WO1998025674A1

WO1998025674A1 - Method controlling dose rate during intravascular radiotherapy

Info

Publication number: WO1998025674A1
Application number: PCT/US1997/023177
Authority: WO
Inventors: Anthony J. Bradshaw; Richard V. Calfee
Original assignee: Guidant Corporation
Priority date: 1996-12-10
Filing date: 1997-12-10
Publication date: 1998-06-18
Also published as: AU5703898A; US5882291A

Abstract

A method is disclosed for treating a blood vessel which has been subjected to interventional dilatation, to inhibit restenosis that would otherwise occur from cellular proliferation attributable to traumatic response at the site of the vessel interior wall where the dilatation was performed. The method includes introducing a radioactive source into the blood vessel so that the source is positioned adjacent to the site, and exposing targeted tissue of the vessel interior wall at the site to said radioactive source for a period of time sufficient to deliver a prescribed dose of radiation to the tissue. The rate at which the prescribed dose is delivered to the targeted tissue is adjusted to positively assure that the rate is held in a range with an upper limit of about 60 rads per second. Dose rate adjustment is controlled by selectively setting the distance between the source and the targeted tissue, or by appropriately selecting the length of the source according to the length of the site of targeted tissue along the vessel interior wall, and/or by appropriately attenuating the radiation emitted by the source to a desired reduced magnitude at the site of the targeted tissue, to positively assure that the dose rate delivered to the targeted tissue will not exceed 60 rads per second.

Description

METHOD CONTROLLING DOSE RATE DURING INTRAVASCULAR RADIOTHERAPY

Background of the Invention

The present invention relates generally to intravascular radiotherapy, and

more particularly to improved devices and methods for delivering nuclear radiation therapy

to avoid restenosis in blood vessels that have been subjected to an interventional dilatation

procedure.

U.S. Patent No. 5,199,939 to Dake et al. discloses a technique for inhibiting

restenosis in a coronary artery following angioplasty by delivering nuclear radiation

therapy to the artery wall at the time or immediately after the angioplasty procedure is

performed.

In co-pending patent applications Serial Nos. 08/057,322, 08/339,950 and

08/467,711 of A.J. Bradshaw et al., which are assigned to a common assignee, and

incorporated herein by reference in their entirety, devices and techniques are disclosed for

improved delivery of intravascular radiotherapy by substantially centering the radioactive

source in the tortuous pathway of a coronary artery to provide a relatively uniform dose of

radiation to preselected tissue of the arterial wall at the target site in a substantially

circumferential band disposed a predetermined radial distance from the radioactive source.

It is essential that a uniform dose of radiation be delivered to the preselected tissue in the

designated circumferential band about the source, rather than a random or non-uniform

dose. Otherwise, tissue segments at locations on the interior surface of the wall closer to and further from the source would be overdosed and underdosed, respecctively.

Overdosing is to be avoided because it causes excessive vessel hemorrhaging, excessive

fibrous media thinning, and the possibility of aneurysm or other late radiation effects. J.

Weinberger et al. of Columbia University have suggested in a published study that

overdosing also may be slightly stimulative in some dose ranges. Underdosing should also

be avoided because it does not inhibit the proliferative cellular growth which is a traumatic

response to the initial interventional dilatation, and hence, does not substantially deter

restenosis.

In a clinical setting, it is desirable to administer the intravascular

radiotherapy in as short a time as is practicable, to avoid the blood flow reduction and other

factors which can lead to adverse consequences from leaving the catheter and radioactive

source (so-called source wire) in place in the coronary artery or other portion of the

vasculature for too long a time. Treatment time may be shortened by increasing the

activity level of the radioactive source.

Studies by the Frankfort Group and Emory University have indicated that

very high activity radioactivity sources stepped through the target site with relatively short

treatment times, i.e., where the source is of shorter length than the length of arterial wall

which is to be treated and must therefore be incrementally advanced (or retracted) — or

"stepped" — through the target site during treatment, have yielded mixed results. Neither

of these cited studies used techniques to assure centering of the radioactive source, and

each used a standard oncology catheter in delivery of the radiation. Research conducted by the applicants herein using a high activity stepping source without centering to treat

coronary arteries in pigs yielded mixed results, with the relatively straight circumflex

(CFX) and left anterior descending (LAD) arteries exhibiting a dose reponse with 1000

rads (r, or centiGray, cGy) which is similar to the control arteries. A better response was

achieved with 1500 r, and even better with 2500 r. In that regard, the term "better" is used

as reflecting improved results in percentage of area stenosis, in maximal intimal thickness,

and in mean luminal area, compared to control. The right coronary artery (RCA) results

showed no dose response and no improvement at any of the three doses, thought by the

applicants to be attributable to lack of dose control in this severely curved artery because

no centering mechanism was used to preclude random overdosing and underdosing.

Further testing and data analysis by the applicants has suggested another

mechanism responsible for the poor RCA results and the mixed results encountered in

other high activity studies. It is a primary objective of the present invention to provide

improvements in the methods and apparatus for inhibiting restenosis in blood vessels

subjected to angioplasty procedures.

Summary of the Invention

The applicants herein have discovered that the dose rate, i.e., the rate at

which the prescribed dose of radiation is delivered from the radioactive source to targeted

tissue at the interior of the vessel wall, to be effective, should not exceed 60 rads per

second. Radiation dosage exceeding this rate produces robust cellular proliferation, even in arteries which had not been previously subjected to dilatation and higher doses of

radiation. This proliferative effect, which is highly undesirable, is clearly evident in

previously dilatated pig arteries (e.g., balloon overstretch model), is dominant at doses which are

effective at lower dose rates, and causes the vessel lumen to be restricted and even to close

rather than to remain open as sought by the application of intravascular radiotherapy.

Accordingly, a method is provided for treating a blood vessel which has

been subjected to interventional dilatation, to inhibit restenosis that would otherwise occur

from cellular proliferation attributable to traumatic response at the site of the vessel interior

wall where the dilatation was performed. The method includes treating the patient to

irradiate targeted tissue along a length of the interior surface of the wall of a blood vessel

subjected to an interventional dilatation procedure, including prescribing a dose of

radiation to be delivered from a radioactive source to tissue along the length of interior

surface to inhibit cellular proliferation thereat, selecting a radioactive source having an

activity level sufficient to deliver the prescribed dose to the targeted tissue, placing the

radioactive source within the vessel adjacent to targeted tissue for a time interval required

to deliver the prescribed dose thereto, and mamtaining certain predetermined

characteristics of the source relative to the targeted tissue to assure that the prescribed dose

is delivered to the targeted tissue at a rate which does not exceed a maximum value of

approximately 60 rads per second at the prescribed treatment distance . The maintaining of certain predetermined characteristics of the source

relative to the targeted tissue includes selecting at least one of the configuration of the source, the position of the source in the vessel relative to targeted tissue, the distance

between the source and targeted tissue adjacent thereto, and the attenuation of radioactivity

emitted by the source at the adjacent targeted tissue, to limit the rate at which the

prescribed dose is delivered to targeted tissue so as not to exceed the specified maximum

value. Control of attenuation of radioactivity emitted by the source may be accomplished

by interposing sufficient radiation-attenuating material between the source and the targeted

tissue to limit the rate of delivery of the prescribed dose.

In a preferred method, the radioactive source is a beta emitter. Preferably

also, the radioactive source is a solid material secured to a thin, elongate, flexible line to

permit the source to be advanced into and retracted from the vessel from a control point

outside the patient's body, generally be means of a conventional afterloader which can be

operated from a remote location with respect to the patient being treated. Alternatively, the

radioactive source may comprise pellets, powder, or liquid, or even gaseous material.

Pellets, for example, may be introduced into a catheter under pressure from an external

device to position them in a desired location for treating targeted tissue. In yet another

form, the radioactive source may be implemented in the form of a stent which is implanted

in a blood vessel at the target site.

Brief Description of the Drawings

Although it is not necessary to present drawings to enable a full

understanding of the present invention, the above and still further objects, features, aims, and advantages of the invention will become apparent from a consideration of the

following detailed description of the invention, taken in conjunction with the

accompanying drawings, in which:

FIG. 1 is a side view, partly in section, of a radioactive source disposed in a

catheter in a portion of a blood vessel targeted for delivery of a prescribed dose of radiation

to tissue at the interior of the vessel wall, including means for centering the source in the

lumen of the vessel to assure a delivery of uniform dose to tissue in a circumferential band

of tissue of the interior wall about the radioactive source; and

FIG. 2 is a perspective view, in section taken along the lines 2-2 of FIG. 1.

Detailed Description of the Preferred Methods and Embodiments

As noted above, the present invention provides for the delivery of a

prescribed dose of nuclear radiation to targeted tissue at the interior surface of the blood

vessel wall site which has been subjected to a procedure for opening the lumen of the

vessel, as an interventional dilatation procedure, whether the opening is achieved by

performing an angioplasty procedure (using a balloon, a laser, or a rotating ultra-sharp

blade, for example), or by stenting, or by use of any other means. The targeted tissue

preferably lies in a substantially circumferential band about the radioactive source used to

deliver the radiation, the source being introduced into the patient's vascular system for

positioning at the target site within the blood vessel. The essence of the invention is that

the dose rate of the radiation to which the preselected tissue is subjected during delivery is pro-actively limited to a value not exceeding 60 rads per second.

It is important to understand clearly that limiting the dose rate is not the

same as limiting the dose which is prescribed by the attending physician or physicist for a

successful result of the procedure, as in inhibiting restenosis in the vessel in response to the

trauma suffered during an angioplasty procedure. Thus, the significance of the invention

lies in a recognition that although the dose absorbed by the preselected tissue may be

appropriate and in the amount prescribed, the radiation procedure will be unsuccessful,

and, indeed, may exacerbate the extent or onset (or both) of cellular proliferation sought to

be avoided, if the rate at which that dose is delivered exceeds a particular value, and

specifically, if the dose rate exceeds 60 rads per second.

Radiation dose is a function of the isotope (i.e., the energy spectrum and

tissue absoφtion for that energy), the distance of the target tissue from the radioactive

source, and the amount of time over which the target tissue is exposed to the radiation.

The device characteristics and the methods employed for limiting and controlling the dose

rate are described below.

One technique for setting the dose rate is to control the distance from the

radioactive source to the targeted tissue. Suppose, for example, that the dose prescribed for

absoφtion by the interior arterial wall tissue is 3000 rads, for a treatment length (of arterial

wall at the target site) of 30 millimeters (mm), and that the activity of the source on the

treatment day (i.e., source activity inevitably declines as a consequence of continuing

decay, unless recharged or reactivated by subjection to additional nuclear irradiation which is not practical for a source to be available at a treatment center (hospital or otherwise) for

use at any time during a predetermined period of suitable activity) is such that the

prescribed dose will be delivered in two minutes to a 4 mm diameter artery. The dose rate

is 1500 rads per minute (dose/time for delivery, or 3000/2), or 25 rads per second, provided

that the source is centered in the artery. As observed earlier herein, if the source is not

centered the tissue of the arterial wall will be subjected to overdosing at the side nearest the

source, and to underdosing at the side furthest from the source. In the latter circumstances,

the dose rate will vary accordingly, the rate being faster at the near side (higher dose

delivered in the prescribed time interval) and slower at the far side (lower dose delivered in

that same interval).

The dose is calculated, and the time interval over which the source is to be

situated in the treatment volume is determined, based on a measure of diameter of the

blood vessel obtained from fluoroscopy or from intravascular ultrasound. If the catheter is

not restrained and the source is placed against the wall of the catheter in the vessel, the

dose will approximately triple to 9000 rads, and so will the dose rate — to 75 r/sec. The

segment of the vessel wall in contact with the catheter may suffer radiation damage, in

addition to undergoing excessive cellular proliferation in less than 30 days, which may

negate some or all of the gain in lumen area that had been achieved by virtue of the original

angioplasty that had prompted the need for radiation treatment.

To overcome this problem, the source should be maintained at a known

minimum distance from the targeted tissue, preferably centered radially in the dilitated targeted segment or portion of the length of the artery by use of a balloon catheter 10 with

a corrugated balloon membrane 12 whose undulations (such as 13, 14) permit a flow-

through of blood in the trough between each pair of crests to enable perfusion when in

place and inflated in the blood vessel, as shown in FIGS. 1 and 2. Although not clearly

shown in the Figure, each trough is fastened to the catheter 10 internally of the membrane

12 to maintain an open passage for blood flow externally of the membrane. A lumen 15 of

the balloon catheter is substantially centered longitudinally in the blood vessel 17 so as to

also center the radioactive source 18 of a source wire 19, which is to be advanced and

retracted via balloon catheter 10 during use throughout the radiotherapy procedure. The

source is centered in lumen 15 of the catheter, and since the lumen of the catheter is

centered in the vessel (with appropriate biasing at 20 to compensate for the offset of lumen

15 from the longitudinal center of the balloon membrane), the source is also centered

longitudinally in the vessel. The centering scheme tends to assure that targeted tissue at

the site of the interventional dilatation of the blood vessel lumen will be uniformly

irradiated in a circumferential band about the radioactive source, as disclosed in the

aforementioned co-pending applications 08/057,322, 08/339,950 and 08/467,711. A pair

of additional lumens 21 and 22 are used for a guidewire and for balloon inflation/deflation,

respectively.

Another technique for setting the dose rate is to control or mandate the

configuration of the radioactive source relative to configuration of the selected tissue. To

that end, the source length is set according to the length of the artery wall segment to be treated. For example, assume that the source in the above illustration is centered at a

known minimum distance from the target. If the source is 10 mm long, it must be stepped

longitudinally so that the dose of 3000 rads may be delivered in two minutes to the 30 mm

long segment of the 4 mm diameter artery. In particular, the source must be stepped

through three sequential 10 mm positions along the 30 mm targeted segment of the artery

wall, within a two minute period. In those circumstances, however, the dose rate to the

target or preselected tissue along the length of the arterial wall segment being treated

would be 75 r/sec, since each one-third portion of that segment must receive a prescribed

dose of 3000 rads during the short interval that the source is adjacent that portion (3000

rads/2 mins ÷ 60 sees ÷ 1/3 = 75 r/sec).

In this instance, the solution to maintaining the dose rate below the 60 r/sec

limit is to increase the length of the radioactive source sufficiently to make it more nearly

equal to the length of arterial wall segment to be treated. In particular, the source length

should be increased (i.e., by selecting the length in advance according to the measured

length of segment of the arterial wall to be treated) so that any segment of the smallest

artery which is anticipated to be treated with radiotherapy will receive the prescribed dose

of radiation at a dose rate which is less than 60 r/sec. The length of the source need not be

the same as the length of the vascular wall segment or portion to be treated; only a length

sufficient to assure that the dose rate is less than that maximum value. Yet another technique for controlling the dose rate is to employ a suitable

radiation attenuating material between the source and the tissue to be treated, such that the

dose rate applied to the target tissue is appropriately limited to a value less than 60 r/sec.

For illustration, assume that access is available to only a high activity oncology

brachytherapy device to perform peripheral vascular procedures, or, alternatively, that an

unusually small vessel is to be treated with the beta source coronary intravascular

radiotherapy system of the previous example. In either case, the dose rate for tissue

located at the target distance from the source is likely to exceed 60 r/sec. The solution to

this problem is to employ radiation-attenuating material in the treatment catheter that will

adequately reduce the rate at which the prescribed dose will be delivered to the targeted

tissue, to a value below the specified upper limitation.

For example, the catheter material may be modified to contain a high Z

filler (high density) such as barium for beta sources, or materials such as a wound coil

layer of tungsten wire through the treatment length of the catheter to appropriately

attenuate gamma radiation-emitting sources. Alternatively, or additionally, the balloon

centering device could be filled with an appropriate attenuating liquid. In all such cases,

the radiation-attenuation characteristics of the material must be known and taken into

consideration for calculation of the dose rate that will then apply for the particular source

which is used in the radiotherapy procedure. It is to important to note that different

materials have drastically different attenuation properties relative to the entire family of

radioactive isotopes. The idea is to utilize attenuating material in the treatment catheter or other convenient region between the source and the targeted tissue as necessary to reduce

the dose rate to an acceptable level, without substantially impeding perfusion at the target

site.

As has been noted above in the summary of the invention, the radioactive

source need not be restricted to a source wire with a solid source fastened to a thin,

elongate, flexible line, although that is the preferred configuration. Instead, the source may

be implemented in alternative form, such as pellets which are injected by hydraulic means

after the catheter is installed in the blood vessel, or any other known form described in the

prior art, including powder, liquid, or gas. The source may be carried by a stent which is

deployed to provide the interventional dilatation to hold open the venous lumen.

In the aforementioned Dake et al. '939 patent, an exemplary treatment is

described in which the prescribed maximum dose is about 2500 rads, and the maximum

dose rate is about 10,000 rads per hour (equivalent to about 2.78 rads per second) measured

at 3 mm from the longitudinal central axis of the carrier. That maximum dose described in

Dake et al. can be delivered in 15 minutes to tissue located at 3 mm from the central axis

(and from the source, if the source is positioned at the central axis), i.e., 2500 rads ÷ 2.78

rads per second = 899 seconds (substantially equivalent to 15 minutes). For targeted tissue

closer to the radioactive source than 3 mm, the dose rate presumably would increase. If a

phosphorus isotope (P³²) were used as the source, the dose rate at a point located 1 mm

from the source would be approximately 31 r per sec, which is well within the maximum

dose rate of 60 r/sec according to the present invention. However, the maximum dose of 2500 rads in Dake et al may be insufficient for beta emitting sources, depending on how

the Dake et al. point of prescription for dose is inteφreted.

Animal studies conducted by the applicants herein, using the beta emitter

P³² in pig coronary arteries, have shown that at least about 2000 rads are needed at the

adventia to inhibit cellular proliferation and resultant lumen shrinkage. A dose of 2000 at

the adventia requires a dose at the vessel surface of at least about 2750 rads. The Dake et

al. disclosure does not indicate the precise point in the vessel wall for which such a dose

would be prescribed, nor teach a maximum dose as great as 2750 rads. Indeed, other

researchers have speculated that the effective dose is less than 2500 rads. Other beta

emitters such as Yttrium 90 (Y⁹⁰) and Strontium 90 (Sr⁹⁰, which produces the daughter of

Y⁹⁰) have slightly higher maximum energies and therefore exhibit slightly different dose

rates at distance curves than P³², but the same dose and dose rate requirements are present.

Good results have been produced by the applicants herein with 3000 rads to

the adventia (even up to about 4800 rads) without significant radiation damage to the

vessel in the treated area. The results were found to be good in both balloon injured

arteries and in arteries where a stent had been placed prior to irradiation. The results were

achieved using a centering balloon, and the effective doses for beta emitters were found to

be much higher than had been speculated in the prior art.

Even though the required dose is higher than anticipated by Dake et al. and

others, it remains highly desirable to hold the treatment time to less than 15 minutes, and

preferably less than 10 minutes. A beta source may be chosen from the group comprising P³², Y⁹⁰, and Sr⁹⁰, or the predominant beta emitter tungsten 188 (W⁸⁸) or daughter rhenium

188 (Re¹⁸⁸). The dose to be delivered should be in the range of at least about 2000 rads to

as much as about 5000 rads to a point about 0.5 mm deep into the surface of the artery

lumen along the entire length of a previously dilatated artery, at a dose rate not exceeding

60 r/sec, with a total treatment time of 15 mins (preferably 10 mins) to deliver the dose. A

minimum dose rate may be calculated as nominally about 3.1 r/sec ((2750 rads/ 15 mins) ÷

60 sees), making a usable dose rate range according to the present invention of from about

3.0 to about 60 r/sec. A point located at 0.5 mm deep into the interior surface of the artery

adjacent the lumen serves for present puφoses to describe the adventia generically, but

disregards the fact that in a previously dilatated artery the plaque makes the distance to the

adventia vary relative to the center of the resultant lumen after angioplasty.

The effective dose of gamma emitting sources appears to be less than that of

the beta emitting sources, which is probably attributable to the greater dose to the adventia

relative to the surface dose, as the activity of gamma emitters does not drop off as rapidly

as that of beta emitters. In any event, although it is not altogether clear that the maximum

dose rate for gamma emitters is 60 r/sec, for puφoses of the claims herein it is assumed

that such threshold applies to the gamma sources as well as the beta sources.

Although certain preferred embodiments and methods have been disclosed

herein, it will be apparent from the foregoing disclosure to those skilled in the art that

variations and modifications of such embodiments and methods may be made without

departing from the true spirit and scope of the invention. Accordingly, it is intended that the invention shall be limited only to the extent required by the appended claims and the

rules and principles of applicable law.

Claims

What is claimed is:

1. In a method for treating a blood vessel which has been subjected to

interventional dilatation, to inhibit restenosis that would otherwise occur from cellular

proliferation attributable to traumatic response at the site of the vessel interior wall

subjected to the dilatation, the steps of:

introducing a radioactive source into the blood vessel so that the source is

positioned adjacent to tissue targeted for treatment at said site,

exposing targeted tissue of the vessel interior wall at said site to said

radioactive source for a predetermined period of time sufficient to deliver a prescribed dose

of radiation to said tissue,

controlling the rate at which the prescribed dose is delivered to the targeted

tissue to actively maintain the dose rate in a range up to a maximum value of about 60 rads

per second, and

withdrawing the radioactive source from the blood vessel after said

prescribed dose has been delivered to the targeted tissue.

2. The method of claim 1, further including, during the step of exposing

the targeted tissue to said radioactive source, substantially centering said radioactive source

in the lumen of the blood vessel at said site to provide substantially uniform delivery of

radiation to the targeted tissue within a circumferential band about the radioactive source.

3. The method of claim 1, including using a beta radiation emitter as the

radioactive source.

4. The method of claim 1, including using a gamma radiation emitter as

the radioactive source.

5. The method of claim 1, wherein the step of controlling the dose rate

includes at least one of controlling the distance between the source and the targeted tissue,

controlling the configuration of the source according to the configuration of the targeted

tissue, and controlling the attenuation of radiation delivered to the targeted tissue, to

positively assure that the dose rate delivered to the targeted tissue does not exceed 60 rads

per second.

6. The method of claim 1, wherein the radioactive source is secured to a

thin, elongate, flexible line for advancement and retraction of the source into and from the

blood vessel in the course of treatment.

7. A method for inhibiting restenosis at a target site in a coronary artery

which has undergone an angioplasty procedure, including the steps of:

prescribing a dose of radiation to be delivered to targeted tissue of the arterial wall about a preselected radioactive source to be positioned at said site within said

coronary artery,

positioning the radioactive source at said site within the coronary artery, and

controlling at least some of the relative characteristics of the radioactive

source and the targeted tissue so that the prescribed dose of radiation is delivered to the

targeted tissue at a rate which is limited to reside in a rate range up to about 60 rads per

second.

8. The method of claim 7, wherein the step of positioning the source

includes substantially centering the source in the lumen of said coronary artery at the

targeted site for substantially uniform delivery of radiation to targeted tissue at the site

within a circumferential band at a fixed radial distance from said source.

9. The method of claim 7, including using a beta radiation emitter as said

radioactive source.

10. The method of claim 7, including using a gamma radiation emitter as

said radioactive source.

11. The method of claim 7, wherein the relative characteristics to be

controlled include at least one of (a) the distance between the source and the targeted tissue, (b) the relative lengths of the source and the targeted tissue along the arterial wall,

measured at a point occupied by the targeted tissue closest to the source.

12. The method of claim 7, wherein the radioactive source is secured to an

elongate, flexible line for advancement and retraction of the source into and from the artery

in the course of treatment.

13. A method of treating a portion of the interior wall of a blood vessel

which has undergone an interventional dilatation procedure, including the steps of:

prescribing a measured dose of radiation to be delivered from within the

blood vessel to tissue of said portion of the interior wall, to inhibit cellular proliferation

thereat,

inserting a radioactive source having an activity level sufficient to deliver

said prescribed dose into the blood vessel for positioning adjacent to designated tissue of

said portion, and

actively limiting the rate at which the prescribed dose is delivered to the

designated tissue to a rate range with an upper limit of about 60 rads per second, by

controlling at least one of the configuration of said source relative to the configuration of

the designated tissue of said portion, or the distance between said source in the blood

vessel and the designated tissue of said portion of the interior wall, or the amount by which the radiation emitted by the source is attenuated as it impinges on designated tissue of said

portion.

14. The method of claim 13, wherein the amount by which the radiation is

attenuated is controlled by inteφosing radiation-attenuating material between said source

and said designated tissue which is sufficient to maintain the rate of delivery of the

prescribed dose in said range and below said upper limit.

15. The method of claim 13, including using a beta emitter as the

radioactive source.

16. The method of claim 13, including using a gamma emitter as the

radioactive source.

17. The method of claim 13, including using as a radioactive source

secured to an elongate, flexible line for source advancement into and retraction from said

vessel.

18. A method of treating a patient to irradiate targeted tissue along a length

of the interior surface of the wall of a blood vessel subjected to an interventional dilatation

procedure, including the steps of: selecting a radioactive source having an activity level sufficient to deliver a

prescribed dose of radiation to targeted tissue along said length of interior surface to inhibit

cellular proliferation thereat, and

positioning the selected radioactive source within said blood vessel adjacent

to targeted tissue for a time interval required to deliver said prescribed dose to the targeted

tissue based on the distance between the source and the targeted tissue, the length of the

source relative to the length of the targeted tissue along said length of interior surface, and

the amount by which radiation emitted by the source is attenuated when it reaches the

targeted tissue, and adjusting at least one of said distance, said source length, and said

attenuation to assure that the prescribed dose is delivered to the targeted tissue at a rate

which does not exceed 60 r/sec.

19. The method of claim 18, wherein adjusting the attenuation of

radioactivity emitted by said source comprises inteφosing additional radiation-attenuating

material between said source and the targeted tissue to limit the rate of delivery of said

prescribed dose.

20. The method of claim 18, including selecting a beta emitter as the

radioactive source.

21. The method of claim 18, including selecting a gamma emitter as the radioactive source.

22. The method of claim 18, including selecting a radioactive source

secured to a thin, elongate, flexible line to permit advancement of the source into and

retraction from said vessel from a control point outside the patient's body.

23. The method of claim 18, including limiting the rate of delivery of the

prescribed dose to targeted tissue to a rate range from not less than about 3 r/sec to not

more than 60 r/sec.