(Circulation. 1995;92:2284-2290.)
© 1995 American Heart Association, Inc.
Articles |
Intra-arterial Beta Irradiation Prevents Neointimal Hyperplasia in a Hypercholesterolemic Rabbit Restenosis Model
From the Cardiology Center (V.V., P.U., J.B., M. Redard, M.C., M.-C.W., W.R.) and Division of Radiation Oncology (Y.P., M. Rouzaud, P.N., E.G., J.M.K.), University Hospital, Geneva, Switzerland; and Schneider (Europe) AG (M.S.), Bülach, Switzerland.
Correspondence to Philip Urban, MD, Cardiology Center, University Hospital, 1211 Geneva 14, Switzerland.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems.
Methods and Results Flexible 90-yttrium (90Y) coils inside a centering balloon were used to allow homogeneous intra-arterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245±93 cells/cm in control, 42±27 in 6 Gy, 72±107 in 12 Gy, and 2±2 in 18 Gy groups; P<.001) and in total neointimal cells (891±415 cells/cm in control, 79±43 in 6 Gy, 192±264 in 12 Gy and 22±13 in 18 Gy groups; P<.0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26±10% in the control group to 1±1.3% in the 18 Gy group (P<.0001), but lower doses had no significant effect.
Conclusions Administration of intra-arterial beta irradiation with a 90Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.
Key Words: irradiation • restenosis
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Despite recent encouraging results,1 2 restenosis after percutaneous transluminal coronary angioplasty remains a largely unresolved problem in contemporary cardiology. Several recent studies have shown the efficacy of intra-arterial gamma irradiation in animal models of postangioplasty restenosis3 4 and in human femoral arteries.5 6 7 We developed a technique of endovascular beta irradiation using pure metallic 90-yttrium (90Y) sources.8 9 10 11 The three major advantages of beta sources in comparison with conventional gamma sources used for brachytherapy are as follows: (1) markedly steeper dose decline in tissue, hence significantly lower undue irradiation of surrounding periarterial structures; (2) much lower half-value layer in water and other tissue-equivalent media eliminating to a large extent the radioprotection problems and making their use compatible with a conventional catheterization laboratory; and (3) possibility of a high focal dose delivery in a short time interval (1 to 5 minutes for 20 Gy) with sources of relatively low activity (40 to 100 mCi).
We used a hypercholesterolemic rabbit model of postangioplasty restenosis to investigate the feasibility of intraluminal 90Y irradiation and the efficacy of different dose schedules in preventing neointimal proliferation.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Radiation Delivery System
Flexible coils with an outer diameter of 0.36 mm (0.014 in) and 24 mm in length were specially manufactured from titanium-coated pure yttrium wire of 0.11-mm diameter (Fig 1A
). Both
tips of each coil were stretched over a length of 2 mm to form a
miniature thread, allowing fixation to a thrust wire. This wire served
for advancement, positioning, and withdrawal of the coil through the
lumen of a balloon catheter previously placed in the artery.
|
To provide
for a homogeneous intramural radiation dose
delivery, a special device (centering balloon) was developed to assure
optimal centering of the flexible 90Y source inside the
arterial lumen (Schneider AG). This device (Fig 1B
)
consists of a segmented balloon with four interconnected compartments
mounted on an over-the-wire coronary angioplasty
balloon shaft with an internal lumen diameter of 0.40 mm (0.016 in).
The 10-mm-long flexible tip of a conventional 0.014-in angioplasty
guide wire was fixed to the distal outlet of the balloon to ensure
complete sealing and to allow steering of the system.
The coils were activated in the neutron flux of a nuclear reactor to yield the pure beta emitter 90Y (half-life, 64.1 hours; maximal energy, 2.284 MeV). Each coil had an approximate activity of 45 mCi after activation. All animal experiments were done within 10 days after source activation in the nuclear reactor.
Dosimetric evaluation in a tissue equivalent phantom showed good axial and circumferential dose homogeneity on the surface of the centering balloon, with a standard deviation of the mean not exceeding 8%.9 10
The dose distribution in tissue for 90Y seeds has been studied previously.12 Our dosimetric study showed a similar curve of the dose falloff as a function of depth in a tissue-equivalent medium for a linear source presentation.8 This curve allows for accurate estimation of depth doses from surface dose measurements: For example, for a radiation dose of 10 Gy at the balloon surface, the dose will be 4 Gy at 1 mm of tissue depth, 1.5 Gy at 2 mm, and 0.8 Gy at 3 mm.
Study Animals
All experiments were performed with the
approval of the ethics
committee for animal experimentation of the University Hospital of
Geneva and the Cantonal Veterinary Office.
Twenty-one New Zealand White rabbits, 19 females and 2 males, 4 to 5 months of age, weighing 3.8±0.3 kg (range 3.2 to 4.5 kg), were used in the study.
Before the procedure and beginning from the age of 1 month, rabbits were fed a commercially available 2% cholesterol diet (Kliba) for 2 weeks followed by a 2-week period on a normal diet. This sequence was repeated 4 times, over a total of 16 weeks.13 After the procedure, a standard diet without cholesterol (Provimi) was fed to the animals.
Procedure
Under general anesthesia with ketamine (35
mg/kg) and xylazine (5 mg/kg), the left femoral artery was surgically
exposed in each animal. A transverse arteriotomy was performed distal
to one of the major deep femoral branches. The modified Baumgartner
technique of endothelial denudation was used to induce
neointimal proliferation.14 A
3.5-mm-diameter centering balloon, 20 mm in length, was inserted
into the lumen of the artery and advanced into the abdominal aorta.
Under fluoroscopic guidance, one of the carotid arteries (19 right and
2 left) was catheterized, and its middle third was externally marked
with a hypodermic needle. The centering balloon then was inflated with
contrast medium (Omnipaque 240) with its proximal tip at the marked
level and pulled back until its distal tip reached the mark. This was
repeated three times, leading to complete
deendothelialization of a 40-mm-long
arterial segment, as confirmed by our preliminary
experiments (unpublished data, 1994).
Afterward, the centering balloon
was positioned with its center in the
middle of the denuded arterial segment (level of the mark)
and left inflated for 360 seconds in all arteries. During inflation,
the 90Y source was advanced into the balloon and left in
this position (Fig 2) for the time necessary to apply
the calculated proposed surface dose. The exposure time increased for
each dose as a function of the time interval elapsed since source
activation in the reactor. For example, for arteries receiving a dose
of 18 Gy, exposure time varied between 105 seconds on day 2 and 322
seconds on day 9 (mean exposure time, 233±87 seconds).
|
The same procedure was performed in the left iliac artery. The fluoroscopically localized lumbosacral junction was used as an additional landmark of the distal balloon border position during the 360-second inflation.
In control arteries, all sequences of the procedure were performed except insertion of the 90Y source.
Radiation Schedules and Study End Points
The impact of 6 Gy,
12 Gy, and 18 Gy radiation doses
administered simultaneously with balloon dilatation was
studied. One carotid and one iliac artery were used in each animal,
forming four study groups: (1) control group, 11 arteries (5 carotids
and 6 iliacs); (2) 6 Gy group, 11 arteries (6 carotids and 5 iliacs);
(3) 12 Gy group, 10 arteries (6 carotids and 4 iliacs); and (4) 18 Gy
group, 10 arteries (5 carotids and 5 iliacs).
Ten animals were given an overdose of phenobarbital at 8 days and 11 at 6 weeks after intervention. A minimum of 5 vessels (3 carotids and 2 iliacs or vice versa) was obtained for each study group at each study end point.
Tissue Analysis
Application of Bromodeoxyuridine
Bromodeoxyuridine (BrdU) was given to each animal 18 and 12
hours before excision of the vessels. As described by Hanke et
al,15 16 100 mg/kg body wt BrdU and 75 mg/kg
deoxycytidine
(both from Sigma Chemie) were given as a subcutaneous neck depot 18
hours before the animals were killed. In addition to this,
intramuscular injections (30 mg/kg BrdU and 25 mg/kg body wt
deoxycytidine) were administered 18 and 12 hours before the animals
were killed.
Perfusion-Fixation
One hour before
perfusion-fixation, the rabbits were infused
intravenously with 60 mg/kg of Evans blue dye in
PBS.17 18 After application of a lethal dose of
phenobarbital, a thoracotomy was performed and the arteries were fixed
in situ with perfusion of 500 mL of 10% neutral buffered formalin
solution19 via a catheter inserted into the left
ventricle.
After 15 minutes of perfusion-fixation, the vessels of interest were excised and immersion-fixed in the same fixative for 4 to 6 hours, dehydrated in graded ethanol, and embedded in paraffin.19 Two samples from the central deendothelialized region of each artery (stained blue) were taken for cross sectioning. In the arteries studied at 6 weeks, two additional samples were obtained at 10 mm proximal and distal to the center of the blue area (usually corresponding to blue-white boundaries). The two samples from the middle of the deendothelialized region were considered to represent the middle of the denuded and dilated arterial segment and hence the center of the irradiated zone. The proximal and distal samples were considered to correspond to the position of the distal and proximal balloon extremities during the 360-second inflation. Sections were cut 4 µm thick, mounted, and stained with hematoxylin and eosin and Verhoeff–van Gieson (elastic) stain.
A monoclonal antibody against BrdU (DAKO), streptavidin-biotin system (Amersham International), and combined staining with diaminobenzidine and hemalaun were used to identify the cells entering the S-phase of mitosis within 24 hours before the animals were killed.
To allow for quantification of smooth muscle cell (SMC) proliferation in neointima and media of arteries at 8 days, all cells in the intima and media were counted in two adjoining cross sections of each sample. The percentage of DNA synthesis in SMCs in the media and intima was determined as the ratio between BrdU-labeled cells and the total cell number.15 16
All cross sections were morphometrically analyzed with the help of a computer-based Sigma-Scan V 3.90 software (Jandel Scientific). The areas of intima, media, and residual lumen as well as circumferences demarcated by internal and external elastic lamina were determined.
To quantify the degree of neointimal migration and proliferation at 8 days, the following indexes were calculated: (1) number of all neointimal cells per centimeter of internal arterial circumference; (2) number of BrdU-positive neointimal cells per centimeter of internal arterial circumference; and (3) number of BrdU-negative neointimal cells per centimeter of internal arterial circumference. The extent of stenosis at 6 weeks was determined as % area stenosis=(intimal area/intimal area+lumen area)x100%. In addition, the number of intimal cell layers at 6 weeks was determined by counting the number of cell nuclei on a perpendicular line between endothelium and internal elastic membrane in four neointimal regions equidistant from one another.
Statistical Evaluation
Data are expressed as mean±SD.
A one-way ANOVA was used to
test for an overall treatment effect. Leven's test was used to test
for equality of variances. In case of unequal variances, the Welch test
and Student's t test assuming unequal variances were used.
All probability values for pairwise comparison after a significant
one-way ANOVA were corrected according to Bonferroni. For
histological percent area stenosis, an arcsinus
transformation was performed. Differences were considered significant
at P<.05.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Twenty-one animals underwent interventions on 42 arteries. Two arteries (1 carotid after 18 Gy and 1 iliac from the control group) were found thrombosed at the time of histological examination and were excluded from analysis.
At 8 days, a marked and statistically significant decrease
(P<.0002) in total neointimal SMC number
percentimeter of inner arterial circumference was seen for
all radiation doses as compared with control arteries (Figs 3
and 4). The same was true separately
for BrdU-positive neointimal cells
(P<.001).
|
|
The internal elastic membranes of three control arteries were found to be completely covered by several layers of SMC at 8 days, which was not the case in any of the irradiated arteries. The percentage of neointimal BrdU-labeled SMCs was 54±15% (range, 30% to 72%) in the 6 Gy group and 27±18% (range, 1% to 45%) in the 12 Gy group, which was not statistically different from the control group (33±23%; range, 8% to 66%). In contrast, the same index was 10±6% (range, 3% to 15%) in the 18 Gy group, significantly lower than in the control group (P<.05). The percentage of medial BrdU-labeled SMCs was 7±3% (range, 4% to 12%) in the 6 Gy group, 16±20% (range, 0.6% to 50%) in the 12 Gy group and 4±3% (range, 1% to 7%) in the 18 Gy group, which was not statistically different from the control group (9±11%; range, 3% to 27%).
At 6 weeks, histological percent area stenosis
and number of neointimal cell layers (Fig 5)
were both significantly reduced (P<.0001 and
P<.03, respectively) in the group of arteries exposed to 18
Gy compared with the control group (Fig 6). There was no
significant reduction of these indices in the 6 Gy group or in the 12
Gy group.
|
|
For arteries irradiated with 18 Gy, the neointimal
formation was significantly reduced (P<.004) (Fig
7) in the area corresponding to the middle of the
balloon as compared with areas corresponding to proximal and distal
balloon borders. Furthermore, the regions corresponding to the distal
and proximal extremities of the irradiated zone showed a trend toward a
higher degree of percent area stenosis and an increased number
of neointimal cell layers in comparison with the middle of
the dilated region of control arteries.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Radiation Delivery System
Endoluminal brachytherapy is a promising technique for prevention of restenosis after percutaneous angioplasty. However, the approaches recently reported with 192Ir afterloading techniques in both animal models3 4 and in human femoral arteries5 6 have several readily apparent shortcomings: (1) The amount of unduly irradiated periarterial tissue is far from negligible with 192Ir brachytherapy. Liermann et al5 reported a dose of 12 Gy at 3 mm, 5.5 Gy at 6 mm, and 3 Gy at 10 mm from the source in tissue. This was without adverse effect on magnetic resonance imaging of perivascular tissues, however.6
(2) Appropriate radioprotection is an important obstacle for use of this technology in the setting of a conventional catheterization laboratory. Liermann et al5 describe transporting patients from the catheterization laboratory to the afterloading room situated in another building, adding 45 minutes to the duration of the procedure. The use of low dose rate 192Ir afterloading3 can alleviate this problem to some extent but at the cost of a longer intra-arterial exposure time (about 60 minutes for 20 Gy).
(3) Poor centering of the source within the arterial lumen precludes homogeneous intramural dosage delivery, resulting in areas of both relative underdosage and overdosage with respect to the prescribed dose level.6 This could be of clinical relevance, considering the possibility that modest radiation doses (4 to 8 Gy) might have a stimulatory effect on neointimal proliferation,20 21 22 whereas higher doses (20 to 30 Gy) could lead to late vascular complications.23 24
Although the use of beta irradiation (32P) for neointimal hyperplasia inhibition has been reported recently by others,25 26 to the best of our knowledge, we report11 the first successful in vivo use of endovascular beta afterloading for prevention of postangioplasty restenosis. The described approach allows all three shortcomings of 192Ir endovascular brachytherapy to be circumvented to a large extent.8 9 In addition, the use of yttrium permits fabrication of miniature flexible sources compatible with conventional angioplasty balloons and suitable for high dose rate afterloading in tortuous vessels of small caliber, such as the coronary arteries.
Radiobiological Aspects
Our study yields some insight into
the dynamic process of
cellular response of the arterial wall to different doses
of homogeneously delivered beta irradiation administered
simultaneously with balloon dilatation.
The initial inhibition of neointimal proliferation seen with all radiation schedules at 8 days was not confirmed at 6 weeks after intervention for arteries exposed to 6 and 12 Gy. A possible explanation for this phenomenon could be found in data obtained from in vitro studies of the cellular radiosensitivity of the aorta. It was shown by Fisher-Dzoga et al27 that the proliferative response of aortic medial SMCs was reduced only threefold by a radiation dose of 10 Gy. There is also evidence that partial recovery of irradiated SMCs occurs by the seventh postradiation day.27 The phenomenon of accelerated repopulation,28 well known to radiation oncologists, could theoretically even be responsible for an exaggerated cellular proliferation after low dose schedules. This could explain the putative stimulatory effect observed by others for radiation doses lower than 8 Gy,20 21 22 as well as the absence of long-term SMC inhibition at 6 or 12 Gy in our study.
The pattern of neointimal SMC inhibition reflects a significant decrease in cell migration from media to intima for all doses within 8 postradiation days. However, the percentage of neointimal BrdU-labeled cells after 6 and 12 Gy was not distinguishable from that of control cells. This would suggest that medial cells that succeed in traversing the internal elastic membrane, although reduced in number, have an intact potential for proliferation not distinguishable from that of control cells. In contrast, the 18 Gy dose was associated with a significant decrease in the percentage of BrdU-labeled medial SMCs, suggesting irreversible cell injury with reduced proliferative capacities.
Our study did not show a difference in the percentage of medial BrdU-labeled cells between irradiated arteries and control arteries at 8 days. A possible explanation for this is the observation that the internal elastic membranes of 3 control arteries were found to be completely covered by several neointimal SMC layers. Once it occurs, the maximum of SMC proliferation moves from media to intima, leaving only a very small number of proliferating cells in the media.17 18
The most striking finding in this study was the complete inhibition of neointimal hyperplasia at 6 weeks that was achieved in arteries treated with an 18 Gy radiation dose. The dynamics of neointimal progression in the animal model after arterial injury are now well established and show a maximal neointimal volume increase during the first 2 weeks after intervention, reaching a plateau phase by 4 to 6 weeks.15 18 This implies that an intramural arterial radiation dose of 18 Gy can be considered sufficient for induction of long-term inhibition of neointimal hyperplasia with the intra-arterial beta irradiation technique.
The increase at 6 weeks in the percent area stenosis and number of neointimal cell layers in regions corresponding to the borders of the irradiated zone may be of clinical relevance. Indeed, the intra-arterial longitudinal dose falloff along the long axis of the balloon, although very steep with a 90Y source, creates transitional areas of arterial wall irradiated with doses in an ineffective or even a potentially stimulatory range.20 21 22 In our experimental model, the injured arterial segment extended well beyond the irradiated zone, implying that a potential stimulatory effect of lower radiation doses was exerted over the injured regions of arterial wall. Taking into account that radiation doses of stimulatory range do not appear to induce neointimal proliferation in noninjured arterial segments,4 20 it seems reasonable to conclude from this observation that in clinical practice, the irradiated arterial segment should be at least as long as the dilated one and perhaps even slightly longer.
Study Limitations
Animal Model
The modified
Baumgartner technique of neointimal
hyperplasia induction was used in
hypercholesterolemic rabbits. This model allows for
accurate quantification of neointimal proliferation at both
early and late time points after the procedure, since the internal
elastic lamina remains intact and precise measurements of all
neointimal parameters are possible. However,
the cellular response to any given dose of radiation observed using
this model may well differ substantially from that of human arteries
with atheromatous plaques. Moreover, the degree to
which the hypercholesterolemic rabbit model can
predict the rate of short-term and long-term complications
after irradiation of human diseased coronary arteries is
unknown.
Complications
The intra-arterially
delivered beta irradiation
did not appear to influence the rate of acute and subacute
complications (thrombotic occlusions) in comparison with control
arteries. Although such events are not well documented in clinical
radiooncology, high single radiation doses focally delivered to the
arterial wall raise concern of late vascular complications
(such as thrombosis and aneurysm formation), potentially
life-threatening in coronary arteries. Our study does not
provide sufficient data nor was the observation period sufficiently
long to address this issue. It has been demonstrated that medial
necrosis and arteritis can occur in canine aortas and branch arteries
at doses above 20 Gy.23 24 Thrombus formations
covering
more than 25% of intimal surface and dissecting aneurysms were
observed in one half of the animals after 29 Gy and 32.5
Gy.23 24 Although these data derive from experiments
involving irradiation of large tissular volumes and may have limited
relevance for very localized endoarterial applications,
they highlight the necessity to address this problem in future
experiments with intra-arterial irradiation.
Optimal Dose
The Baumgartner model that was used led us to irradiate only part
of the denuded arterial segment. This could in theory
partly account for the lack of sustained suppression of the
proliferative response at 6 weeks in the lower dose schedules. Other
groups have found lower doses to be effective in preventing
neointimal proliferation in models of overstretch trauma to
pig coronary arteries and in human femoral
arteries.4 5 However, direct comparison with our own
data
is difficult because of markedly diverging depth-dose distribution
curves for beta and gamma sources.
Conclusions
Intra-arterial beta irradiation with pure
metallic
90Y sources is feasible and compatible with the setting of
an ordinary catheterization laboratory. Radiation doses
between 6 and 18 Gy effectively inhibit neointimal SMC
proliferation as assessed at 8 days in a
hypercholesterolemic rabbit model of
postangioplasty restenosis. This inhibitory
effect is lost during the following posttreatment weeks in arteries
that received radiation doses of 6 or 12 Gy. A radiation dose of 18 Gy
effectively induces long-term inhibition of neointimal
hyperplasia. The mild increase in neointimal proliferation
in areas proximal and distal to the balloon suggests that the
irradiated arterial segment should be at least as long as
the injured (dilated) arterial segment and perhaps even
slightly longer. The intra-arterially delivered beta
irradiation does not appear to influence the rate of acute and
subacute complications of the angioplasty procedure.
|
Acknowledgments |
|---|
This study was supported in part by Schneider-Europe AG (Bülach, Switzerland). We are indebted to Jurgen Fingerle, PhD (Hoffmann-La Roche Ltd, Basel, Switzerland), and to Akiko and Robert P. Hof, MD (Sandoz Ltd, Basel, Switzerland) for their advice and assistance in the preparation of the animal experiments.
Received December 28, 1994; revision received April 24, 1995; accepted May 18, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994;331:489-495.
2.
Stent Restenosis Study Investigators.
A randomized comparison of coronary-stent placement
and balloon angioplasty in the treatment of coronary artery
disease. N Engl J Med. 1994;331:496-501.
3. Wiedermann JG, Marboe CH, Amols H, Schwartz A, Weinberger J. Intracoronary irradiation markedly reduces restenosis after balloon angioplasty in a porcine model. J Am Coll Cardiol. 1994;23:1491-1498. [Abstract]
4.
Waksman R, Robinson KA, Crocker IR, Gravanis MB,
Cipolla GD, King SB III. Endovascular low-dose irradiation
inhibits neointima formation after coronary artery
balloon injury in swine. Circulation. 1995;91:1533-1539.
5. Liermann D, Böttcher HD, Kollath J, Schopohl B, Strassmann G, Strecker EP, Breddin KH. Prophylactic endovascular radiotherapy to prevent intimal hyperplasia after stent implantation in femoropopliteal arteries. Cardiovasc Int Radiol. 1994;17:12-16.
6. Böttcher HD, Schopohl B, Liermann D, Kollath J, Adamietz IA. Endovascular irradiation: a new method to avoid recurrent stenosis after stent implantation in peripheral arteries: technique and preliminary results. Int J Radiat Oncol Biol Phys. 1994;29:183-186. [Medline] [Order article via Infotrieve]
7. Liermann DD, Böttcher HD, Hermann G. Prophylactic endovascular radiotherapy of intimal hyperplasia in peripheral vessels. Cardiovasc Int Radiol. 1994;17(suppl 2):S97. Abstract.
8. Popowski Y, Verin V, Papirov I, Nouet P, Rouzaud M, Grob E, Schwager M, Urban P, Rutishauser W, Kurtz J. High dose rate brachytherapy for prevention of restenosis after percutaneous transluminal coronary angioplasty: preliminary dosimetric tests of a new source presentation. Int J Radiat Oncol Biol Phys. 1995;33:211-215. [Medline] [Order article via Infotrieve]
9. Popowski Y, Verin V, Papirov I, Nouet P, Rouzaud M, Grob E, Schwager M, Urban P, Rutishauser W, Kurtz J. Intra-arterial 90-yttrium brachytherapy: preliminary dosimetric study using a specially modified angioplasty balloon. Int J Radiat Oncol Biol Phys. In press.
10. Verin V, Popowski Y, Urban P, Nouet P, Rouzaud M, Schwager M, Kurtz JM, Rutishauser W. Intraarterial beta irradiation for prevention of post angioplasty restenosis. J Invasc Cardiol. 1995;7:12A. Abstract.
11. Verin V, Popowski Y, Urban P, Belenger J, Redard M, Costa M, Widmer M-C, Schwager M, Kurtz JM, Rutishauser W. Intraarterial beta irradiation prevents neointimal hyperplasia in a hypercholesterolemic rabbit restenosis model. J Am Coll Cardiol. 1995;(suppl):2A-3A. Abstract.
12. Dutreix A, Marinello G, Wambersie A. Dosimétrie des émetteurs bêta. In: Dutreix A, Marinello G, Wambersie A. eds. Dosimétrie en curiethérapie. Paris, France: Masson; 1982:191-218.
13. Hof RP, Hof A. Vasoconstrictor and vasodilator effects in normal and atherosclerotic conscious rabbits. Br J Pharmacol. 1988;95:1075-1080. [Medline] [Order article via Infotrieve]
14. Baumgartner HR. Eine neue Methode zur Erzeugung von Thromben durch gezielte Ueberdehnung der Gefaesswand. Z Ges Exp Med. 1963;137:227-230.
15.
Hanke H, Strohscheider T, Oberhoff M, Betz E, Karsch
KR. Time course of smooth muscle cell proliferation in the
intima and media of arteries following experimental
angioplasty. Circ Res. 1990;67:651-659.
16.
Hanke H, Haas KK, Hanke S, Oberhoff M, Hassenstein S,
Betz E, Karsch KR. Morphological changes and smooth muscle cell
proliferation after experimental eximer laser treatment.
Circulation. 1991;83:1380-1389.
17. Clowes AW, Reidy MA, Clowes MA. Kinetics of cellular proliferation after arterial injury. Lab Invest. 1983;49:327-333. [Medline] [Order article via Infotrieve]
18. Clowes AW, Reidy MA, Clowes MA. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208-215. [Medline] [Order article via Infotrieve]
19. Zeymer U, Fishbein MC, Forrester JS, Cercek B. Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation: comparison with tymidine and bromodeoxyuridine labelling. Am J Pathol. 1992;141:685-690. [Abstract]
20. Schwartz RS, Koval TM, Edwards WD, Camrud AR, Bailey KR, Browne K, Vlietstra RE, Holmes DR. Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury. J Am Coll Cardiol. 1992;19:1106-1113. [Abstract]
21. Wiedermann JG, Marboe CH, Amols H, Schwartz A, Weinberger J. Intracoronary irradiation: minimal effective dose for prevention of restenosis in swine. Circulation. 1994;90(suppl I):I-59. Abstract.
22. Mazur W, Ali MN, Dabaghi SF, Crinstead C, Abukhalil J, Paradise P, DeFelice CA, Schulz D, Berner BM, Fajardo LF, French BA, Raizner AE. High dose rate intracoronary radiation suppresses neointimal proliferation in the stented and ballooned model of porcine restenosis. Circulation. 1994;90(suppl I):I-652. Abstract.
23. Gillette EL, Powers BE, McChesnay SL, Withrow SJ. Aortic wall injury following intraoperative irradiation. Int J Radiat Oncol Biol Phys. 1988;15:1401-1406.[Medline] [Order article via Infotrieve]
24. Gillette EL, Powers BE, McChesnay SL, Park RD, Withrow SJ. Response of aorta and branch arteries to experimental intraoperative irradiation. Int J Radiat Oncol Biol Phys. 1989;17:1247-1255. [Medline] [Order article via Infotrieve]
25.
Fischell TA, Kharma BK, Fischell DR, Loges PG, Coffey
CW, Duggan DM, Naftilan AJ. Low-dose, ß-particle
emission from `stent' wire results in complete, localized
inhibition
of smooth muscle cell proliferation.
Circulation. 1994;90:2956-2963.
26. Laird JR, Carter AJ, Kufs WM, Hoopes TG, Farb A, Nott S, Fischell RE, Fischell DR, Virmany R, Fischell TA. Inhibition of neointimal proliferation with a beta particle emitting stent. J Am Coll Cardiol. 1994;(suppl):287A. Abstract.
27. Fischer-Dzoga K, Dimitrievich GS, Griem ML. Radiosensitivity of vascular tissue, II: differential sensitivity of aortic cells in vitro. Radiat Res. 1984;99:536-546. [Medline] [Order article via Infotrieve]
28. Hall EJ. Radiobiology for the radiologist. Philadelphia, Pa: JB Lippincott; 1994:219-221.
This article has been cited by other articles:
 |
|
 |
|
  M R Thomas Brachytherapy: here today, gone tomorrow? Heart, June 1, 2005; 91(suppl_3): iii32 - iii34. [Full Text] [PDF]
|
|
|
|
 |
|
 J. R Sindermann, V. Verin, J. W Hopewell, H. P. Rodemann, and J. H Hendry Biological aspects of radiation and drug-eluting stents for the prevention of restenosis Cardiovasc Res, July 1, 2004; 63(1): 22 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Hang, M. Fu, B.-T. Hsieh, S. W. Leung, C.-J. Wu, H.-K. Yip, and G. Ting Intracoronary {beta}-Irradiation With Liquid Rhenium-188: Results of the Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis Study Chest, October 1, 2003; 124(4): 1284 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.W. Serruys, G. Sianos, W. van der Giessen, H.J.R.M. Bonnier, P. Urban, W. Wijns, E. Benit, M. Vandormael, R. Dorr, C. Disco, et al. Intracoronary {beta}-radiation to reduce restenosis after balloon angioplasty and stenting. The Beta Radiation In Europe (BRIE) study Eur. Heart J., September 1, 2002; 23(17): 1351 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Kaluza, A. E. Raizner, W. Mazur, D. G. Schulz, J. M. Buergler, L. F. Fajardo, F. O. Tio, and N. M. Ali Long-Term Effects of Intracoronary {beta}-Radiation in Balloon- and Stent-Injured Porcine Coronary Arteries Circulation, April 24, 2001; 103(16): 2108 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.Y Salame, S Verheye, I.R Crocker, N.A.F Chronos, K.A Robinson, and S.B King III Intracoronary radiation therapy Eur. Heart J., April 2, 2001; 22(8): 629 - 647. [PDF]
|
|
|
|
 |
|
 V. Verin, Y. Popowski, B. de Bruyne, D. Baumgart, W. Sauerwein, M. Lins, G. Kovacs, M. Thomas, F. Calman, C. Disco, et al. Endoluminal Beta-Radiation Therapy for the Prevention of Coronary Restenosis after Balloon Angioplasty N. Engl. J. Med., January 25, 2001; 344(4): 243 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wohlfrom, J. Kotzerke, J. Kamenz, M. Eble, B. Hess, J. Wohrle, S. N Reske, V. Hombach, H. Hanke, and M. Hoher Endovascular irradiation with the liquid {beta}-emitter Rhenium-188 to reduce restenosis after experimental wall injury Cardiovasc Res, January 1, 2001; 49(1): 169 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.W. Serruys and S.G. Carlier Brachytherapy in the Journal: European cardiologists have their own forum and should use it! Eur. Heart J., December 2, 2000; 21(24): 1994 - 1996. [PDF]
|
|
|
|
|
|
A. E. Raizner, S. N. Oesterle, R. Waksman, P. W. Serruys, A. Colombo, Y.-L. Lim, A. C. Yeung, W. J. van der Giessen, L. Vandertie, J. K. Chiu, et al. Inhibition of Restenosis With {beta}-Emitting Radiotherapy : Report of the Proliferation Reduction With Vascular Energy Trial (PREVENT) Circulation, August 29, 2000; 102(9): 951 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sabate, M. A. Costa, K. Kozuma, I. P. Kay, W. J. van der Giessen, V. L. M. A. Coen, J. M. R. Ligthart, P. Serrano, P. C. Levendag, and P. W. Serruys Geographic Miss : A Cause of Treatment Failure in Radio-Oncology Applied to Intracoronary Radiation Therapy Circulation, May 30, 2000; 101(21): 2467 - 2471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sabate, J. P. A. Marijnissen, S. G. Carlier, I. P. Kay, W. J. van der Giessen, V. L. M. A. Coen, J. M. R. Ligthart, E. Boersma, M. A. Costa, P. C. Levendag, et al. Residual Plaque Burden, Delivered Dose, and Tissue Composition Predict 6-Month Outcome After Balloon Angioplasty and {beta}-Radiation Therapy Circulation, May 30, 2000; 101(21): 2472 - 2477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Waksman, B. Bhargava, L. White, R. C. Chan, R. Mehran, A. J. Lansky, G. S. Mintz, L. F. Satler, A. D. Pichard, M. B. Leon, et al. Intracoronary {beta}-Radiation Therapy Inhibits Recurrence of In-Stent Restenosis Circulation, April 25, 2000; 101(16): 1895 - 1898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I P Kay, M Sabate, G Van Langenhove, M A Costa, A J Wardeh, A L Gijzel, N V Deshpande, S G Carlier, V L M A Coen, P C Levendag, et al. Outcome from balloon induced coronary artery dissection after intracoronary beta radiation Heart, March 1, 2000; 83(3): 332 - 337. [Abstract] [Full Text]
|
|
|
|
|
|
P. S. Teirstein, V. Massullo, S. Jani, J. J. Popma, R. J. Russo, R. A. Schatz, E. M. Guarneri, S. Steuterman, K. Sirkin, D. A. Cloutier, et al. Three-Year Clinical and Angiographic Follow-Up After Intracoronary Radiation : Results of a Randomized Clinical Trial Circulation, February 1, 2000; 101(4): 360 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O F Bertrand, S Lehnert, R Mongrain, and M G Bourassa Early and late effects of radiation treatment for prevention of coronary restenosis: a critical appraisal Heart, December 1, 1999; 82(6): 658 - 662. [Full Text]
|
|
|
|
 |
|
 D. P Lee, S. Lo, K. Forster, A. C Yeung, and S. N Oesterle Clinical applications of brachytherapy for the prevention of restenosis Vascular Medicine, November 1, 1999; 4(4): 257 - 268. [Abstract] [PDF]
|
|
|
|
|
|
M. Sabate, I. P. Kay, W. J. van der Giessen, A. Cequier, J. M. R. Ligthart, J. A. Gomez-Hospital, S. G. Carlier, V. L. M. A. Coen, J. P. A. Marijnissen, A. J. Wardeh, et al. Preserved Endothelium-Dependent Vasodilation in Coronary Segments Previously Treated With Balloon Angioplasty and Intracoronary Irradiation Circulation, October 12, 1999; 100(15): 1623 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sabate, P. W. Serruys, W. J. van der Giessen, J. M.R. Ligthart, V. L.M.A. Coen, I. P. Kay, A. L. Gijzel, A. J. Wardeh, A. den Boer, and P. C. Levendag Geometric Vascular Remodeling After Balloon Angioplasty and {beta}-Radiation Therapy : A Three-Dimensional Intravascular Ultrasound Study Circulation, September 14, 1999; 100(11): 1182 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. O. Trerotola, T. J. Carmody, R. D. Timmerman, K. A. Bergan, R. G. Dreesen, S. V. Frost, and M. Forney Brachytherapy for the Prevention of Stenosis in a Canine Hemodialysis Graft Model: Preliminary Observations Radiology, September 1, 1999; 212(3): 748 - 754. [Abstract] [Full Text]
|
|
|
|
|
|
D. Meerkin, J.-C. Tardif, I. R. Crocker, A. Arsenault, M. Joyal, G. Lucier, S. B. King III, D. O. Williams, P. W. Serruys, and R. Bonan Effects of Intracoronary ß-Radiation Therapy After Coronary Angioplasty : An Intravascular Ultrasound Study Circulation, April 6, 1999; 99(13): 1660 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Teirstein, V. Massullo, S. Jani, R. J. Russo, D. A. Cloutier, R. A. Schatz, E. M. Guarneri, S. Steuterman, K. Sirkin, S. Norman, et al. Two-Year Follow-Up After Catheter-Based Radiotherapy to Inhibit Coronary Restenosis Circulation, January 19, 1999; 99(2): 243 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Waksman, J. C. Rodriguez, K. A. Robinson, G. D. Cipolla, I. R. Crocker, N. A. Scott, S. B. King III, and J. N. Wilcox Effect of Intravascular Irradiation on Cell Proliferation, Apoptosis, and Vascular Remodeling After Balloon Overstretch Injury of Porcine Coronary Arteries Circulation, September 16, 1997; 96(6): 1944 - 1952. [Abstract] [Full Text]
|
|
|
|
|
|
D. Brieger and E. Topol Local drug delivery systems and prevention of restenosis Cardiovasc Res, September 1, 1997; 35(3): 405 - 413. [Full Text] [PDF]
|
|
|
|
|
|
P. S. Teirstein, V. Massullo, S. Jani, J. J. Popma, G. S. Mintz, R. J. Russo, R. A. Schatz, E. M. Guarneri, S. Steuterman, N. B. Morris, et al. Catheter-Based Radiotherapy to Inhibit Restenosis after Coronary Stenting N. Engl. J. Med., June 12, 1997; 336(24): 1697 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Verin, P. Urban, Y. Popowski, M. Schwager, P. Nouet, P. A. Dorsaz, P. Chatelain, J. M. Kurtz, and W. Rutishauser Feasibility of Intracoronary ß-Irradiation to Reduce Restenosis After Balloon Angioplasty: A Clinical Pilot Study Circulation, March 4, 1997; 95(5): 1138 - 1144. [Abstract] [Full Text]
|
|
|
|
|
|
W. J. van der Giessen and P. W. Serruys ß-Particle–Emitting Stents Radiate Enthusiasm in the Search for Effective Prevention of Restenosis Circulation, November 15, 1996; 94(10): 2358 - 2360. [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||