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Histomorphometric Evaluation of ¹⁹⁸Au Endovascular Brachytherapy in a Renal Artery Restenosis Model in Rabbits

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.

OBJECTIVE. The main mid-term complication of percutaneous transluminal angioplasty of the renal artery is restenosis, which occurs in up to 50% of patients. Although no pharmacologic agent to date has been effective in preventing restenosis, both beta-ray emitters and gamma-ray emitters used in endovascular brachytherapy have been shown to reduce coronary restenosis. The objectives of this study were to evaluate the efficacy of ¹⁹⁸Au endovascular brachytherapy in preventing restenosis after percutaneous transluminal renal angioplasty and to determine the radiation dose to the operator.

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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