WO2000013740A2

WO2000013740A2 - Radioactive sleeve

Info

Publication number: WO2000013740A2
Application number: PCT/US1999/020335
Authority: WO
Inventors: Charles L. Brown; Nicholas Chronos
Original assignee: Global Vascular Concepts, Inc.
Priority date: 1998-09-03
Filing date: 1999-09-03
Publication date: 2000-03-16
Also published as: AU1090400A; WO2000013740A3

Abstract

The present invention provides a device for administering radiation to a bodily vesicle, comprising a radiation-emitting sleeve having a generally tubular structure with at least one end adapted for communicating with a distal end of a catheter, wherein the sleeve when in communication with the catheter is expandable from a first positioning diameter to a second larger radiation delivery diameter, and is further retractable back to the first positioning diameter.

Description

RADIOACTIVE SLEEVE

Field of the Invention

The present invention relates to the field of catheter and device-assisted radiation therapy for the prevention of restenosis.

Background of the Invention The response to tissue injury remains one of the major limitations of percutaneous angioplasty procedures and stent placement. The response of the vessel wall to the balloon barotrauma, stent placement, placement of a vascular graft (arterial, or arteriovenous graft e.g., dialysis graft) remains a significant limitation of these procedures. This response is a complex interaction of inflammation, smooth muscle cell migration, proliferation and myofibroblast transformation that occurs as soon as the barotrauma/trauma occurs and can in a varying number of patients, limit the procedures' success. Angioplasty procedures generally involve the introduction of a small balloon catheter into the femoral artery in a patient's leg and, with the help of a guide wire, the catheter is passed by remote manipulation under fluoroscopy into the heart. The balloon can then be positioned in a region of a coronary artery that has become constricted due to atherosclerosis and by inflating and deflating the balloon several times the bore of the diseased artery is mechanically widened until a satisfactory blood flow through the vessel has been restored. If the artery is severely damaged by disease, and perhaps hardened by calcium deposition, this balloon inflation may also cause some degree of additional injury with local de-endothelialisation and exposure of underlying extracellular matrix components such as collagen and elastin. In a few patients excessive recruitment of platelets and fibrinogen can then result in an acute thrombotic occlusion. This is now less common, however, with the routine use of heparin and aspirin cover during the angioplasty procedure.

Generally, angioplasty procedures produce excellent results obviating the need for bypass surgery, but in about 30 - 40% of patients, an ostensibly successful initial dilatation of the artery may be followed by a renarrowing of the vessel (restenosis) some 3 to 9 months later. If this restenosis is severe, these patients may require a second angioplasty procedure, often with implantation of a stent to act as a scaffold in the vessel. In other cases arterial reconstruction under by-pass surgery, which is a higher risk procedure, may be required. With more than 800,000 PTCA procedures now performed world- wide annually, the socio-economic implication of this 30 - 40% restenosis rate has become a matter of serious concern to interventional cardiologists. The pathophysiology of this late restenosis is complex, and involves a wide range of cellular and molecular responses, many of which are not yet fully understood. Although a number of putative targets for drug interference have been identified, more than 50 clinical trials (some large and multi-center) with a wide range of different drugs have failed to reveal a satisfactory pharmacotherapeutic approach to reducing the incidence of restenosis. One problem is that for some of the potentially useful drugs, it is not possible by systemic administration to get a therapeutically effective level of the drug in the vessel wall tissue without significantly affecting non-target tissues elsewhere.

Endovascular radiation therapy for the prevention of restenosis has become a popular mode of treatment under investigation in cardiovascular medicine. Industry is quickly developing an array of delivery systems to facilitate safe delivery and removal of active isotopes delivered endoluminally to the patient, both in the vascular spaces and in other anatomical locations.

Current delivery systems mostly utilize concepts based on delivery and retraction of a source back and forth through a catheter lumen. These sources can be in the form of a wire, liquid or gas, or pellets (seeds) which are transferred through a catheter lumen to the intended treatment site. After the appropriate dwell time they are withdrawn from the body. Current systems are all dependent on out of body storage of the radioisotope source and the use of a delivery device which itself can frequently be cumbersome. These delivery devices are not always dependable in their delivery and dosimetry of isotopes.

Accordingly, what is needed are improved devices and methods for delivering radiation-emitting agents to specific locations within the body. These methods would deliver the radiological agents to a site in effective amounts, and thus reduce or prevent the occurrence of restenosis. Summary of the Invention

The present invention provides for the use of radiation- emitting agents to prevent and inhibit an undesirable response to vessel wall injury, including restenosis, neointima or cancer. The present invention provides the local delivery of radioactive materials to bodily vesicles via a catheter in an expandable and retractable sleeve form. The present invention is particularly applicable to the local delivery of radiation-emitting agents during and after interventional cardiology procedures such as angioplasty and stent implantation.

Accordingly, it is an object of the present invention to provide devices and methods for enhancing the local delivery of radioactive materials.

It is another object of the present invention to provide methods for the localized treatment of undesirable cellular growth, such as angiogenesis or cancer.

It is another object of the present invention to provide methods to deliver radiation treatment agents to specific tissues in a proper dosimetry. These and other objects, features and advantages of the present mvention will become apparent after a review of the following detailed description of the disclosed embodiments and the appended claims.

Detailed Description of the Invention

The present invention provides the improved use of radiation-emitting materials via an expandable and retractable sleeve attached to conventional or specially adapted catheter delivery devices. This therapeutic approach is aimed at reducing cellular growth, such as may be due to angiogenesis or cancer, that occurs locally at the site of injury or disease, thus potentially reducing or preventing undesirable responses to injury or disease, such as narrowing, renarrowing or restenosis of veins and arteries.

The present invention relates to the inhibition of undesirable cellular growth and angiogenesis with a consequent reduction in the delivery and release of 0₂ and substrates of metabolism within the vessel wall and a reduction in the removal of the waste products of metabolism. The invention renders the microenvironment unfavorable for migration and proliferation of smooth muscle cells, inflammatory cells and other cells involved in the undesirable response to injury.

The present invention provides a device for administering radiation to a bodily vesicle, comprising a radiation-emitting sleeve having a generally tubular structure with at least one end adapted for communicating with a distal end of a catheter, wherein the sleeve when in communication with the catheter is expandable from a first positioning diameter to a second larger radiation administration diameter, and is further retractable back to the first positioning diameter.

The invention provides that the sleeve is sized for delivery within a bodily vesicle. For example, the sleeve can have a first positioning diameter of approximately 2 mm and a second administration diameter of approximately 8 mm. Alternatively, in another embodiment for larger vesicles, the sleeve can have a first positioning diameter of approximately 8 mm and a second administration diameter of approximately 14 mm. The length of the sleeve can vary, and can preferably be in the range of 5 to 50 mm.

Therefore, the invention provides that the radiation-emitting agents are incorporated into a sleeve having a generally tubular form. The sleeve can be shaped to receive an expandable portion of a catheter in the proximal end thereof. The sleeve can be open or closed at the opposite, or distal, end. The sleeve is expandable from a first placement position to a second radiation delivery position, and importantly is capable of contracting back to the first position for withdrawal from the vesicle. Therefore, the sleeve can be constructed from a visco-elastic material, such that it can be expanded when placed over an appropriate delivery catheter, e.g. an angioplasty ballon, and then retract by itself when the delivery catheter is deflated. Alternatively, the sleeve can be mechanically expandable and retractable by action of its communication with the attached catheter.

The present invention provides that radiation-emitting agents can be incorporated into polymers or co-polymers and shaped into sleeve forms, which are capable of expansion and retraction when delivered to the site of interest via an expandable catheter. In addition, the radiation-emitting agents can be incorporated into metallic sleeve structures, which are capable of expansion and retraction when delivered to the site of interest via a catheter. The sleeve can be made radioactive by having the isotope embedded in the sleeve material, or the sleeve can have properties which allow onsite irradiation of the sleeve itself, done specifically at the time of use.

A number of different polymeric materials and methods of fabrication may be used to form the sleeves used in the present invention. Examples of suitable polymer materials or combinations include, but are not limited to, biocompatible and/or biodegradable polymers such as poly(lactides), polyglycolides, polyanhydrides, polyorthoesters, polyactals, polydihydropyrans, polycyanoacrylates and copolymers of these and polyethylene glycol.

According to the present invention, the radiation-emitting sources include, but are not limited to, those emitting beta, gamma, and X-radiation. It should be understood that any form or radiation that can be used therapeutically can be used in the present invention. The amount of radiation-emitting material to be applied is highly variable depending upon the type and efficacy of material selected, the extent of the injury, the condition and responsiveness of the patient, the aggressiveness of the physician's regimen, and so forth. However, the determination of a cellular growth, angiogenesis or restenosis inhibiting effective amount of a radiation-emitting agent in any particular circumstances is within the routine skill of artisans in view of the present disclosure. Further, an appropriate predetermined residence time in the vessel at the site of treatment for delivery of the radiation therapy will be highly variable, however, approximately 2 to 10 minutes is preferred.

The invention provides methods of administering radiation therapy to a bodily vesicle, comprising inserting into the vesicle the radiation-emitting sleeve having a tubular structure and comprising a proximal end in communication with the distal end of a catheter, wherein the sleeve when in communication with the catheter is expandable from a first positioning diameter to a second larger radiation administration diameter, and is further retractable back to the first positioning diameter. The methods further comprise positioning the sleeve at a desired site for radiation therapy within the vesicle; expanding the sleeve to the second radiation delivery diameter; delivering the radiation therapy for a predetermined residence time; retracting the sleeve to the first positioning diameter; and withdrawing the sleeve from the bodily vesicle.

One particularly advantageous property of this invention is that it answers the problem of eccentric dosing of radiation to the vessel wall. Since delivery of the radiation-emitting agent in the sleeve is circumferential, there is no centering issue or disproportionate dosing in the vessel or cavity. This invention also addresses problems related to beta penetration limits, which are problematic within the larger vessels and using conventional radioactive pellets. As the isotope is delivered at the vessel wall by the present invention, there is not a diameter limit for penetrance, as is the case with conventional centered beta delivery systems. This invention can be used both for small (approximately 2 to 4 mm) coronary vessels, as well as larger (approximately 4 to 14 mm) aorto/iliac/femoral vessels.

The present invention includes the use of radiation-emitting agents in an expandable and retractable sleeve for the treatment of the following classes of injuries and diseases including, but not limited to, cancer, atherosclerosis, cardiac transplant vasculopathy, coronary restenosis following coronary intervention including, but not limited to, balloon angioplasty, stent placement, rotablator, and other endoluminal procedures; carotid endarterectomy, stenting and angioplasty, peripheral artery and renal artery angioplasty and stent placement, dialysis graft stenosis (venous or arterial end), and large and small bore graft anastomosis neointima. Additionally, the present invention includes the use of radiation-emitting agents endoluminally in conditions of benign hypertrophy or tissue including benign prostatic hypertrophy, ingrowth of benign liver tissue into stents placed during the TIPS procedure. The sleeve of the present invention can also be used to treat undesirable cellular growth, such as tumors, encroaching into the lumen of tubes in the body such as the biliary system, the prostate, the fallopian tubes and ovaries, or the esophagus, for example.

In particular, the present invention relates to the use of radiation-emitting agents in catheter-based devices which answers many problems surrounding radiation delivery systems. It specifically addresses improvement in storage of the radioactive source. It facilitates easy delivery of the source to the treatment site, and storage of the source outside the body with simple removal of the source from the delivery catheter. In addition, the invention provides good vessel or cavity wall penetration with safer, contained use of isotopes, and also provides an easily disposable device once radiation delivery is complete.

The sleeve of the present invention has a mechanism which allows the user to removably attach the sleeve in expandable and retractable communication with a conventional or specially adapted catheter at the time of delivery, and have a radiation source attached to the delivery catheter, ready for use. Such an attachment can be by a variety of well-known means, including one or more tethers, clips, flanges, fasteners or reciprocating threaded portions affixing the sleeve in position on the catheter at one or more points, with the proviso that the attachment does not prevent expansion and retraction of the sleeve. Alternatively, the sleeve can also be woven into the distal braids of an expandable wire catheter.

The catheter delivery system can be a balloon design with locking attachments for the sleeve, or the catheter delivery system can be an expandable mesh or wire braid design. Any catheter design having an expandable distal end will suffice. Once the catheter has been used and has delivered the pre-specified radiation dose to the vessel wall, the whole system would then be removed and the sleeve disposed of. The deployment catheter can then be disposed of in an independent manner.

The sleeve can be housed in a small shielded delivery unit, which would be brought to the interventional laboratory (the site of the procedure). The catheter, when appropriately prepped and tested, would then be inserted into a port in the delivery unit and the sleeve locked in place. It is then placed via guidewire technique to the treatment site. When dosimetry is complete, the whole system then would be removed, the sleeve detached from the delivery system, the delivery system discarded in the usual manner, and the radioactive sleeve discarded in an appropriate radioisotopic disposal system.

Claims

CLAIMSWe claim:

1. A device for administering radiation therapy to a bodily vesicle, comprising a radiation-emitting sleeve having a tubular structure sized for internal delivery within the bodily vesicle and comprising a proximal end adapted for communicating with a distal end of a catheter, wherein the sleeve when in communication with the catheter is expandable from a first positioning diameter to a second larger radiation administration diameter, and is further retractable back to the first positioning diameter.

2. The device of Claim 1, wherein the sleeve comprises a visco-elastic polymer that is self-retractable.

3. The device of Claim 1, wherein the sleeve has a first positioning diameter of approximately 2 mm and a second administration diameter of approximately 8 mm.

4. The device of Claim 1, wherein the sleeve has a first positioning diameter of approximately 8 mm and a second administration diameter of approximately 14 mm.

5. The device of Claim 1, wherein the catheter comprises an expandable balloon on the distal end thereof.

6. The device of Claim 1, wherein the bodily vesicle is a blood vessel.

7. A method of administering radiation therapy to a bodily vesicle, comprising inserting into the vesicle a radiation-emitting sleeve having a tubular structure and comprising a proximal end in communication with the distal end of a catheter, wherein the sleeve when in communication with the catheter is expandable from a first positioning diameter to a second larger radiation administration diameter, and is further retractable back to the first positioning diameter; positioning the sleeve at a desired site for radiation therapy within the vesicle; expanding the sleeve to the second radiation delivery diameter; delivering the radiation therapy for a predetermined residence time; retracting the sleeve to the first positioning diameter; and withdrawing the sleeve from the bodily vesicle.

8. The method of Claim 7, wherein the sleeve comprises a visco-elastic polymer that is self-retractable.

9. The method of Claim 7, wherein the sleeve has a first positioning diameter of approximately 2 mm and a second administration diameter of approximately 8 mm.

10. The method of Claim 7, wherein the sleeve has a first positioning diameter of approximately 8 mm and a second administration diameter of approximately 14 mm.

11. The method of Claim 7, wherein the catheter comprises an expandable balloon on the distal end thereof.

12. The method of Claim 7, wherein the bodily vesicle is a blood vessel.

13. The method of Claim 7, wherein the radiation therapy is to alleviate undesired cellular growth.

14. The method of Claim 13, wherein the undesired cellular growth is angiogenesis.

15. The method of Claim 13, wherein the undesired cellular growth is restenosis.

16. The method of Claim 13, wherein the undesired cellular growth is cancer.