Pure β-ParticleEmitting Stents Inhibit Neointima Formation in Rabbits

Author:

Hehrlein Christoph1,Stintz Marc1,Kinscherf Ralf1,Schlösser Klaus1,Huttel Ehrhard1,Friedrich Ludwig1,Fehsenfeld Peter1,Kübler Wolfgang1

Affiliation:

1. From the Department of Cardiology (C.H., M.S., W.K.) and the Department of Anatomy (R.K.), University of Heidelberg (Germany), and the Forschungszentrum Karlsruhe/Cyclotron Department (K.S., E.H., L.F., P.F.), Karlsruhe, Germany.

Abstract

Background Considerable experimental evidence exists that neointimal hyperplasia after angioplasty is inhibited by γ-irradiation of the treated arteries. A β-particle radiation is absorbed in tissue within a shorter distance away from the source than γ-radiation and may be more suitable for localized vessel irradiation. This study outlines a method to implant a β-particle–emitting radioisotope ( 32 P; half-life, 14.3 days) into metallic stents. The effects of these stents on the inhibition of neointimal hyperplasia was compared with conventional stents in a rabbit model. Methods and Results 32 P was produced by irradiation of red amorphous phophorus ( 31 P) with neutrons and was implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept apart from 31 P in a mass separator. The radioisotope was tightly fixed to the stents, and the ion implantation process did not alter the surface texture. Stent activity levels of 4 and 13 μCi were chosen for the study. Four and 12 weeks after placement of conventional stents and 32 P-implanted stents in rabbit iliac arteries, vascular injury and neointima formation were studied by histomorphometry. Immunostaining for smooth muscle cell (SMC) α-actin was performed to determine SMC cellularity in the neointima. SMCs were quantified by computer-assisted counting of α-actin immunoreactive cells. Endothelialization of the stents was evaluated by immunostaining for endothelial cell von Willebrand factor. No difference in vessel wall injury was found after placement of conventional and 32 P-implanted stents. Neointima formation was potently inhibited by 32 P-implanted stents only at an activity level of 13 μCi after 4 and 12 weeks. Neointimal SMC cellularity was reduced in 32 P-implanted stents compared with conventional stents. Radioactive stents were endothelialized after 4 weeks, but endothelialization was less dense than in conventional stents. Conclusions Neointima formation in rabbits is markedly suppressed by a β-particle–emitting stent incorporating the radioisotope 32 P. In this model, a dose-response relation with this type of radioactive stent was observed, indicating that a threshold radiation dose must be delivered to inhibit neointima formation after stent placement over the long term.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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