Yttrium90 delivered via a centering catheter and afterloader, given both before and after stent implantation, inhibits neointima formation in porcine coronary arteries (original) (raw)
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Journal of Interventional Cardiology, 2007
Absorbable metallic stents (AMS) utilizing Mg alloy carry advantages over permanent metallic stents because of their potential to eliminate stent thrombosis, chronic inflammation, or artifacts with noninvasive imaging. These stents, however, are associated with a modest degree of late recoil and intimal hyperplasia. The aim of the study was to test whether adjunct vascular brachytherapy (VBT) compared to AMS alone can overcome these limitations. Methods: Juvenile domestic pig coronary arteries underwent implantation of either AMS (n = 11) with prior adjunct VBT utilizing Sr/Y-90 β source seeds, with a dose of 24 Gy at 2 mm from the source, or AMS alone (n = 11). At 28 days following intravascular ultrasound, vessels were harvested and analyzed by histomorphometry. Results: Intravascular ultrasound analysis indicated that at follow-up, though statistically not significant, lumen and stent areas in the segments deployed with AMS following radiation were larger than those deployed with AMS alone (3.94 ± 1.38 and 3.53 ± 1.75 vs. 2.99 ± 1.05 and 3.58 ± 1.48). Extrastent plaque and intrastent plaque areas in the same segments were smaller (2.76 ± 0.82 and 0.24 ± 0.47 vs. 3.25 ± 1.94 and 0.58 ± 0.81).
High-Dose Intracoronary Irradiation after De Novo Stent Implantation
Strahlentherapie und Onkologie, 2006
Purpose: This randomized study was designed to compare the efficacy of high-dose coronary β-radiation after intravascular ultrasound-(IVUS-)guided direct stenting with sham treatment in patients with de novo lesions. Patients and Methods: 32 patients were enrolled in the study protocol. Following angioplasty procedure, intracoronary brachytherapy was performed with the Novoste™ Beta-Cath System. The prescribed dose was 24 Gy referred to the lamina elastica externa. Quantitative coronary angiography and IVUS were performed to analyze the treated coronary vessel. Results: Angiographic results revealed a significantly smaller minimal lumen diameter compared with the postprocedural minimal lumen diameter within the stented segment (p = 0.004) in the nonirradiated group. The same significant result was observed in the injured segment of the nonirradiated patients (p = 0.011). The IVUS data revealed a significant increase of the plaque volume after 8 months in the nonirradiated group compared to the postprocedural value (irradiated 5.41 ± 8.83 mm 3 vs. nonirradiated 21.11 ± 16.08 mm 3 ; p = 0.001). Late luminal loss was significantly greater in the nonirradiated group (p = 0.004). The primary clinical endpoint (death, myocardial infarction, repeat target lesion revascularization, percutaneous revascularization, coronary artery bypass surgery) was reached by seven irradiated (33.3%) and four (18.2%) nonirradiated patients (p = 0.623). Late stent thrombosis was observed in one irradiated patient.
Catheterization and Cardiovascular Interventions, 2003
The present study examined the role of source-centering and geographical miss in vascular brachytherapy. After implantation of 13 mm long stents, 38 coronary arteries in 13 pigs were randomly assigned to centered brachytherapy (n ؍ 13), eccentric brachytherapy (n ؍ 13), or no radiation (n ؍ 12). Geographical miss was avoided by careful placement of a 27 mm 32 P -radiation source. Restenosis was quantified by angiography, histomorphometry, and intravascular ultrasound at 28 days. Source-centering led to a significant (P < 0.001) reduction of in-stent area stenosis (centered radiation, 12% ؎ 5%; eccentric radiation, 37% ؎ 21%; control arteries, 41% ؎ 13%). Despite 7 mm coverage of the edge segments, radiation was found to induce edge stenosis due to neointima formation and constrictive vascular remodeling. We conclude that centered radiation was superior to eccentric radiation in reducing in-stent luminal narrowing while radiation-induced edge stenosis was still observed despite extension of the radiation zone to 7 mm beyond the stent edges. Catheter Cardiovasc Interv 2003;60:247-257.
Journal of Interventional Cardiology, 1999
Background: Radioactive stents have been proposed as a means to prevent restenosis. The ideal radioisotope to deliver endovascular irradiation via a radioactive stent is unknown. Objectives: To evaluate the dose response effects of "high" dose rate irradiation delivered by a high energy, short half-life, beta-particle emitting "yttrium ("Y) radioactive stent on neointimal formation in a porcine coronary model of restenosis. Methods: Fijiy-two 0-16.0 pCi "Y radioactive stents were implanted in the coronary arteries of 19 swine. Stents were oversized 10% to 20% greater than the baseline angiographic lumen diameter. Afrer 28 days, quantitative histological analysis was completed to determine neointimal area and percent in-stent stenosis. Results: The mean vessel injury scores were similar for the control and each of the 'OY radioactive stent groups. Neointimal area correlated with vessel injury for the control (r = 0.54, P < 0.0001) stents. The percent in-stent stenosis was similar for the nonradioactive control and the 0.25, 0.5, 1.0, 1.252.0, 8.0, and 16.0 pCi "Y radioactive stents. The neointimal area was greater for the 4.0 pCi (3.95 _f I. 16 mm2) and 8.0 pCi (3.55 _f 1.09 mm2) ' O Y stents as compared with the nonradioactive control stents (2.40 f-1.12 mm2, P 5 0.03). The increased neointimal area for the 4.0 pCi 90Y stents resulted in significantly greaterpercent in-stent stenosis (55 5 12) versus control nonradioactive stents (36 _f 18, P < 0.05). Conclusions: A radioactive stent manufactured with the short half-life beta-particle emitting radioisotope 90Y, designed to deliver a higher dose rate at implant than a "P radioactive stent, is ineffective in reducing neointimal formation in the porcine coronary model of restenosis. Further study is required to define effective cumulative dose and dose rate delivery for radioactive stents.
Intracoronary Radiation for Prevention of Restenosis Dose Perturbations Caused by Stents
2000
Background—Intravascular irradiation with b-emitters has been proposed for inhibition of restenosis in coronary arteries after balloon angioplasty or stent implantation. Previous studies have shown the effectiveness of g-radiation to prevent recurrent restenosis, even in the presence of an implanted stent. The limited range of b-particles compared with g-radiation, however, opens the question of whether absorption and scattering of b-particles by
Intracoronary radiation with gamma wire inhibits recurrent in-stent restenosis
Cardiovascular Radiation Medicine, 2001
To study the safety and efficacy of intracoronary gamma radiation delivered via a new high-activity 192 Ir source wire for the treatment of in-stent restenosis. In-stent restenosis results from neointimal tissue proliferation especially in its diffused form and presents a therapeutic challenge. Gamma radiation has been shown to decrease neointima formation within stents in animal models and in initial clinical trials. A total of 26 patients with in-stent restenosis underwent successful intervention and was treated with open-label 192 Ir using a high-activity line source. The specific activity of the source wire was 372 51 mCi, and the dwell time was 10.8 1.9 min. Primary endpoints were freedom from death, myocardial infraction (MI), and repeat target lesion revascularization (TLR) at 6 months. Secondary endpoints included angiographic restenosis and intravascular ultrasound (IVUS) neointimal hyperplasia. Procedural success was high (96.2%), and in-hospital and 30-day complications were low with no deaths, MI, or requirement for repeat revascularization. At 6 months, event-free survival was 85%: one patient required repeat PTCA, one underwent bypass surgery, and two had an MI. Baseline lesion length measured 15.77 mm. Follow-up angiography was available in 21/25 (84%) patients. The binary restenosis rates were 19.0% (4/21) in-stent and 23.8% (5/21) in-lesion. Follow-up IVUS was available in 20/25 patients. There was no increase in intimal hyperplasia from postintervention to follow-up (3.11.8 vs. 3.41.8 mm 2 ; P = .32). Eight patients had a reduction of neointimal intimal tissue at follow-up. These results indicate that intracoronary gamma radiation with the Angiorad source wire is safe and effective in preventing instent restenosis. D
International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: Intracoronary radiation has shown the potential to inhibit neointimal proliferation in porcine models of restenosis. The objective of this study was to determine whether intracoronary radiation using a new coiled wire of tungsten-188 ( 188 W), a pure  emitter (half-life 69.4 days) is safe. In addition, a dose of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and delivered intraluminally is sufficient to prevent restenosis and free from adverse effects. Methods and Materials: Ten domestic swine underwent 13-mm stent implantation (SI) into two arteries, left anterior descending plus either the left circumflex or right coronary artery. After SI, a closed-end lumen radiation catheter was inserted to the treated artery and a 40-mm coiled 188 W source was manually delivered to cover the stented segment and its margins. A total of 20 arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy delivered to 2 mm depth from the center of the source. Four weeks after the procedure, the swine underwent angiography and intravascular ultrasound using automated pullback at 0.5 mm/s. before being killed and the arteries perfusion fixed. Histopathologic and histomorphometric analyses were performed at 28 days after injury and radiation. Results: Irradiation with 188 W at a dose of 25 Gy after SI significantly inhibited neointima formation (intimal area: 1.05 ؎ 0.64 vs. 2.75 ؎ 0.99 mm 2 , p < 0.01) and at an 18 Gy dose of radiation (intimal area: 1.73 ؎ 0.49 vs. 2.75 ؎ 0.99 mm 2 ), as compared to controls. One artery receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow-up due to thrombus formation but no edge stenosis was observed in any of the irradiated arteries. Conclusions: Intracoronary radiation therapy using a new coiled wire of 188 W source delivered after SI appeared to be safe and well tolerated. The radiation doses demonstrated efficacy in reducing neointima formation in the porcine coronary stent injury model. © 2002 Elsevier Science Inc.
Fuel and Energy Abstracts, 2000
Purpose: Long-term preclinical studies using continuous, low-dose-rate vascular brachytherapy with 32 P -emitting stents have yielded largely disappointing results. In contrast, a shorter half-life, higher dose-rate 90 Y -emitting stent more closely mimics the delivery dose rate characteristics of clinically effective and ␥-wire and balloon brachytherapy devices. We evaluated the dose response characteristics of a 90 Y -emitting stent in the canine coronary injury model and hypothesized that this device would reduce neointimal formation. Methods: Seventy-seven 90 Y -emitting coronary stents (15 mm BXTM, 3.0-and 3.5-mm diameter) were implanted in 26 normal dogs (20 -25 kg) using a randomized, blinded study design. Stent activity included nonradioactive controls (n ؍ 24), 4.5 Ci (n ؍ 15), 8 Ci (n ؍ 12), 16 Ci (n ؍ 18), and 32 Ci (n ؍ 8). Histologic endpoints were assessed at 3 months. Results: Luminal stenosis and neointimal area were similar in control stents and low-activity (4.5 and 8 Ci) 90 Y stents. Higher activity stents (16 and 32 Ci) were associated with significant adverse effects. Frequent total occlusions (5 of 18 stents, 28%; p ؍ 0.008) and a 40% increase in neointimal area (p ؍ 0.024 vs. control) occurred in the 16 Ci group. Incomplete neointimal healing and a trend for reduced neointimal cell density were evident only in the 16-and 32-Ci group. Conclusion: Despite unique characteristics (2.7 day half-life and a higher dose rate) of 90 Y -emitting coronary stents, they have an adverse effect on neointimal formation, including frequent total occlusions at high activity levels. Incomplete healing, present 90 days (33 half-lives) after stent placement, indicates prolonged recovery from radiation injury.