Surgery – Radioactive substance applied to body for therapy – Radioactive substance placed within body
Reexamination Certificate
2000-09-14
2002-05-21
Winakur, Eric F. (Department: 3736)
Surgery
Radioactive substance applied to body for therapy
Radioactive substance placed within body
C600S005000
Reexamination Certificate
active
06390967
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention relates generally to apparatus and methods for inhibiting restenosis in a blood vessel after an initial treatment for opening a stenotic region in the blood vessel. More particularly, the present invention relates to radiation treatment for inhibiting hyperplasia following balloon angioplasty and other intravascular interventional treatments.
Percutaneous translumenal angioplasty (PTA) procedures are widely used for treating stenotic atherosclerotic regions of a patient's vasculature to restore adequate blood flow. The catheter, having an expansible distal end usually in the form of an inflatable balloon, is positioned in the blood vessel at the stenotic site. The expansible end is expanded to dilate the vessel to restore adequate blood flow beyond the diseased region.
While PTA has gained wide acceptance, it continues to be limited by the frequent occurrence of restenosis. Restenosis afflicts approximately up to 50% of all angioplasty patients and is the result of injury to the blood vessel wall during the lumen opening angioplasty procedure. In some patients, the injury initiates a repair response that is characterized by smooth muscle cell proliferation referred to as hyperplasia in the region traumatized by the angioplasty. The hyperplasia of smooth muscle cells narrows the lumen that was opened by the angioplasty, thereby necessitating a repeat PTA or other procedure to alleviate the restenosis.
Many different strategies have been proposed to reduce the restenosis rate resulting from hyperplasia, including mechanical (e.g., prolonged balloon inflations during angioplasty, stenting, and the like), pharmacological, (e.g., the administration of anti-proliferative drugs following angioplasty), and other experimental procedures, all of which have had limited success.
As an alternative to mechanical devices and pharmacological drug delivery, use of intravascular radiotherapy (IRT) for the inhibition of hyperplasia following PTA has been proposed and is currently being commercialized. It has also been speculated that IRT may be used to prevent hyperplasia following cardiovascular graft procedures or other trauma to the vessel wall. Proper control of the radiation dosage is critical to impair or arrest hyperplasia without causing excessive damage to healthy tissue. Overdosing of a section of a blood vessel can cause arterial necrosis, inflammation, and hemorrhaging. Underdosing will result in no inhibition of smooth muscle cell proliferation, or even exacerbation of the hyperplasia and resulting restenosis.
A variety of catheters, guidewires, and stents have been configured for positioning a radioactive source within a blood vessel after angioplasty and other intravascular interventional treatments. In most cases, the devices have been configured to position a solid radioactive source, such as a wire, strip, pellet, or the like, within the blood vessel. It has also been proposed to deliver liquid radioactive medium to inflate a balloon catheter within the blood vessel. In the latter case, the balloon has been specially configured to prevent leakage of the radioactive material from the balloon into the blood vessel or blood stream. Of particular interest to the present invention, it has been proposed to use x-ray sources at the distal end of a catheter. The x-ray source permits convenient dosing where the source may be easily turned on and off and eliminates the need to prepare, handle, and dispose of radioisotopes.
While holding great promise, the use of radiation dosing to inhibit hyperplasia in blood vessels has not been entirely successful. In particular, hyperplasia will often still occur starting at the proximal and distal edges of an IRT treated blood vessel region and extending out 3 mm to 5 mm, producing so called “candy-wrapper” ends, as illustrated in FIG.
1
. It is speculated that non-uniform dose distribution at the proximal and distal edges of IRT catheters or stents is the most likely cause of this “candy-wrapper” effect. In particular, it is suggested that this high rate of cell growth at the ends is due to an interaction that occurs between blood vessel tissue beyond the IRT catheter or stent edges and a low radiation dose that results from a dose fall off on the edges. Radiation dose fall off at the ends, as shown in
FIG. 2
, results from the fact that the total radiation experienced by any point along the length of a blood vessel will depend on the amount and distance of all radioisotope sources on either side of it. For that reason, those points near the end of the length will necessarily receive less total radiation (i.e., from all points along the treatment region) than those near the middle. As such, use of current IRT catheters or stents is problematic since it can be difficult to provide delivery of a uniform radioactive dose throughout the blood vessel wall to prevent “candy-wrapper” ends.
Approaches to solving this “candy-wrapper” effect are currently under investigation. Primary studies have proposed increasing the dose of radiation at the edge to push the low dose exposure to an area beyond the region of injury to the vessel wall. Although irradiating beyond the region of injury appears to be working, the major drawback of this approach is that a majority of the vessel wall ends up being irradiated, including a considerable amount of non-damaged tissue. Further, as it is believed that a vessel can not be irradiated twice since dose is cumulative, future treatment problems may arise if restenosis occurs later in already irradiated tissue. Implanting a stent with a lower activity radioisotope in the middle and higher activity radioisotopes on the ends has also been suggested. However, this approach still suffers from radiation dose fall off on tissue which are close to the blood vessel and which encourage proliferative cell growth.
For these reasons, it would be desirable to provide improved devices and methods for inhibiting restenosis and hyperplasia following angioplasty and other intravascular interventional treatments. In particular, it would be desirable to provide improved apparatus, methods, and the like, for delivering radiation dosages to the blood vessel which are sufficiently uniform to prevent hyperplasia without encountering the “candy-wrapper” effect. Preferably, the improved devices and methods will be useful with all presently known modalities for delivering IRT to blood vessels including wire sources, pellet sources, liquid sources, x-ray sources, and the like. At least some of these objectives will be met by the present invention.
2. Description of the Background Art
Devices and methods for exposing intravascular and other treatment locations to radioactive materials are described in the following: U.S. Pat. Nos. 6,069,938; 5,971,909; 5,653,736; 5,643,171; 5,624,372; 5,618,266; 5,616,114; 5,540,659; 5,503,613; 5,498,227; 5,484,384; 5,411,466; 5,354,257; 5,302,168; 5,256,141; 5,213,561; 5,199,939; 5,061,267; and 5,059,166, European applications 860 180; 688 580; 633 041; and 593 136, and International Publications WO 97/07740; WO 96/14898; and WO 96/13303.
SUMMARY OF THE INVENTION
The present invention provides apparatus and methods for inhibiting hyperplasia in blood vessels after intravascular intervention. In particular, the methods can inhibit hyperplasia while reducing or eliminating the proliferative end effect, commonly called the “candy-wrapper” effect, which often accompanies such treatment.
The term “hyperplasia” refers to the excessive growth of the vascular smooth muscle cells which can result from an injury to the blood vessel wall resulting from angioplasty or other intravascular interventional procedures. The term “candy-wrapper” ends refers to a particular type of hyperplasia that often still occurs even in a radiotherapy treated blood vessel. As shown in
FIG. 1
, such “candy-wrapper” ends typically start at the proximal and distal edges of a treatment region and extend out 3 mm to 5 mm or more. “Candy-wrapper” ends may result from a non-uni
Forman Michael R.
Lovoi Paul A.
Rusch Tom W.
Townsend and Townsend / and Crew LLP
Winakur Eric F.
XOFT microTube, Inc.
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