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1 Department of Radiology, Hôpital Universitaire Tenon, AP-HP, 4, rue de
la Chine, F-75970 Paris Cedex 20, France.
2 Centre de Recherche en Imagerie d'Intervention (CRII), AP-HP, Institut
National de la Recherche Agronomique (INRA) F-78352 Jouy-en-Josas Cedex,
France.
3 Department of Pathology, Hôpital Universitaire Lariboisière,
AP-HP, 41, Blvd. de la Chapelle, F-75475 Paris Cedex 10, France.
4 Department of Medical Physics, Institut Gustave Roussy, 39, rue Camille
Desmoulins, F-94805 Villejuif Cedex, France.
5 Unité 141 of the Institut National de la Santé et de la
Recherche Médicale (INSERM), Hôpital Universitaire
Lariboisière, F-75475 Paris Cedex 10, France.
Received December 8, 2000;
accepted after revision March 8, 2002.
Address correspondence to A. F. Le Blanche.
Abstract
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MATERIALS AND METHODS. Twenty-one New Zealand white rabbits (10 females and 11 males) weighing an average of 3.5 kg (range, 3.2-3.8 kg) who had been fed a normal diet underwent bilateral 33% overdilatation with deendothelialization of the renal arteries. After 7 weeks, the induced renal artery stenoses were treated by percutaneous transluminal renal angioplasty. The rabbits were randomly assigned to one of three groups before receiving endovascular 25-Gy irradiation at a radial 2.0-mm depth with a 0.5 x 15 mm 198Au wire (106 MBq). The right renal artery was irradiated in group A; the left, in group B. The rabbits in group C randomly received a right- or left-sided dummy wire. Operator exposure to radiation was measured using thermoluminescent dosimeters and ionization chambers. The rabbits were sacrificed after 3 weeks. The aorta and renal arteries were perfusion-fixed. The renal arteries were removed for histologic and histomorphometric study.
RESULTS. Forty-two renal arteries were cut into a series of 4-µm-thick slices. Five arteries were thrombosed (two in the irradiated group and three in the control group, p > 0.05). In the patent arteries (n = 37), the average neointimal area was 0.068 mm2 (range, 0.009-0.234 mm2) in 15 irradiated segments (315 slices total), whereas the average neointimal area was 0.135 mm2 (range, 0.016-0.324 mm2) in 22 control segments (462 slices total) (analysis of variance, p < 0.009), showing a percentage area of restenosis of 10.4% in irradiated arteries and 43.4% in non-irradiated arteries (p < 0.0003). Radiation dose per procedure to the operator was 0.034 mSv in the index finger, 0.024 mSv in the wrist, and undectable in the body.
CONCLUSION. Endovascular brachytherapy with 198Au appears to inhibit early renal artery restenosis and exposes the operator to a safe level of radiation.
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Emitters of gamma photons or beta particles (i.e., electrons or positrons) seem to be potential preventive agents for restenosis, in the form of wires [9], seeds, liquid sources [10], or radioactive stents [11]. Endovascular gamma irradiation after percutaneous transluminal angioplasty of coronary arteries has been found to be effective in the prevention of restenosis during a 3-year follow-up period [12]. Beta-ray emitters have two advantages over gamma-ray emitters: the short radial particle range of beta-ray emitters induces a dramatic fall-off in tissue but produces low irradiation of surrounding structures, and beta-ray emitters can deliver high doses of irradiation in a short period of time from sources emitting moderate levels of radioactivity [9, 13].
However, among the beta-ray emitters, strontium-90-yttrium-90 are contaminating elements that are coated with titanium in their commercially available presentation used for catheterization, and phosphorus-32, although readily available as a liquid source, may metabolize into dangerous compounds if the delivery balloon is ruptured [14]. Iridium-192 is actually both a gamma- and beta-ray emitter with a low-energy beta-ray-emitting component; its use as a source of low-dose gamma rays in conventional catherization facilities requires delivery of the irradiation dose for more than 1 hr. Iridium-192 high-dose-rate delivery, although more rapid, requires the transfer and confinement of the patients inside a bunker, resulting in fewer clinical safety resources for the practitioner [15}. Gold-198 is a gamma- and beta-ray emitter with a low-energy gamma-ray-emitting component [11].
To our knowledge, endovascular brachytherapy has been used in renal venous strictures but not in renal arteries [16]. A new model of endovascularly induced renal artery stenosis was recently developed in rabbits [17]. Until now, only the coronary arteries of swines [13] or the iliac, femoral, and carotid arteries of rabbits have been studied [9], and these results have been considered to be applicable to renal arteries. However, the distribution of smooth muscle cells and elastic fibers inside the artery wall varies with the flow patterns of the artery [18], and it is likely that the severity of the response to angioplasty depends on the type of artery dilated.
Our study was designed to determine the efficacy of renal intraarterial 198Au endovascular brachytherapy in the prevention of early restenosis of the renal artery after percutaneous transluminal renal angioplasty in rabbits and to evaluate the radiation dose delivered to the operator.
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We chose 198Au for our study because it has predominant beta-ray-emission properties and a low-energy gamma-ray-emitting component, theoretically offering good radioprotection. Twenty-one adult New Zealand white rabbits (10 females and 11 males) weighing an average of 3.5 kg (range, 3.2-3.8 kg) who had been fed a regular rabbit chow ad libitum were our study population.
Radiation Delivery System
The intraarterial gamma-ray and beta-ray radiation source consisted of a
15-mm-long 198Au gamma- and beta-ray-emitting wire (0.0578 g;
half-life, 2.7 days; maximal beta energy, 0.961 MeV [99%]; average gamma
energy, 0.412 MeV [96%]) with an outer diameter of 0.5 mm, obtained by
activation under a thermal neutron flux—2.76 x 1013
neutrons x cm-2 x sec-1 for 5 min—in a
nuclear reactor. The delivery system was a 2.9-French catheter (Balt,
Montmorency, France; lumen diameter, 0.35 mm; wall thickness, 0.125 mm). The
radiation source was pushed towards the occluded end of the catheter by a
0.021-inch (0.5-mm) stiffening guide wire (Terumo, Tokyo, Japan).
Dosimetry
Dosimetric simulation was performed by computing the dose distribution from
previous data on 198Au brachytherapy
[20]. The source (106 MBq) was
modeled according to a beta-point source dose function
[21]. The absorbed dose rate
(DR) at a distance of x mm was obtained by the following
formula: DRx = DRs x
e-µx, with DRs being the absorbed
dose rate at the surface of the source and µ being the apparent absorption
coefficient in water. The exponential function of (-µx) is
expressed as e-µx. The maximal range of beta particles
for 1 MeV of energy is close to 4 mm in water. The radiation dose from gamma
photons was considered to be negligible because of their weak average
energy.
Radioprotection
All procedures were performed by two operators under the control of a
physicist. Each operator wore all usual tools of radiation protection.
Thermoluminescent dosimeters, film dosimeters, and two ionization chambers
were used. Dose rates, exact distances, and exposure times were noted. Because
of the rapid dose fall-off of beta-ray emitters over distance, the dose
resulting from beta particles is considered to be negligible beyond a distance
of 80 cm (through air) [22].
The measurements performed beyond a 1-m distance, therefore, concerned only
gamma and X rays.
Model Induction
We used a variant of a previously described endovascularly induced renal
artery stenosis model [17]. In
this variant, we used a femoral percutaneous approach and an 18-gauge needle
to introduce a 0.021-inch (0.5-mm) guidewire and a 4-French sheath (Terumo)
into the mid femoral artery. A 5-mm-long nonstenotic reference segment was
preserved (Fig. 1A).
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Percutaneous Transluminal Renal Angioplasty 7 Weeks After Stenosis
Induction
After 7 weeks, the rabbits were treated with aspirin (5 mg/24 hr) for 48 hr
before therapeutic percutaneous transluminal renal angioplasty to reduce the
risk of thrombosis or ischemia
[23]. After bilaterally
induced stenotic lumen irregularities were identified in the renal arteries on
angiograms, therapeutic percutaneous transluminal renal angioplasty was
performed bilaterally in the renal arteries. A 2.0 x 20 mm coronary
angioplasty balloon catheter was inflated to 10.1 x 105 Pa
for 30 sec at a site just beyond the prestenotic reference segment. The renal
arteries were not deendothelialized at this step of the experiment. The
location of the middle of the balloon was marked externally with a 23-gauge
needle, which was inserted into the skin and remained in place until
brachytherapy was performed (Fig.
1B). A second angiogram was then acquired to assess the immediate
postprocedural patency of the renal artery.
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Irradiation After Percutaneous Transluminal Renal Angioplasty
Irradiation was performed immediately after percutaneous transluminal renal
angioplasty. During irradiation, the rabbits were placed in the supine
position on the angiography table under a 1-cm-thick acrylic tunnel (beta-ray
protection) and surrounded by 2-cm-thick lead screens (gamma-ray protection).
The rabbits then were randomly divided into three groups—A, B, and
C—immediately after therapeutic percutaneous transluminal renal
angioplasty. The right renal artery was irradiated in group A and the left
renal artery was irradiated in group B. Group C received a dummy wire,
randomly placed in either the right or left side. In rabbits of groups A and
B, the renal artery contralateral to wire placement served as a control
artery. In group C, both renal arteries were controls. A 3.6-French curved
carrier sheath (Cook, Bloomington, IN) was advanced into the renal artery
selected for irradiation. The location of the delivery system was tracked with
fluoroscopy so that the middle of the source wire was in exactly the same
position as the middle of the balloon (which had been marked with the 23-gauge
needle) (Fig. 1C). Therefore,
only 15 mm of the 20-mm-long dilated portion of the artery was
irradiated—that is, a 2.5-mm-long segment at each extremity of the
dilated portion was less irradiated. The 0.7-mm-diameter endovascular
brachytherapy delivery system did not become wedged into the dilated (2-mm
diameter) renal arteries. We planned for all vessels to receive 25 Gy at a
radial 2.0-mm depth. After irradiation, the endovascular access equipment was
withdrawn, and the groin was manually compressed for 10 min. The rabbits were
thereafter kept in individual housing on an aspirin-free diet.
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Postirradiation Evaluation of Restenosis
The goal of the study was to evaluate the impact of irradiation on patent
stenotic renal arteries treated by percutaneous transluminal renal
angioplasty. After a 3-week period (representing the time interval to reach
the maximal inflammatory response of the arterial wall after percutaneous
transluminal renal angioplasty), the rabbits were deeply anesthetized by IV
injection of 50 mg/kg of body weight of pentobarbital. The renal arteries were
exposed by blunt dissection via a midline abdominal incision. The infrarenal
aorta and vena cava were cannulated with a 14-gauge angiocatheter (Introcan;
B. Braun, Melsungen, Germany). The supra- and infrarenal aorta and vena cava
were isolated from the general circulation by ligation, and the renal veins
were sectioned.
Tissue Analysis
The sections were examined by two experienced observers unaware of which
artery had been irradiated. The renal arteries and aortic local segments were
perfusion-fixed via a flexible aortic angiocatheter at a driving pressure of
100 mm Hg with neutral buffered 10% solution of formaldehyde (Sigma Chemical,
St. Louis, MO) for 60 min to fix expanded arteries in situ. The right kidney
was marked by a sagittal cut. Perirenal aorta, renal arteries, and kidneys
were then removed and immersion-fixed in the same formaldehyde fixative. The
rabbits were killed by exsanguination at the suprarenal aorta.
Tissue harvesting and preparation.—In harvesting the tissue, we used an embedding technique. Each renal artery was cut into seven (right artery) or eight (left artery) 3- to 4-mm-long segments. An aorta-sided ink label indicated the proximal pole of the sample. Another similar baseline landmark represented the distal extremity of each segment. Each identified lesion of the renal artery was therefore localized by its distance in millimeters from the ostium. Four-micrometer-thick serial sections of renal artery were sampled transversely (one series of eight slices per 250-µm-long portion of each artery) and dehydrated in graded ethanol. Among the slices, 40 per renal artery represented the segment close to the middle of the balloon (i.e., the wire), and two represented the reference segment. Twenty slices and one reference segment were stained with H and E and safran for histologic study, and another 20 slices and one reference segment were stained with orcein for histomorphometric analysis. Each specimen was evaluated for the presence of neointimal formation, medial dissection, alteration of the internal and external elastic laminae, and morphologic appearance of the adventitial, medial, and neointimal layers. Sections were also evaluated for the presence of intraluminal thrombus, intraluminal hemorrhage, and inflammatory cells.
Histomorphometry.—Reference and stenotic segments of the irradiated and nonirradiated renal arteries were examined. Neointima was defined as any tissue layer circumscribed by the internal elastic lamina, excluding intramural deposits of fibrin as well as larger, organized mural thrombotic material. Other specific changes were defined as the reshaping of the medial layer, tearing of one of the elastic laminae, and the presence of adventitial fibrosis.
All transverse sections were digitized via a CCD video camera (Cohu, San Diego, CA) and then morphometrically analyzed. In each artery, measurements were performed in the proximal healthy reference slice and in 20 stenosed slices (Fig. 2). The extent of restenosis was determined as the percentage of area of restenosis that is eaual to 100% x (1 - stenosis lumen area/reference segment lumen area).
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Data Processing
Renal artery restenosis was estimated by morphometric data, expressed as
mean ± standard error of the mean. The one-way analysis of variance
test was used to test for an overall treatment effect. We applied Wilcoxon's
signed rank test assuming abnormal distribution between the comparative data
after assessment of overall treatment effect. A p value less than
0.05 was required to reject the null hypothesis at the 95% confidence level.
Statistical analysis was performed with StatView software (4.5 version; Abacus
Concepts, Berkeley, CA).
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Group Characteristics
Among the five rabbits in group C, two received a left-sided and three, a
right-sided dummy wire, representing 10 control renal arteries. One rabbit was
irradiated bilaterally. The total number of nonirradiated renal arteries for
all three groups was 25; these arteries composed the overall control artery
group. The overall rate of thrombosis after percutaneous transluminal renal
angioplasty was not significantly different (p > 0.05) between the
irradiated (n = 2, 11.7%) and control (n = 3, 12%) arteries.
Fifteen irradiated and 22 nonirradiated patent arteries were available for
morphometric analysis. Data are displayed in
Table 1.
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Histologic Data
The right renal artery had a length of 30 ± 4 mm (mean ± SD),
and the left renal artery had a length of 35 ± 4 mm. Forty-two renal
arteries were cut into a series of 4-µm-thick slices. A total of 882 slices
(20 slices + 1 reference segment x 42 renal arteries) of the portions
close to the middle of the balloon (i.e., the wire) were analyzed. A variable
degree of rupture of the internal elastic lamina and media was observed in
injured segments of both control and beta-particle irradiated arteries,
resulting in vessel wall irregularities. However, rupture of the internal
elastic lamina was observed in each studied segment as a marker of
overdilatation efficacy.
The presence or absence of the dummy wire induced no significant difference in histologic findings in control group arteries. Most sections of the dilated arteries (639/840, 76%) showed evidence of two or more fractures of the internal elastic lamina, with a variable mass of neointima associated with the various medial gaps. In irradiated arteries, the neointima was generally found to be a smooth thin tunic delineated by a thin fibrin layer with apparently moderately smooth muscle proliferation. In our model (one injury and one treatment by percutaneous transluminal renal angioplasty), the difference between nonirradiated and irradiated arteries relative to medial disorganization and adventitial fibrosis was not significant. When present, the cells of the neointima morphologically resembled cells in the control arteries.
Mural fibrinous deposits were observed in a small number of samples. Complete coverage of the luminal surface by a monolayer of endotheliallike cells was seen in all samples. Because the incidence of thrombosis did not differ between irradiated arteries and control arteries (p > 0.05), thrombosis was assumed to be unrelated to irradiation. Perivascular nerve fibers and adipose tissue appeared to be normal. The brachytherapy delivery system did not become wedged in the dilated renal arteries, so no ischemic renal damage was reported.
Morphometric Data
We evaluated 315 slices of irradiated arteries and 462 slices of
nonirradiated arteries. The neointimal area of beta-irradiated arteries was
much smaller than that of control arteries, with a few sections showing a
total absence of neointimal formation
(Table 2), whether the internal
elastic lamina on the analyzed slices was ruptured or not. Because the
measurements of the medial areas in one group did not differ significantly
from the other group, irradiation seemed to have no apparent effect on
preexisting remodeling.
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Radiation Protection
The duration of fluoroscopic exposure was 244 ± 82 sec. The duration
of wire exposure was 63 ± 20 sec outside the rabbit and 30 ± 18
sec inside the rabbit during the source placement.
The whole-body dose was negligible. The first operator is closer to the source than the second operator, which may explain the difference in thermoluminescent dosimetric measurements for the two operators. The doses measured at wrist and finger were also low (Table 3). The presence of low-energy gamma rays remained undetectable by thoracic dosimeters.
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Endovascular Radiation System
Performance of intraarterial brachytherapy to prevent postangioplastic
restenosis by inhibiting the neointimal formation response to arterial injury
has been described in coronary and iliofemoral arteries
[25,
26]. Because 198Au
is a relatively low-energy gamma-ray emitter and high-energy beta-ray emitter,
its use may allow brachytherapy to be safely performed in a regular
interventional radiology facility.
Most published studies have evaluated the action of irradiation on the neointima. A1-though the favorable effect of radiation treatment on remodeling was previously reported in a swine coronary model [27], our results confirm preventive efficacy of treatment targeted to neointimal growth. These data are presumably related to the difficulty of separating recent posttreatment remodeling of the media from the initial postinduction remodeling. In the only study performed in the carotid arteries of rabbits [28], the internal elastic lamina remained intact, and no medial remodeling effect was investigated. Several 192Ir or 90Y irradiation experiments have been recently reported, using after-loader techniques or hand-delivery ribbons [9, 29]. Like 90Y, the reference pure beta-ray emitter, 198Au has a half-life of just 2.7 days and seems to be attractive in terms of safety. Because gold has no known metabolic toxicity, it does not need to be covered, in contrast with yttrium or strontium that must be isolated from the organism by titanium [9]. Our pilot study data suggested that the mechanical properties of gold, such as flexibility, facilitate advancement of the substance into curved arteries. The nonferromagnetic properties of gold could also make this element suitable for MR-guided percutaneous transluminal renal angioplasty [30] and related endovascular brachytherapeutic procedures in the near future.
Choice of a Small Injury—Treatment Model
For rabbits in the weight range of those in our study, the average diameter
of a safe renal artery is 1.5 ± 0.2 mm
[17]. A 2.0 x 20 mm
balloon, therefore, induces an overdilatation of 33% (range, 20-50%). Under
these conditions, the internal elastic lamina is ruptured in each artery by
the induction procedure, but the fracture length is possibly shorter than the
luminal area recovered by neointimal growth
[13].
The irradiation protocol has to be followed by precise tissue harvesting. Highly accurate placement of the source into a 5-mm segment is achieved by carefully positioning the middle of the balloon and wire in the X-ray beam center of a small field of view. Irradiation efficacy is thus comparatively evaluated in the area of the middle of the wire, corresponding to the middle of the angioplasty balloon. In our study, the dilated portion of each renal artery was longer than the irradiated segment containing the delivery system to eliminate any risk of vessel obstruction. Although we knew that this technique was likely to spoil chances of further histomorphometric evaluation because of the edge effects it would produce, only the postirradiation evaluation of artery segments close to the middle region of the balloon (i.e., wire) were considered for morphometric analysis in this experimental study. In human clinical conditions, the likelihood is that having an irradiation device that is longer than the dilated portion could be helpful in eliminating this "candy wrapper" effect.
Because our model was developed to investigate a pure renal restenosis problem, our experimental results are relevant not to initial treatment but to restenosis after angioplasty or possibly after stenting. In fact, stenting may unfortunately be complicated by increased neointimal hyperplasia (an incidence rate of 20%). Although immunosuppressor-coated stents appear to be effective against short-term in-stent restenosis, endovascular brachytherapy seems to present favorable long-term outcome. Long-term studies are still required to validate stents coated with immunosuppressive substances [7].
Our model differs from a repeated-injury model previously developed using swine [31], the aim of which was to develop additional medial damage and marked intimal hyperplasia. In our study, the second percutaneous transluminal renal angioplasty performed was designed to be therapeutic rather than to create a second injury. However, our approach mimics clinical conditions: the response of a renal artery with preexisting deeper lesions of the arterial wall to recent therapeutic percutaneous transluminal renal angioplasty. The small diameter and thickness of the rabbit renal artery present fewer difficulties in terms of source centering than would be encountered in larger animals [9, 28].
Thrombosis was assessed at histology but was not angiographically detected either after the overdilatation—deendothelialization step of stenosis induction or after the therapeutic percutaneous transluminal renal angioplasty, although the presence of deendothelialized areas may constitute a risk factor for thrombosis. The goal of this study was to evaluate the impact of 198Au irradiation after restenosis of patent renal arteries rather than to determine the incidence of thrombosis in our irradiated restenosis model, so the thrombosed arteries were not included in our morphometric analysis. However, in a recent study using a porcine model, although the overall rate of thrombosis increased dose-dependently from 0 to 18 Gy, the area of thrombus also decreased with increasing radiation dose. The data analysis suggested that intravascular brachytherapy could induce nonocclusive thrombotic foci [32].
Why a Wire Instead of a Stent?
The difficulty with intravascular irradiation is that it requires dosimetry
and radioprotection. In the case of irradiation by stent, the duration of dose
delivery theoretically is unlimited. It has not been clearly established
whether permanent irradiation from a radio-active stent is damaging to the
reendothelialization process, an essential condition for stent patency
[33]. Moreover, stent
deployment may induce edge failure or a "geographic miss" by
barotrauma [34]. Thus, if
198Au were used in stent form for irradiation, its half-life of 2.7
days could be safe in terms of vascular patency. Conversely, in-stent
absorption caused by the reabsorption of charged beta particles by the
radiation source may be found to be a limitation of radioactive stents with
low radioactivity. Recent reports calculating dose distributions around
198Au stents have emphasized that careful consideration should be
given to the dramatic dose fall-off due to in-stent absorption when
determining the initial activity level
[11]. However, in vivo
experimental evaluation of 198Au stents is still required, and the
potential dose fall-off can be eliminated by use of temporary wires, the
initial activity of which is considerably higher than that of stents.
Radioprotection
Two-centimeter-thick lead screens were initially used, because
198Au is also a gammaray emitter. However, lead screens finally
were found to be unnecessary because the gamma radiation dose was assessed as
negligible. Surgical forceps were an essential part of operator safety because
they increased the source-to-operator distance as did the acrylic screens,
which increased the absorption of beta particles. Apart from providing all the
advantages of beta irradiation
[9,
13,
28], the use of a
198Au wire provides an operator dose lower than that delivered by
fluoroscopy. In our experience, the dose delivered by radioactive gold wire
(0.0183 mSv) at 30 cm represents 72% of the dose delivered by fluoroscopy.
Five procedures per day for an annual activity of 220 days would therefore
deliver a maximal annual dose of approximately 48 mSv to the first operator,
who is closer to the radiation source. The practical use of a predominantly
beta-ray-emitting source does not require a bunker as gammaray emitters with
high dose rates do. Gold-198 is actually a beta- and gamma-ray emitter with a
low-energy gamma-ray-emitting component. Its use as a high-dose-rate beta-ray
source in conventional catheterization facilities allows the irradiation dose
to be delivered in approximately 10 min.
Limitations
Even though the model mimics a renal stenotic artery feeding an ischemic
kidney [17], it remains an
incomplete treatment approach to such disease because of the variability of
responses among species to angioplasty, procedure-related complications, and
prevention methods. Nonatheromatous rabbits were used to test the efficacy of
endovascular brachytherapy in a mechanically induced single-parameter model
because intravascular radiotherapy has been shown to interfere with
cholesterol metabolism [35].
Although the morphology of the lesions created in the rabbits differs from
what is normally observed in human renal artery stenosis with regard to
cholesterol overload, this nonatherosclerotic model eliminates the potential
for heterogeneous dose distribution through calcified plaque. The difference
between irradiated and nonirradiated arteries was assessed with only a 25-Gy
dose delivered at a radial 2-mm depth in the irregular but thin walls of
rabbit renal arteries. If targeting of the adventitial layer—which is
the layer assumed to be responsible for late-stage constriction of the
arterial wall [36]—is
necessary in endovascular brachytherapy, no technical solution to improve
centering is likely to completely prevent asymmetrical irradiation of grossly
irregular artery tunics. Because of the small size of the artery, no centering
was necessary in our study to show an antirestenosis effect. Therefore,
initial activity should be adapted in human renal artery applications. The
maximal inflammation of the arterial wall is reached 3 weeks after
percutaneous transluminal renal angioplasty, so the end point we chose seems
to be a reasonable period from which to draw short-term conclusions. Further
studies should be planned to evaluate these experimental irradiated restenotic
lesions with long-term follow-up.
Conclusion
The main objective of our experimental study was to compare stenotic renal
arteries treated by percutaneous transluminal renal angioplasty and beta
irradiation and arteries treated by percutaneous transluminal renal
angioplasty alone. Our data show that 198Au endovascular
brachytherapy may offer a 33% reduction of renal artery restenosis in a rabbit
model under extremely safe conditions of radiation protection. If these
preliminary data could be extrapolated to, for example, patients with genetic
risk factors for restenosis
[37], renal artery
198Au endovascular brachytherapy would probably constitute an
attractive restenosis prevention technique.
Acknowledgments
We thank Claude L. Le Blanche for manufacturing the dummy wires; David
Halpern and Catherine Philippe of the Institut National de la Recherche
Agronomique and Dany Trouillet and Marc Valero of the Office de Protection
contre les Rayonnements Ionisants for assistance in radiation protection;
Christian Bourgeois and Jean-Pierre Albert of the Institut National de la
Recherche Agronomique for animal care; Sandrine Boucheteil, Suzette Freire,
Maryse Caster, and Eugenia Pereira for literature research; Fabienne Cheminant
for editorial assistance; Nathacha Trofleau and Alex Laurent for
organizational support; and Anthony Saul for manuscript revision.
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