¹⁸⁶Re labeled stents for prophylaxis of restenosis: First animal results

OBJECTIVES: Restenosis is a major problem occuring after angioplasty, atherectomy and implantation of stents. It has been shown, that external beam teletherapy (X-rays) and intravascular brachytherapy (e.g. ¹⁹²Iridium ribbon seeds, ¹⁸⁸Re filled catheters, P-32-coated stents) prevents restenosis by inhibition of the proliferation of medial smooth muscle cells. The aim of this study was to investigate the potential of ¹⁸⁶Rhenium labeled stents to prevent restenosis in an animal model.

METHODS: New Zealand White rabbits were fed a 0.5% cholesterol diet four weeks prior to intervention. ¹⁸⁶Re (T = 3.8 d) labeled Palmaz-stents with an activity of 25.6 ± 2.5 MBq (n = 11) were placed in the infrarenal aorta of rabbits after balloon denudation. Animals with implanted unlabeled stents served as controls (n = 11). Whole body scintigrams were obtained after 1, 4, 24 hours and after 7 and 14 days to determine the bleaching of ¹⁸⁶Re from the stents in vivo. Seven weeks later, the animals were sacrified and morphometry and immunohistology was performed.

RESULTS: More than 80% of the ¹⁸⁶Re remained on the stent 14 days after implantation as determined by ROI analysis of the scintigrams. The neointimal area inducted seven weeks after implantation of the unlabeled stents was 2.2 ± 0.2 mm². No neointima was detectable in the aorta of animals with implanted radiolabeled stents. No intraluminal accumulation of fibrin and fibroblasts directly at the stent struts implies that the delivered dose can even be reduced.

CONCLUSION: Arterial implantation of ¹⁸⁶Re labeled stents was feasible and stable in vivo. The activity of 25.6 ± 2.5 MBq totally inhibited neointimal formation. In further studies we will reduce the stent activity in order to determine the therapeutic window of ¹⁸⁶Re labeled stents