The Beta-Particle—Emitting Radioisotope Stent (Isostent): Animal Studies and Planned Clinical Trials
Section snippets
CONCEPT OF BETA-PARTICLE RADIOISOTOPE STENT
Rationale for intravascular irradiation: Despite the favorable lumen geometry created by stents, proliferating cells can migrate through these devices and lead to restenosis. Radiation is an appealing concept for preventing neointimal hyperplasia because it nonselectively kills dividing cells, whether they are malignant or benign. In addition, radiation has been shown to prevent keloid formation, which in many ways is similar to restenosis in that it results from the finite proliferation (in
ARTERIAL EFFECTS OF RADIOISOTOPE STENTING
Fig. 1 shows a human coronary artery 7 months after stent implantation. In this case, stents had been used as a palliative treatment prior to retransplantation. Thus, we were able to examine a series of Palmaz-Schatz stents (Johnson & Johnson Interventional Systems, Warren, NJ) at 3 weeks, 3 months, and 7 months following implantation in human coronary arteries. Despite relatively modest injury, with virtually no wires through the internal elastic lamina, there is a profound neointimal
INHIBITION OF NEOINTIMAL HYPERPLASIA: POTENTIAL MECHANISMS
We believe that the inhibition of neointimal proliferation seen with very-low-activity stents (0.1–1.0 μCi) may be caused in large part by the thinning of the proliferating smooth muscle cell population as these cells pass through the “electron fence” at the plane of the stent wires. In addition, there is evidence that very low levels of beta-particle irradiation may inhibit smooth muscle cell migration. At low activity levels (3–25 μCi)—although not ultra-low doses, such as those we have used
SAFETY FEATURES OF RADIOISOTOPE STENTS
Since essentially no radiation is delivered beyond the adventitia owing to the rapid drop-off in beta-particle emission, the use of radioisotope stents should be safe. The total body dose to the patient is <1/10,000 of the fluoroscopy dose scatter delivered during routine angioplasty. Prior to implantation, the stent is encased in a lucite/plastic shield, which blocks the electrons and protects the interventionalist from exposure to any measurable radiation.
Since the beta particles are
CLINICAL TRIAL
Finally, we are planning a clinical trial, the Isostent for Restenosis Intervention Study (IRIS), to begin in the summer of 1996. Our proposed plan for phase 1 is an initial trial involving 3 centers and 30 patients using a 1-μCi Palmaz-Schatz stent. In phase 2, we expect to enroll approximately 1,200 patients in a randomized, controlled, triple-blind (to patient, physician, and core labs) trial. This trial will likely include a larger dose/activity range and will compare clinical,
CONCLUSIONS
Based on in vitro studies, very-low-dose beta-particle irradiation emitted from a stent wire appears to inhibit vascular smooth muscle cell growth and/or migration. Endothelial cells, in contrast, appear relatively radioresistant. In vivo studies in porcine iliac and coronary vessels and rabbit iliac vessels have demonstrated marked, dose-dependent inhibition of neointimal hyperplasia after placement of radioisotope (32P) stents. We continue to conduct in vivo testing, looking at dose-response
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Low-dose radioactive endovascular stents prevent smooth muscle cell proliferation and neointimal hyperplasia in rabbits
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2009, Journal of Vascular and Interventional RadiologyCitation Excerpt :To demonstrate a clinically significant difference between the 2 treatments, CREST will require at least 2500 patients, excluding comparison between various clinical subgroups (eg, recurrent stenosis), for which an even greater number will be required. Potential areas of innovation include methods of providing cerebral protection using intravascular filters or balloons; smaller-diameter, more flexible, and hence less traumatic delivery systems; lowering rates of restenosis secondary to intimal hyperplasia by using local catheter brachytherapy; radiation-emitting stents (132–134); or biologically active coatings (135) and improved adjuvant pharmacological regimes using antiplatelet agents such as the glycoprotein IIb/IIIa inhibitors, which could potentially reduce the incidence of acute thromboembolism and improve long-term patency (136). This genuine potential for future improvement has prompted some authors to suggest a direct comparison with carotid endarterectomy may be premature (46,137–139).
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