skeletal support structure in addition to expanding the interior of a skeletal support structure to produce a void. It is contemplated that a skeletal support structure accessed with the apparatus  100  can comprise a void prior to being accessed or upon being accessed. It is further contemplated that such a prior existing or contemporaneously formed void can be further expanded using the above-described expandable structure  103 .  
      As shown in FIGS.  2 A-D, the expandable structure  103  is coupled to the second elongated member  102  and can be configured to deliver a radiation dose to the interior of the skeletal support structure. In the implementation shown, the expandable structure  103  is comprised of a first expandable structure  200  and a second expandable structure  201 . The first and second expandable structures  200  and  201  are configured to define a primary lumen  202  and a secondary lumen  203  (see FIGS.  2 A-C). Examples of suitable primary and secondary lumens  202  and  203  include but are not limited to, inner open spaces or cavities within a tube, sleeve, pocket, pouch, sac, bag, or vessel. In one implementation, the primary and secondary lumens  202  and  203  extend into and span substantially the length of the second elongated member  102 . A radiation source can be received between the first and second expandable structures  200  and  201  in the secondary lumen  203 . Expansion of the expandable structure  103  can be controlled by the addition of a substance (e.g., a fluid) to, for example, the primary lumen  202 .  
      In one embodiment, as shown in  FIGS. 2B and 2C , the first expandable structure  200  and second expandable structure  201  are configured to achieve a correlated expanded state. As used herein, “correlated expanded state” is meant to describe an expansion of the first and second expandable structures  200  and  201 , synchronously or asynchronously, at a same or different rates or any suitable manner to achieve a fixed relationship or a variable one depending on the elasticity or other properties of the expandable structures  200  and  201 . For example, the first expandable structure  200  can be expanded to a first size while coincidentally the second expandable structure  201  can be expanded to substantially the same first size. Alternatively, the first expandable structure  200  can be expanded to a first size while coincidentally the second expandable structure  201  can be expanded to a second size. After expansion, the first and second expandable structures  200  and  201  are configured to unexpand. The unexpanded configuration can facilitate, for example, removal of part or all of the apparatus  100  from a skeletal support structure.  
      In one implementation, the second elongated member  102  is configured at the distal end to be remotely visualized (e.g., using fluoroscopy, X-ray, MRI, CT scan, or computer-aided imaging) while the distal end is inside the interior of the skeletal support structure. Such a configuration can include suitable marking means for remote visualization disposed substantially near the distal end of the second elongated member  102  (not shown). For example, such a configuration can be accomplished using one or more radiopaque marker bands. In another example, the expandable structure  103  can be comprised of one or more radiopacifer. Examples of radiopacifiers include but are not limited to, iodine (such as CONRAY® available from Mallinckrodt), gadoliminum, tungsten, tantalum, barium, strontium. It is contemplated that a radiopacifier or a radiopaque substance can be disposed within the primary lumen  202 , and/or the secondary lumen  203  of the expandable structure  103 . Alternatively, the first expandable structure  200  and/or the second expandable structure  201  can be co-manufactured with a radiopacifier, or could be coated on the inside or outside of the expandable structure  103 .  
      In another implementation, the first elongated member  101  is further comprised of a means for penetrating a skeletal support structure (not shown). As used herein, “means for penetrating a skeletal support structure” include, but are not limited to, a stylet, drill, trocar, needle assembly, catheter and any other practicable device for penetrating a skeletal support structure. The means for penetrating a skeletal support structure can be coupled to the distal end of the first elongated member  101 , or configured for use in conjunction with the elongated member  101 . The means for penetrating a skeletal support structure can also be coupled to the second elongated member  102 .  
      In one implementation, the radiation source can be positioned at a predetermined location (e.g., in relation to the skeletal support structure). Where step-wise positioning is indicated, the predetermined location can be a series of dwell positions (discussed below) substantially near or within a skeletal support structure. The positioning of the radiation source can be controlled by the configuration of the first and second elongated members  101  and  102 . The relevant configuration of the first and second elongated members  101  and  102  can include but is not limited to, for example, indexes or markings that communicate the positional relationship between the first and second elongated members  101  and  102  (not shown). Positioning of the radiation source can be aided by the use of CT scan to determine the measurement of the skeletal support structure and to calculate the distance to place in the desired position. Positioning the radiation source within the skeletal support structure can also be controlled based on the expansion of the expandable structure  103 . For example, the relative amount of expansion of the expandable structure can provide positioning of the radiation source deployed within the expandable structure  103  at a number of predetermined locations within or near the skeletal support structure (e.g., within the interior volume  304  of a vertebral body  301 ).  
      In one implementation, the radiation source is configured to provide a dose of radiation substantially localized within the interior of the skeletal support structure. In particular, the form and substance of the radiation source, in conjunction with the configuration and deployment of the second elongated member  102 , can be adjusted to provide a desired localized dose. Such a dose is calculable. For example, a dosimetry plan can be used to calculate how long the radiation source should spend (dwell time) in specified localized positions (dwell position) within the skeletal support structure.  
      In a particular implementation, the radiation source is received within the void  302  using an afterloader (not shown). The afterloader can be coupled to a lumen of the second elongated member  102  of the apparatus  100  for introduction of a radiation source within the lumen.  
      In one embodiment, the radiation source is a radionuclide. The radionuclide can be in the form of a liquid, seed, needle, pellet, particle, microsphere, or any other suitable form of radionuclide for radiation treatment. The radionuclide can be comprised of Au-198, Co-60, Cs-137, I-125, I-135, Ir-192, P-32, Pd-103, Ra-226, Rh-106, Ru-106, Sr-90, Y-90 or any other isotope suitable for radiation treatment, and can be liquid, solid or generated in situ by electronic brachytherapy (available from Xoft, Inc.)  
      In one implementation, the apparatus  100  is further comprised of a radiation shield configured to shield the radiation source (not shown). The shield can be configured to contain emissions from the radiation source until release of the emissions is desired, for example, to provide dose to local bone. In one embodiment, the shield can be configured to enclose the second elongated member  102  and/or the expandable structure  103  coupled thereto (not shown). In another embodiment, the shield can be comprised of a metal mesh, which is inserted into the interior of the skeletal support structure after expansion of the expandable structure  103 . In yet another embodiment, the shield can be incorporated into the first expandable structure  200  and/or second expandable structure  201 .  
      Referring to  FIGS. 1 and 3 , a method of using the apparatus  100  described above comprises: inserting non-axially, into an interior of a skeletal support structure, a first elongated member  101  having a lumen  104  that defines an access path into the interior of the skeletal support structure; inserting, into the lumen  104 , a second elongated member  102  configured to transport a radiation source to the interior of the skeletal support structure; and transporting the radiation source through the lumen  104  into the interior of the skeletal support structure.  
      In one implementation, the method of using the apparatus  100  further comprises expanding at least a portion of the second elongated member  102  to create a void  302  in the interior of the skeletal support structure. Expanding the second elongated member  102  to create a void  302  can optionally be executed before or after transporting the radiation source through the lumen.  
      In another implementation, the method of using the apparatus  100  further comprises depositing a supportive material in the void  302 . The supportive material can be bone cement (e.g., polymethyl methacrylate (PMMA), ceramics), human bone graft (autograft and allograft), synthetic derived bone substitutes such as calcium sulfate, calcium phosphate and hydroxyapatite. Additionally, in another implementation, the supportive material can include a chemotherapeutic agent.  
      In one implementation, the method step of transporting the radiation source further comprises placing the radiation source at one or more dwell positions. Furthermore, the method can include determining multiple dwell positions to provide a dose of radiation substantially localized within the interior of the skeletal support structure. Determining dwell positions includes but is not limited to computer software determination of dwell positions.  
      In another implementation, the method step of inserting the first elongated device  101  comprises inserting the first elongated device  101  into an interior volume  304  of a vertebral body  301  through a pedicle  303  of a vertebral body  301  (see  FIG. 3 ). In another implementation, two or more first elongated devices  101  are inserted through one or more pedicles  303  of a vertebral body  301 . Alternatively, the step of inserting the first elongated device  101  can comprise inserting one or more of the first elongated device  101  into an interior volume  304  of a vertebral body  301  through the side walls of the vertebral body  301 . For example, the first elongated device  101  can be inserted by way of an extrapedicular, postero-lateral, lateral, or anterior approach; or alternatively via the vertebral body  301  endplates. In another implementation, the method step of inserting the first elongated device  101  comprises inserting the first elongated device  101  into a skeletal support structure including bone, cartilage and ossified derivatives thereof, membrane bone and cartilage bone.  
      As described above, an apparatus  100  is provided for use within the interior of a skeletal support structure that includes an expandable structure that can be comprised of at least one lumen configured to contain a radiation source. As shown in  FIG. 4A -D, the apparatus  100  can comprise an expandable structure  103  configured for insertion into a skeletal support structure and optionally configured to be coupled to an elongated member such as the second elongated member  102  described above (see  FIGS. 1, 2A ,  2 B and  2 D).  
      The expandable structure  103  can include a first layer and a second layer. The first and second layers can be configured to receive a radiation source between the first layer and the second layer. In one implementation, as shown in FIGS.  4 A-D, the expandable structure  103  includes a primary lumen  202 , and at least one secondary lumen  203 . The primary and secondary lumens  202  and  203  are configured to be in fluid communication with a lumen in the second elongated member  102 . In the implementation shown in FIGS.  4 A-D, the primary and secondary lumens  202  and  203  extend into and substantially span the length of the second elongated member  102 .  
      In another implementation, the first and second expandable structures  200  and  201  are comprised of a material having properties or characteristics including compliant or non-compliant and combinations thereof. As used herein, “compliant” includes the properties of flexibility in an elastic, expandable or bendable way. Additionally, as used herein, “non-compliant” includes a rigid quality although, depending on the context, may not imply complete rigidity. By varying the incorporation of such material when manufacturing the first and second expandable structures  200  and  201 , different sizes, shapes and consistencies of the un-expanded and expanded first and second expandable structures  200  and  201  can be achieved.  
      The expandable structure  103  can be configured for insertion into a skeletal structure in an unexpanded configuration. Insertion of the unexpanded expandable structure  103  into the skeletal support structure can create a void  302  within the skeletal support structure. The expandable structure  103  can further be configured to create or expand a void within a skeletal support structure upon expansion of the expandable structure  103 . As shown in  FIGS. 3, 4A  and  4 B, in one implementation, the expandable structure  103  is configured for insertion into a void (e.g., void  302 ) in an unexpanded configuration (see  FIG. 4A ), expanded into the void to an expanded configuration (see  FIG. 4B ), and unexpanded after expansion. A void  302  in the interior volume  304  of a vertebral body  301  can be increased by the expansion of the first and second expandable structures  200  and  201  within the interior volume  304 . As shown in  FIG. 3 , the void  302  is provided when one or more of the first and second expandable structures  200  and  201  are expanded, which result from the compaction of cancellous bone  305 .  
      In one implementation, the expandable structure  103  is comprised of an expandable material having an interior lumen, the expandable material being configured to expand to a first shape, and to reversibly expand to a second shape. As shown in FIGS.  2 A-D, the expandable structure  103  of the apparatus  100  can comprise a first expandable structure  200 , and a second expandable structure  201  disposed within the first expandable structure  200 . Additionally, the first and second expandable structures  200  and  201  include interior and exterior walls. A substance (e.g., a fluid) can be introduced into the interior lumen (shown in FIGS.  2 A-C as primary lumen  202 ), where the fluid can be caused to force against the interior wall of the second expandable structure  201  to provide expansion of the expandable structure  103  including the first and second expandable structures  200  and  201  (not shown). As shown in FIGS.  2 A-C, there is a secondary lumen  203  disposed between the first and second expandable structures  200  and  201 . In one implementation, the secondary lumen  203  is configured to receive a substance (e.g., a fluid). Particularly, the substance received in the secondary lumen  203  can be a radiation source.  
      In one implementation, the first and second expandable structures  200  and  201  are configured for optional removal of either the first, second or both expandable structures  200  and  201  from the distal end of the second elongated member  102  of the apparatus  100  (not shown). For example, the first expandable structure  200  can be configured for removal from the apparatus  100 , wherein upon removal, the second expandable structure  201  remains attached to the second elongated member  102  of the apparatus  100 . Alternatively, the second expandable structure  201  can be configured for removal from the apparatus  100 , wherein upon removal of the second expandable structure  201 , the first expandable structure  200  is left attached to the second elongated member  102  of the apparatus  100 . In one implementation, the configuration of the expandable structure  103  forms a tube, sleeve, pocket, pouch, sac, bag, vessel or other suitable enclosed space.  
      In another implementation, the expandable structure  103  includes an expandable geometry configured to reversibly expand to a desired shape (not shown). Examples of such expandable geometries include, but are not limited to, coiled wires, various types of springs, and self-expanding stents or scaffolds. In one implementation, the apparatus  100  further comprises an insertion sleeve configured to substantially surround the expandable structure  103  (not shown). The insertion sleeve can be used to protect the expandable structure during placement and removal from the interior of the skeletal support structure. The insertion sleeve can also protect the surrounding tissues during removal of diseased tissue or instruments, which have come into contact with diseased tissue. The insertion sleeve can help prevent “seeding” of the diseased tissue to other tissues in the access pathway.  
      As shown in  FIGS. 4A and 4B , the expandable structure  103  is comprised of a primary lumen  202  and a secondary lumen  203 . The primary lumen  202  can be configured for expanding the expandable structure  103  and the secondary lumen  203  can be configured for containing the radiation source (see  FIGS. 4A and 4B ). Alternatively, in another implementation, the primary lumen  202  can be configured for containing the radiation source while the secondary lumen  203  is configured for expanding the expandable structure  103 .  
      As shown in  FIGS. 4A and 4B , at least one secondary lumen  203  is disposed substantially parallel to the long-axis of the second elongated member  102 . Additionally, the at least one secondary lumen  203  is disposed circumferentially about the expandable structure  103  (see  FIGS. 4A and 4B ). Any of a number of configurations for disposing the at least one secondary lumen  203  in relation to the second elongated member  102  and the expandable structure  103  can be used. For example the number and orientation of the secondary lumens (i.e., the at least one secondary lumen  203 ) can be varied to optimize containing and transporting the radiation source.  
      In one implementation, the expandable structure  103  is comprised of one or more lumens having been co-manufactured with the radiation source. For example, the at least one secondary lumen  203  can be co-manufactured with the radiation source. Alternatively, the primary lumen  202  can be co-manufactured with the radiation source.  
      As shown in FIGS.  4 A-D, in one implementation, the at least one lumen  203  of the expandable structure  103  comprises a catheter  400  disposed within and having an opening  402  substantially near the distal end of the expandable structure  103 . The opening  402  may accommodate the passage of a guidewire or stiffening stylet. The catheter  400  comprises a catheter lumen  401  and can extend into and substantially span the length of the second elongated member  102  (see FIGS.  4 A-D). In another implementation, the at least one lumen  203  of the expandable structure  103  does not include an opening or exit near the distal end of the expandable structure  103 .  
      A method of using the above described expandable structure  103  comprises inserting the expandable structure  103  into a skeletal support structure, wherein the expandable structure  103  comprises at least one lumen configured to receive a radiation source; expanding the expandable structure  103 ; and transporting the radiation source through the at least one lumen into the skeletal support structure. In another implementation, the method further comprises depositing a supportive material in the skeletal support structure. The supportive material can be bone cement (e.g., polymethyl methacrylate (PMMA), ceramics), human bone graft (autograft and allograft), synthetic derived bone substitutes such as calcium sulfate, calcium phosphate and hydroxyapatite. Additionally, in another implementation, the supportive material can include a chemotherapeutic agent or a radioactive agent.  
      In one implementation, the apparatus  100 , including the expandable structure  103 , is configured to provide minimally invasive insertion into a skeletal support structure. For example, as shown in  FIG. 3 , the apparatus  100  comprising first and second elongated members  101  and  102  includes a minimally invasive configuration for deployment within the interior volume  304  of a vertebral body  301 . The configuration is minimally invasive since only a small access through the skin and muscle layers to a desired part of the vertebral body  301  (e.g., through a pedicle  303  as shown in  FIG. 3 ) is required to introduce the apparatus  100  within the interior volume  304 . Alternatively, the minimally invasive approach can be applied to the side walls of the vertebral body  301 . For example, a desired part of the vertebral body  301  can be accessed through an extrapedicular, postero-lateral, lateral, or anterior approach; or alternatively via the vertebral body  301  endplates. Other skeletal support structures the minimally invasive insertion approach can be applied to include but are not limited to, bone, cartilage and ossified derivatives thereof, membrane bone and cartilage bone.  
      A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.