A Beta-Particle Emitting Radioisotope Stent for the Prevention of Restenosis.

as a means for catheter–based coronary revascularization has rapidly changed the face of interventional cardiology. At many leading centers, 60-70% of all percutaneous coronary interventions now utilize stenting. The relatively rapid acceptance and increasingly widespread use of stents has been driven by an improvement in the predictability of intervention with lessened acute and subacute closure, and convincing randomized data (at least with the Palmaz–Schatz stent) of improved intermediate and long–term clinical outcomes.1 3 Although stenting has clearly made a substantial impact in improving the restenosis problem after angioplasty, in stent restenosis remains a problem particularly after stenting longer lesions, smaller vessels, ostial lesions and saphenous vein grafts. In these subsets clinically important restenosis still occurs in 25-45%. This paper will address the rationale, development, i n vitro and in vivo data relevant to the development of a beta–particle (electron) emitting radioisotope stent intended to further decrease restenosis after stenting. Mechanism of Restenosis: Stenting versus Balloon Angioplasty. Figure 1 shows a photomicrograph of a Palmaz–Schatz stent 7 months after implantation in the left circumflex coronary artery of a cardiac transplant patient with accelerated transplant atherosclerosis. The patient received a second heart transplant, and we were able to examine the stented segment. One can appreciate a tremendous volume of neointimal hyperplasia within the lumen, inside the stent. The stent remains well expanded, without evidence of extrinsic stent compression. This finding is consistent with recently presented intravascular ultrasound data4 following human coronary stent implantation. This picture contrasts with the recent IVUS data regarding the mechanisms of restenosis after balloon angioplasty and directional atherectomy.5 , 6 In those patients it is becoming increasingly clear that a substantial proportion of late luminal loss is due to late constriction (“unfavorable remodeling”) of the treated segment, with a more modest contribution from neointimal hyperplasia. Thus, the impact of stents upon improved long–term outcome is in large part related to the scaffolding effect of the stent which prevents late constriction of the segment. Interestingly, late loss secondary to neointimal hyperplasia appears to be significantly increased after stenting as compared to balloon angioplasty alone.2 This important observation leads one to the logical next step in the prevention of restenosis; namely the A Beta–Particle Emitting Radioisotope Stent for the Prevention of Restenosis