phosphorus-radioisotopes and Coronary-Restenosis

Based on therapeutic approach for benign diseases, vascular brachytherapy decreases smooth vascular muscle cells proliferation and multiplication which lead to the formation of the neo-intima. The radioactive positive action affects arterial recoil due to post angioplasty vessel injury. Randomised studies has shown good angiographic results up to 6 months of follow-up, with 50% in-stent restenosis rate decrease and on the analysed segment as well. Decrease on Mace and TLR show statistically significance. Results don't correlate with emitter and bêta emitters had been introduced in France recently. Vascular brachytherapy is actually indicated for in-stent restenosis, there is no evidence to perform this treatment for de novo lesion. Geographic miss, source centering, late thrombosis and pullback procedure may interfere with treatment quality. IVUS allows best target volume determination to a higher quality level. Internationals guidelines such as Eva-Gec-Estro recommendations could increase treatment safety and enable development of an optimal technique.

Topics: Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; France; Gamma Rays; Half-Life; Humans; Iridium Radioisotopes; Multicenter Studies as Topic; Phosphorus Radioisotopes; Radiopharmaceuticals; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

The implantation of radioactive stents was the first procedure of a coronary brachytherapy in Europe examined in multicenter clinical trials.. After more than 400 patients with radioactive stents were analyzed, it became clear that overall restenosis rates were not reduced. A new phenomenon called the "edge effect" or "candy-wrapper" effect was discovered, which later was also described for catheter-based brachytherapy. Currently, the implantation of radioactive stents for the prevention of restenosis cannot be recommended.. Although technical improvements of radioactive stents are theoretically possible, novel drug coated stents may overcome any future research of stent-based radiotherapy. Drug eluting stents induce antiproliferative effects beyond the stent margins. Edge effects were not observed in preliminary trials. However, long-term results need to be awaited.

Topics: Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Brachytherapy; Coronary Angiography; Coronary Restenosis; Humans; Immunosuppressive Agents; Phosphorus Radioisotopes; Pilot Projects; Randomized Controlled Trials as Topic; Sirolimus; Stainless Steel; Stents

We sought to assess the efficacy of vascular brachytherapy (VBT) combined with stenting for the primary prevention of restenosis.. Intravascular brachytherapy after stent implantation for de novo lesions has been abandoned for the present. We revisited this procedure by optimizing all procedural steps-the use of glycoprotein IIb/IIa blockers, direct stenting, adequate radiation coverage, avoidance of edge damage, source centering, intravascular ultrasound-guided dosimetry, and continuation of a dual anti-platelet regimen for one year.. The Beta-Radiation Investigation with Direct stenting and Galileo in Europe (BRIDGE) study is a multicenter, randomized controlled trial evaluating the long-term efficacy of VBT with P-32 (20 Gy at 1 mm in the coronary wall) after direct stenting. The primary end point was angiographic intra-stent late loss; secondary end points were six months binary restenosis and neo-intimal hyperplasia. Patients (n = 112) with de novo lesions (2.5 to 4.0 mm in diameter up to 15 mm long) were randomized to either VBT or no-VBT.. At six months, intra-stent loss was 0.43 and 0.84 mm (p < 0.001) in the irradiated and control groups, respectively. Intra-stent neo-intimal volume was reduced from 36 mm3 to 10 mm3. However, in the irradiated group there were six late occlusions as well as eight restenoses outside the stented and peri-stented area at the fall-off dose edges of the irradiated area. Accordingly, the target vessel revascularization and major adverse cardiac and cerebrovascular events rates at one year in the VBT group (20.4% and 25.9%, respectively) were higher than in the control group (12.1% and 17.2%, respectively).. Despite the optimization of pre-, peri-, and post-procedural factors and despite the relative efficacy of the brachytherapy for the prevention of the intra-stent neo-intimal hyperplasia, the clinical outcome of the irradiated group was less favorable than that of the control group.

Topics: Aged; Aspirin; Brachytherapy; Clopidogrel; Coronary Angiography; Coronary Restenosis; Europe; Female; Humans; Hyperplasia; Male; Middle Aged; Phosphorus Radioisotopes; Platelet Aggregation Inhibitors; Primary Prevention; Radiation Dosage; Stents; Ticlopidine; Tunica Intima; Ultrasonography, Interventional

Topics: Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Humans; Logistic Models; Phosphorus Radioisotopes; Stents; Treatment Outcome

In-stent restenosis is a major limitation of intracoronary stenting. Ionising gamma radiation has been shown to reduce recurrence of restenosis after stent placement. We aimed to compare the effects of intracoronary beta radiation treatment with those of placebo for clinical and angiographic outcomes of patients with diffuse in-stent restenosis.. 332 patients with in-stent restenosis underwent successful coronary intervention, and were then randomly allocated to intracoronary beta radiation with a phosphorus-32 source (n=166) or placebo (166) delivered into a centreing balloon catheter through an automatic afterloader. Longer lesions (>22 mm of dilated length) were treated with tandem positioning of the study wire. The primary safety endpoint was major adverse cardiac events, defined as death, myocardial infarction, and repeat target-lesion revascularisation at 9 months. The primary efficacy endpoint was binary angiographic restenosis rate in the analysis segment during 9-months' follow-up. Analysis was by intention to treat.. Procedural success, and in-hospital and 30-day complications were similar among the two groups. 24 (15%) patients in the radiated group had the primary safety endpoint of death, myocardial infarction, or repeat target-lesion revascularisation over 290 days compared with 51 [corrected] (31%) in the placebo group (difference 16% [95% CI 7-25], p = 0.0006). Binary angiographic restenosis rate was lower in the radiated group than the placebo group for the entire analysed segment (difference 25% [14--37], p < 0.0001).. Vascular brachytherapy using pure beta-emitter 32P delivered into a centreing catheter via an automatic afterloader can be used to reduce overall revascularisation in patients undergoing treatment for diffuse in-stent restenosis.

Topics: Brachytherapy; Coronary Restenosis; Electrocardiography; Endpoint Determination; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Stents; Treatment Outcome

This article investigates the dosimetry of a radioactive stent and radioactive liquid balloon placed into the heart vasculature to prevent restenosis after atherosclerosis treatment. The research aims to know the dosages to establish a suitable activity which achieves restenosis control and thereafter minimize radiation effects in the cardiac muscle. In order to accomplish the dosimetric analysis, a heart voxel model was assembled based on tomographic images. The computational model consists of a three-dimensional matrix taken from 60 tomographic images representing the major heart tissues. A radioactive ¹⁵³Sm liquid balloon is simulated as well as a ³²P radioactive stent, inserted in an arbitrary heart artery. After simulation processing, the absorbed dose rate was evaluated in the heart musculature. The models are presented in two- and three-dimensional previews and the dosage profiles are shown by isodose curves superimposed onto the heart model.

Topics: Angioplasty; Brachytherapy; Computer Simulation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Humans; Imaging, Three-Dimensional; Models, Cardiovascular; Phosphorus Radioisotopes; Prosthesis Design; Radiation Dosage; Radiation Injuries; Radiographic Image Interpretation, Computer-Assisted; Radioisotopes; Radiotherapy, Computer-Assisted; Samarium; Stents; Tomography, X-Ray Computed

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents/RSs/ n = 16, bare-metal stents/BMSs/ n = 43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 +/- 20.1% vs. 27.6 +/- 22.0%, p = 0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p = 0.022), plasminogen activator inhibitor-1 (PAI-1, p = 0.047), tissue-type plasminogen activator (tPA, p = 0.047) and CD40 ligand (CD40L, p = 0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with high-grade restenosis at the follow up.

Topics: Aged; CD40 Ligand; Chemokines; Chemokines, CXC; Coronary Restenosis; Coronary Stenosis; Female; Humans; Inflammation Mediators; Male; Middle Aged; Phosphorus Radioisotopes; Plasminogen Activator Inhibitor 1; Prognosis; Prospective Studies; Stents; Thrombosis; Time Factors; Tissue Plasminogen Activator

The intracoronary changes that occur after brachytherapy for in-stent restenosis (ISR) have yet to be fully established. The purpose of this study in patients who had ISR was to examine the serial angioscopic changes in intracoronary lesions that occurred after brachytherapy. Forty-four patients who had ISR (49 lesions) underwent balloon angioplasty (n = 34) or directional atherectomy (n = 15), followed by intracoronary brachytherapy using a beta-emitting phosphorus-32 source wire. Angioscopic investigations were performed 3 and 9 months after brachytherapy. Uncovered stents were detected in 63.3% of lesions at 3 months. A significant decrease (p = 0.028) in this prevalence occurred over the next 6 months, with 36% of lesions having uncovered stents at 9 months. At 3 months, 33% of the lesions had visible erosion or ulceration and superficial thrombus. The prevalence of these characteristics was decreased at 9 months, although 17% of the lesions were still ulcerated or eroded at that time. Protruding thrombus was not observed in any lesion at 3 and 9 months. In conclusion, uncovered stents and intimal erosions or ulcerations were still present 9 months after brachytherapy in 36% and 17% of lesions, respectively. These results suggest that the healing process was not completed 9 months after brachytherapy in approximately 33% of lesions.

Topics: Aged; Angioplasty, Balloon; Angioscopy; Atherectomy, Coronary; Brachytherapy; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Female; Follow-Up Studies; Humans; Male; Phosphorus Radioisotopes; Stents; Tunica Intima

It is unknown whether model of renarrowing after beta-radiation for in-stent restenosis (ISR) is influenced by the type of geographic miss (GM).. In 166 ISR treated with Galileo, serial quantitative coronary angiographic analysis was done. Minimal lumen diameters and lengths were measured for (1) stent, (2) peri-stent subsegments subjected to angioplasty with/without irradiation, and (3) irradiation margins. GM was defined as: (Type 1) edge injury within the 32P source dose fall-off: 2.0 mm inside and outside the source end marker or (Type 2) overt, nonirradiated injury: beyond the outer 2.0-mm long dose fall-off zone.. Restenosis rate was 28.3% at 8.9+/-4.5 months with 60% located exclusively outside the stent. Type 1 GM was present in 24.7% of proximal edges, whereas Type 2 in 18.1%. Respective percentages for distal edges were 23.5% and 15.7%. Regardless of presence and type of GM, significant late lumen loss occurred only outside the stent. However, the biggest late lumen loss at the proximal edge was induced by the Type 1 GM (0.65+/-0.79, p<0.001), while proximal Type 2 GM was not associated with edge renarrowing (-0.04+/-0.48, p=NS). Both reference lumen diameter and proximal Type 1 GM influenced restenosis independently (OR 0.47; 95%CI 0.24-0.90; p=0.023 and OR 2.46; 95%CI 1.12-5.40; p=0.025).. Regardless of presence and type of geographic miss, late lumen loss after beta-radiation occurs only outside the stent. However, injury within the proximal 32P dose fall-off but not overt edge injury is associated with the biggest late lumen loss at the respective edge, triggering recurrent restenosis.

Topics: Aged; Beta Particles; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Dose-Response Relationship, Radiation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Predictive Value of Tests; Radiotherapy Dosage; Stents; Treatment Outcome

Intravascular brachytherapy has been adopted for the indication of in-stent restenosis on the basis of results of clinical trials using mainly stainless steel stents. Recently, a new stent made of cobalt-chromium L-605 alloy (CoCr, p=9.22 g/cm3) (MULTI-LINK VISION) was introduced as an alternative to the 316L stainless steel stent design (SS, p=7.87 g/cm3) (MULTI-LINK PENTA). In this work, we used the Monte Carlo code MCNPX to compare the dose distribution for the 32P GALILEO source in CoCr and SS 8 mm stent models. The dose perturbation factor (DPF), defined as the ratio of the dose in water with the presence of a stent to the dose without a stent, was used to compare results. Both stent designs were virtually expanded to diameters of 2.0, 3.0, and 4.0 mm using finite element models. The complicated strut shapes of both the CoCr and SS stents were simplified using circular rings with an effective width to yield a metal-to-tissue ratio identical to that of the actual stents. The mean DPF at a 1 mm tissue depth, over the entire stented length of 8 mm, was 0.935 for the CoCr stent and 0.911 for the SS stent. The mean DPF at the intima (0.05 mm radial distance from the strut outer surface), over the entire stented length of 8 mm, was 0.950 for CoCr, and 0.926 for SS. The maximum DPFs directly behind the CoCr and SS struts were 0.689 and 0.644, respectively. All DPF estimates have a standard deviation of +/-0.6%(k=2), approximating the 95% confidence interval. Although the CoCr stent has a higher effective atomic number and greater density than the SS stent, the DPFs for the two stents are similar, probably because the metal-to-tissue ratio and strut thickness of the CoCr stent are lower than those of the SS stent.

Topics: Brachytherapy; Chromium; Cobalt; Coronary Disease; Coronary Restenosis; Humans; Monte Carlo Method; Phosphorus Radioisotopes; Radiometry; Software; Time Factors

Treatment of in-stent restenosis after implantation of a drug-eluting stent is a critical issue. We provide the first report of the use of intravascular radiation therapy for this purpose in a 73-year-old diabetic patient stented for small-vessel bifurcation; treatment of Cypher diffuse in-stent restenosis with (32)P brachytherapy proved successful at clinical and angiographic follow-up at 7 months. This finding should encourage systematic studies on the safety and efficacy of IRT in this problematic setting.

Topics: Aged; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Follow-Up Studies; Humans; Male; Myocardial Infarction; Phosphorus Radioisotopes; Prosthesis Failure; Stents

Accurate patient-specific dosimetry in intravascular brachytherapy (IVBT) is generally difficult due to the extremely high-dose gradient, complexity of treatment device, and patient-specific geometry (e.g., calcification, stent, curvature, movement of target). The purpose of this study is to analyze quantitatively and systematically the dose effects of calcification, stent, guidewire, and source curvature on clinical dosimetry in an IVBT procedure, and propose a method that can be used to assess these effects in routine clinical practice.. Monte Carlo techniques were used to calculate 3-D dose distribution in both homogeneous and inhomogeneous media for three most commonly used IVBT sources: (90)Sr beta (Novoste), (192)Ir gamma (Cordis/Best), and (32)P beta (Guidant). Dosimetric perturbations in the presence of metallic stents, calcified plaques, metallic guide wires, and source curvature were studied for situations commonly encountered in the clinic. The importance of each of these perturbations and their practical influence on patient-specific dosimetry were analyzed. Factors (plaque, stent, guidewire, and curvature) that may be used to correct/reduce these perturbations were introduced to prevent dosimetric cold spots during IVBT. Practical methods of using these correction factors are proposed.. Dose perturbations are significant due to the presence of source curvature, metallic stents, calcified plaques, and metallic guide wires, especially for beta sources. These perturbations can be as high as 30% under normal clinical conditions, although they can be much higher in extreme situations. Empirical relationships of plaque factor with the thickness of calcified plaque, stent factor with stent metallic surface area, guidewire with guidewire thickness, and curvature factor with the bending angle are derived. These relationships are found to be useful in improving clinical dose accuracy in IVBT treatment planning or dose evaluation after treatment.. Significant dose perturbations due to the presence of source curvature, metallic stents, calcified plaques, and guide wires have been found in IVBT for in-stent restenosis. Because it has been reported that, with the current prescriptions for IVBT, higher doses consistently improve treatment outcomes, the empirical method derived from this work can be used to assess cold spots dosimetrically, thus improving patient-specific dosimetry for IVBT.

Topics: Blood Vessel Prosthesis Implantation; Brachytherapy; Calcinosis; Combined Modality Therapy; Coronary Restenosis; Dose Fractionation, Radiation; Equipment Design; Humans; Iridium Radioisotopes; Monte Carlo Method; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Stents; Strontium Radioisotopes

Intracoronary brachytherapy after percutaneous transluminal coronary angioplasty (PTCA) is usually performed with catheter-based treatment techniques in a straight vessel segment. There is a growing interest for treatment of bifurcations, which requires consecutive positioning of the source in main vessel and side branch.. In-house developed software (IC-BT doseplan) is used to explore the optimal positioning of the source in modelled bifurcations with different shape for the source types available in our hospital, i.e. (90)Sr/(90)Y, (32)P and (192)Ir. The results were summarised in look-up tables. The usefulness of these look-up tables was tested on various clinical examples.. Tabulated results for the modelled bifurcations yield an estimation of the distance between the sources (gap width) in relation to the geometry and source type: (90)Sr/(90)Y gap range 3-8.5 mm, (32)P gap range 2-7 mm and (192)Ir gap range 3.5-8 mm. The average dose relative to 2 mm from the source axis is: (90)Sr/(90)Y, (mean+/-SD) 120+/-40%; (32)P, 125+/-50% and (192)Ir, 120+/-22%. The look-up tables also provide the coarse location and value of maximum and minimum dose: (90)Sr/(90)Y, 220-60%, (32)P, 230-55% and (192)Ir, 170-85%. It appeared that the look-up tables provide a good approximation of the optimal gap width in the clinical examples.. Tabulated optimal gap widths are very useful for quick estimation of the required gap width for a given bifurcation and source type, in case the prescribed dose in both vessels is the same. In unfavourable geometries there is a risk of local underdosage. Individual treatment planning using a program such as IC-BT doseplan is then recommended.

Topics: Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Restenosis; Coronary Vessels; Humans; Iridium Radioisotopes; Models, Biological; Phosphorus Radioisotopes; Radiotherapy Dosage; Strontium Radioisotopes; Yttrium Radioisotopes

The purpose of this analysis was to evaluate if overdosage during intracoronary irradiation due to overlapped source stepping may result in long-term morphologic changes in vessel anatomy.. Baseline angiograms of patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation with source stepping were analyzed. Overlapping was considered present for the segment with overlapped reference isodose length (RIL) (RIL = segment with > or = 90% of reference dose at 1 mm vessel wall depth). Baseline and 6-months follow-up volumetric intravascular ultrasound (IVUS) analysis were performed for the overlapped segment and for proximal and distal segments of equal length.. Overlapping was found in six patients (three patients: (32)P treatment; three patients: (90)Sr/Y treatment); final analysis was performed in four patients. Comparison of the baseline and follow-up IVUS volumetric parameters revealed no significant change in lumen or vessel volumes at segments of overlaps in comparison to proximal and distal reference segments.. Increased dosage due to overlapping during source stepping is not associated with morphologic changes in vessel anatomy at follow-up.

Topics: Angioplasty, Balloon; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Radiation; Humans; Imaging, Three-Dimensional; Phosphorus Radioisotopes; Prospective Studies; Strontium Radioisotopes; Ultrasonography, Interventional

The objective of this study was to determine the safety and efficacy of (32)P beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). (32)P beta-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR.

Topics: Aged; Beta Particles; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Phosphorus Radioisotopes; Prospective Studies; Radiopharmaceuticals; Stents; Time Factors; Treatment Outcome

The aim of this study was to compare 6-month clinical outcomes of patients with in-stent restenosis (ISR) involving the ostium treated with intracoronary radiation therapy (IRT) compared to placebo therapy, and also to nonostial lesions treated with IRT. Coronary interventions in ostial lesions have a high rate of recurrence of restenosis. The impact of IRT on ostial ISR has been inadequately characterized. We assessed patients enrolled in gamma (192-iridium) and beta (90-yttrium, 32-phosphorus) radiation trials for ISR at the Washington Hospital Center. Of patients receiving IRT, 105 (8%) patients had ostial ISR and 1,289 (92%) patients had nonostial ISR. Twenty-seven patients had ostial ISR and received placebo therapy. Baseline demographic and angiographic and procedural details were similar, except ostial IRT patients had a trend toward shorter lesions (15.4 +/- 10.8 vs. 24.1 +/- 12.2 mm; P < 0.001) and had a higher rate of saphenous vein graft disease (46% vs. 19%; P < 0.001) compared to nonostial IRT patients. At 6 months, ostial lesions treated with IRT for ISR had a reduced rate of target lesion revascularization (TLR) compared to ostial lesions treated with placebo (15% vs. 43%; P = 0.004). Outcomes at 6 months were similar for the ostial and nonostial IRT groups including TLR (15% vs. 14%; P = 0.80) and composite major adverse cardiac events (18% vs. 15%; P = 0.46). Intracoronary radiation therapy is effective for ostial in-stent restenotic lesions and should be comfortably used for this challenging anatomic location.

Topics: Aged; Brachytherapy; Coronary Restenosis; Female; Humans; Iridium Radioisotopes; Male; Middle Aged; Phosphorus Radioisotopes; Retrospective Studies; Treatment Outcome; Yttrium Radioisotopes

Intravascular brachytherapy (IVBT) has been recognized as a preferred treatment for coronary in-stent restenosis (ISR) in routine practice. Stents made of high-Z materials will inevitably perturb the dose distribution of IVBT. In this work, we have conducted a systematic study on these dose perturbations for three commercially available IVBT sources.. The EGSnrc Monte Carlo codes were used to calculate the dose distributions for the 90Sr, 32P, and 192Ir IVBT sources with and without a metallic stent in place. The ring stent type made of different material and with different strut size, metallic surface area (MSA), and radius was studied.. Calculations show that dose enhancement of 5% to 20% occurs inside stent in the region close to the stent struts (luminal side) for all three sources. In the region outside stent (adventitial side), dose reduction of 5% to 20% is observed for a beta source, whereas the dose effect is negligible for the gamma source. For a given stent design, the tantalum stent yields a larger dose effect than other stents made of steel, Ti, Ni, or nitinol. It is found that the dose effect significantly depends on strut thickness, and it is strongly correlated to MSA. The MSA may be used to characterize the dose effect of a stent. Sample empiric equations to relate the dose perturbations to MSA for a given source, a stent material, and a strut thickness were derived.. The dose perturbations due to the presence of metallic stents were found to be significant in IVBT for ISR. The dose effects of a stent can be estimated from its MSA based on derived empiric equations. The data presented are practically useful to consider the dose effects of stents in dose evaluation/treatment planning for using IVBT to treat ISR.

Topics: Brachytherapy; Coronary Restenosis; Equipment Design; Half-Life; Humans; Iridium Radioisotopes; Monte Carlo Method; Phosphorus Radioisotopes; Radiotherapy Dosage; Stents; Strontium Radioisotopes

Intravascular brachytherapy may cause "exaggerated" vessel remodeling with late incomplete apposition in segments that have little disease, which are exposed to higher radiation doses. The long-term clinical impact of this finding is unclear.

Topics: Aged; Brachytherapy; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Equipment Design; Equipment Failure; Female; Follow-Up Studies; Humans; Incidence; Linear Models; Male; Middle Aged; Phosphorus Radioisotopes; Risk Factors; Single-Blind Method; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The experimental dosimetry in a water phantom of a 32P linear source, 20 mm in length, used for the brachytherapy of coronary vessels is reported. The source content activity, A, was determined by means of a calibrated well ion-chamber and the value was compared with the contained activity reported in the manufacturer's certification. In this field of brachytherapy dosimetry, radiochromic film supplies a high enough spatial resolution. A highly sensitive radiochromic film, that presents only one active layer, was used in this work for the source dosimetry in a water phantom. The radiochromic film was characterized by electron beams produced by a clinical linac. A Monte Carlo calculation of beta spectra in water at different distances along the source transverse bisector axis allowed to take into account the low dependence of film response from the electron beam energy. The adopted experimental set-up, with the source in its catheter positioned on the film plane inside the water phantom, supplies accurate dosimetric information. The measured dose rate to water per unit of source activity at reference distance, D(r0, theta0)/A, in units of cGy s(-1) GBq(-1), was in agreement with the value reported in the manufacturer's certification within the experimental uncertainty. The radial dose function, g(r), is in good agreement with the literature data. The anisotropy function F(r, theta) is also reported. The analysis of the dose profile obtained at 2 mm from the source longitudinal axis shows that the uniformity is within 10% along 75% of the 20 mm treatment length. The adopted experimental set-up seems to be adequate for the quality control procedure of the dose homogeneity distribution in the water medium.

Topics: Algorithms; Brachytherapy; Calibration; Catheters, Indwelling; Coronary Restenosis; Europe; Film Dosimetry; Humans; Phosphorus Radioisotopes; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Reproducibility of Results; Sensitivity and Specificity

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 beta-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.

Topics: Animals; Arteries; Beta Particles; Blood Vessel Prosthesis Implantation; Brachytherapy; Cardiac Catheterization; Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Erythrocytes; Follow-Up Studies; Models, Cardiovascular; Myocytes, Smooth Muscle; Phosphorus Radioisotopes; Severity of Illness Index; Stents; Swine; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; Ventricular Remodeling

Topics: Animals; Arteries; Beta Particles; Brachytherapy; Cardiac Catheterization; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Humans; Phosphorus Radioisotopes; Stents; Ultrasonography, Interventional

Radiolabeled drug-eluting stents have been proposed recently as a novel method to potentially reduce restenosis in coronary arteries. A P-32 labeled oligonucleotide (ODN) loaded on a polymer coated stent is slowly released in the arterial wall to deliver a therapeutic dose to the target tissue. However, the relatively low proportion of drugs transferred to the arterial wall (<2%-5% typically) raises questions about the degree to which radiolabeled drugs eluted from the stent can contribute to the total radiation dose delivered to tissues. A three-dimensional diffusion-convection transport model is used to model the transport of a hydrophilic drug released from the surface of a stent to the arterial media. Large drug concentration gradients are observed near the stent struts giving rise to a nonuniform radiation activity distribution for the drug in the tissues as a function of time. A voxel-based kernel convolution method is used to calculate the radiation dose rate resulting from this activity build-up in the arterial wall based on the medical internal radiation dose formalism. Measured residence time for the P-32 ODN in the arterial wall and at the stent surface obtained from animal studies are used to normalize the results in terms of absolute dose to tissue. The results indicate that radiation due to drug eluted from the stent contributes only a small fraction of the total radiation delivered to the arterial wall, the main contribution coming from the activity that remains embedded in the stent coating. For hydrophilic compounds with rapid transit times in arterial tissue and minimal binding interactions, the activity build-up in the arterial wall contributes only a small fraction to the total dose delivered by the P-32 ODN stent. For these compounds, it is concluded that radiolabeled drug-eluting stent will not likely improve the performance of radioactive stents for the treatment of restenosis. Also, variability in the delivery efficacy of drug delivery devices makes accurate dosimetry difficult and the drug washout in the systemic circulatory system may yield an unnecessary activity build-up and dose to healthy organs.

Topics: Arteries; Constriction, Pathologic; Coronary Restenosis; Coronary Vessels; Diffusion; Heparin; Humans; Models, Statistical; Oligonucleotides; Phosphorus Radioisotopes; Polymers; Radiometry; Stents; Time Factors

Three radiation sources have been approved for commercial use in vascular brachytherapy. The beta sources ((90)Strontium and (32)Phosphorous) are more popular because of less radiation protection concerns than gamma sources. Because (90)Strontium has a longer half-life than (32)Phosphorous, it requires less frequent source exchanges. Also, because (90)Strontium is more penetrating, a similar benefit can be achieved with lower delivered doses. Based on these advantages, (90)Strontium is the preferred isotope for vascular brachytherapy.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Restenosis; Humans; Iridium Radioisotopes; Phosphorus Radioisotopes; Strontium Radioisotopes; Yttrium Radioisotopes

The aim of the study was to evaluate, on single center prospective data, long-term angiographic and clinical results of intracoronary beta (32P) brachytherapy in "real world" patients with high-risk in-stent restenosis lesions.. Sixty-nine consecutive patients (77 lesions) with high-risk in-stent restenosis (mean lesion length 30.3 +/- 16.1 mm, pattern III-IV 57.2%, diabetes 33.3%) treated with percutaneous dilation procedures and beta-radiation therapy, underwent 7-month clinical and angiographic follow-up.. One patient (1.4%) presented with procedural non-Q wave myocardial infarction. At a mean follow-up of 7 +/- 1.5 months, death was observed in 1 patient (1.4%) and non-Q wave myocardial infarction in 3 (4.3%) (in 2 patients, who prematurely discontinued antiplatelet therapy, caused by late coronary thrombosis). Seven-month binary angiographic restenosis occurred in 20 lesions (25.9%) (in-stent restenosis 11.6%). Target lesion and target vessel revascularization occurred in 20 (28.9%) and 21 (30.4%) patients. At follow-up only 12 (17.3%) patients presented with CCS class III-IV angina. After intracoronary beta brachytherapy angiographic restenosis occurred regardless of the vessel size, lesion length and ostial location. On the contrary a high restenosis rate was documented in obstructive lesions.. As applied in routine clinical practice, radiation therapy is safe and effective in the treatment of high-risk in-stent restenosis. In spite of all that, total occlusion at baseline predicts late angiographic restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Prospective Studies; Retrospective Studies; Stents

Studies of intravascular brachytherapy to prevent restenosis following angioplasty have shown many promising results. Accurate dose rate tables based on detailed models of the brachytherapy sources are necessary for treatment planning. This work will present an away and along dose rate table for a 27 mm long catheter based 32P beta source. MD-55-2 radiochromic film has been exposed at five different depths (0.5 mm-4 mm) in a polystyrene phantom using a 27 mm long Guidant 32P beta source. The total dose to the active region of the film was determined using the absolute detector response of the MD-55-2 radiochromic film. The Monte Carlo code MCNP4B2 was also used to calculate the dose to the active region of the film using a detailed model of the source, encapsulation, and radiochromic film. The dose to film calculations showed good agreement with the measurements presented in this work with an average difference of 7%. The Monte Carlo calculations were also verified against previously published depth dose in water measurements determined using radiochromic film and plastic scintillator. The depth dose calculations in water showed good agreement with the previously published measurements with the calculations being about 2.5% lower than the film measurements and about 2.5% higher than the scintillator measurements. This work then uses the verified Monte Carlo code to present a dose rate table for the 32P intravascular beta source.

Topics: Brachytherapy; Coronary Restenosis; Electrons; Humans; Models, Statistical; Monte Carlo Method; Phantoms, Imaging; Phosphorus Radioisotopes; Reference Values; X-Ray Film

Monte Carlo simulations of dose distributions around radioactive stents are very time intensive. Thus, in order to calculate the dose distribution around a 188Re stent, we chose to test a point kernel method, a method which is known to be faster but the accuracy of which has not been established for this application. The dose point kernel method, which takes into account absorption in the strut material (=self-absorption), was based on different beta-emitting point source distributions in water by itself and surrounded by steel spheres of different thicknesses. This information was input into an integration routine that modeled either a Palmaz-Schatz or Multilink stent. The dose distributions around 198Au and 32P stents calculated with the dose point kernel method were compared to those calculated using EGS4 and MCNP 4B Monte Carlo methods. The resulting correction for self-absorption in steel was distance dependent and averaged 1.12 for 32P and 1.25 for 198Au stents. The dose point kernel method gave nearly identical results to these full Monte Carlo simulations and was thus used to calculate the dose distributions around a 188Re stent. Although 188Re has a half-life of only 17 hours, it is posited to be useful for radioactive restenosis prevention, given that a recently developed rapid electrodeposition procedure allows stents to be made radioactive, at predetermined activities, within 15 minutes. The dose point kernel calculations of a 188Re-coated Multilink stent were compared to its radiochromic film measurements. The dose fall-off agreed with the calculations within 5% over 0.4 to 3.5 mm from the stent surface. The dose point kernel method is a valuable tool to determine depth dose distributions around activated stents taking into account the detailed geometry and the self-absorption in the struts. It not only requires much less processing time than Monte Carlo methods, but also allows the use of higher resolutions in modeling the geometry, which leads to more accurate self-absorption correction factors.

Topics: Angioplasty, Balloon, Coronary; Biophysical Phenomena; Biophysics; Brachytherapy; Coronary Restenosis; Film Dosimetry; Gold Radioisotopes; Humans; Monte Carlo Method; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Rhenium; Stents

The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries.. Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA).. Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively).. 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.

Topics: Animals; Coronary Restenosis; Phosphorus Radioisotopes; Stents; Swine; Tunica Intima

To observe the effect of endovascular brachytherapy on the prevention of restenosis after interveneional therapy and to investigate its possible mechanisms.. In the balloon-injuried rabbit model, pathological sections of iliac arteries were observed and the changes of vascular histomorphology were estimated by computer analysis of photomicrograms. Using immunohistochemical techniques, proliferating cell nuclear antigen (PCNA) was quantified to assess the proliferation of vascular smooth muscle cells.. After rabbit iliac arteries were injured by balloon overstretch angioplasty, neointima were shown to be less proliferative in the irradiated group than in the control group, from PCNA scores. The formation of neointima was suppressed with the external elastic laminar area increasing and without the luminal area decreasing in the irradiation group.. Endovascular brachytherapy using a liquid 32P filled balloon catheter system could prevent restenosis possibly by inhibiting the formation of neointima and improving positive vascular remodeling.

Topics: Animals; Brachytherapy; Catheterization; Coronary Restenosis; Female; Iliac Artery; Male; Muscle, Smooth, Vascular; Phosphorus Radioisotopes; Proliferating Cell Nuclear Antigen; Rabbits