Rhenium-188-Labeled DTPA: a new radiopharmaceutical for intravascular radiation therapy

Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h ( n =5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats ( n=5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.     

Evaluation of three rhenium-188 candidates for intravascular radiation therapy with liquid-filled balloons to prevent restenosis

BACKGROUND: Intravascular brachytherapy is an effective method for inhibiting coronary restenosis after percutaneous transluminal coronary angioplasty. A new concept for preventing restenosis is the use of a liquid-filled balloon containing a beta-ray-emitting radioisotope. Generator-produced rhenium-188 (Re-188) is a good candidate for intravascular brachytherapy. However, in the unlikely event of balloon rupture, release of Re-188 perrhenate may cause a high radiation dose to the thyroid and stomach. In this study, we compared the biodistributions of three Re-188 preparations (Re-188 perrhenate, Re-188 pentetic acid [DTPA], and Re-188 MAG3) to assess the radiation dose to organs in a rat model that mimicked balloon rupture. METHODS AND RESULTS: After injection of Re-188 preparations intravenously, rats were killed at 10 minutes, 30 minutes, 60 minutes, 2 hours, and 6 hours (n = 5/group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter. In addition, urine excretion and thyroid gland uptake were evaluated in rats (n = 5/group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed all 3 agents were excreted primarily via urine. In the Re-188 MAG3 group, 82% was excreted within 1 hour, but in the Re-188 perrhenate group, only 28% was excreted. The biodistribution data for these agents revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA and Re-188 MAG3 groups. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for all 3 agents. The thyroid radiation values were 0.163, 0.0167, and 0.00728 mGy/MBq for Re-188 perrhenate, Re-188 DTPA, and Re-188 MAG3, respectively. The stomach radiation values were 0.127 mGy/MBq for Re-188 perrhenate, 0.013 mGy/MBq for Re-188 DTPA, and 0.0104 mGy/MBq for Re-188 MAG3. CONCLUSIONS: In the event of balloon rupture, the release of Re-188 MAG3 or Re-188 DTPA results in lower radiation doses than release of Re-188 perrhenate, especially to the thyroid gland and the stomach.     

The availability of contrast media in the application of Holmium-166-DTPA for vascular brachytherapy

Since coronary angioplasty using a liquid radiation source is performed with computed tomography(CT) angiography, use of a CT contrast agent is a good alternative to see if the balloon has close contact with the blood vessel wall for the delivery of a sufficient radiation dose to the stenotic artery. In order to examine the usefulness of the CT contrast agent as a diluent of a liquid radiation source, various physicochemical studies and in vivo stability studies using animals were implemented using (166)Ho-DTPA for vascular brachytherapy and a PTCA balloon catheter. For this study, three CT contrast agents, Hexabrix (320)(Rx), Iomeron (350)(Rx) and Visipaque (320)(Rx) were used. Results showed that (166)Ho radiolabeled component of Hexabrix (320)(Rx) and the (166)Ho-complex was proposed to be (166)Ho-EDTA. However, in the case of Iomeron (350)(Rx) and Visipaque (320)(Rx), no other (166)Ho-complex was formed except the desired (166)Ho-DTPA. In the case where (166)Ho-EDTA (>98% radiolabeling yield) was administrated to rabbits, only 10% of the administered dose was excreted through the urinary track 30 min after injection. However, in the animal experiment where Hexabrix (320)(Rx) was added to the (166)Ho-DTPA vial with the volume ratio of 1:1, over 80% of the administrated dose accumulated into the bladder within 30 min after injection. Therefore, Hexabrix (320)(Rx) is applicable when it is used as a diluent of a (166)Ho-based liquid radiation source and its volume is applied in a minimal manner to visualize the balloon catheter. In conclusion, the use of a CT contrast agent in the clinical application of a liquid radiation source has beneficiary effects such as visualization of both the position and shape of the balloon are possible and most importantly, whether or not there is a formation of a void volume of liquid inside the balloon as well as the detection of radiation leakage on a real-time basis, on site during the angioplasty.     

Endovascular brachytherapy for the prevention of restenosis after angioplasty

Restenosis is an unsolved clinical and financial limitation of angioplasty. Local irradiation is a new approach for the reduction of restenosis. Several animal studies have demonstrated the effective inhibition of arterial neointimal proliferation by percutaneous or endovascular irradiation. High-dose-rate irradiation from gamma and beta sources can be applied from radioactive wires or seeds and from liquid beta-emitter-filled balloon catheters. Dosimetric calculations have been performed for all relevant radionuclides. An effective dose can be applied within 10 min to the treated arteries. Beta-emitters are characterized by a low tissue penetration, which simplifies radiation protection but complicates the achievement of a homogeneous dose distribution without centering of the irradiation source. Gamma-emitters are characterized by deep tissue penetration and delivery of almost the same dose to all vessel layers; however, considerable care with regard to radiation protection of the environment is required if gamma-emitters are used. The liquid-filled balloon ensures a homogeneous dose delivery due to the self-centring irradiation source but entails the possibility of radioactivity incorporation in the event of balloon rupture. The most attractive radionuclide for this purpose is rhenium-188, which is available from the 188W/188Re generator system. Radiation exposure after accidental incorporation can be limited by chelation with mercaptoacetyltriglycine or by subsequent oral administration of perchlorate. Initial clinical trials have demonstrated the feasibility of the various irradiation techniques and yielded encouraging results. The use of unsealed radioactivity in a balloon catheter involves the nuclear medicine physician in this new field of therapy. This review discusses the concepts, the radiotracers and the results of animal experiments and early clinical trials in the field of endovascular irradiation employed as a possible means to prevent restenosis after angioplasty.     

Endovascular brachytherapy for the prevention of restenosis after angioplasty

Restenosis is an unsolved clinical and financial limitation of angioplasty. Local irradiation is a new approach for the reduction of restenosis. Several animal studies have demonstrated the effective inhibition of arterial neointimal proliferation by percutaneous or endovascular irradiation. High-dose-rate irradiation from gamma and beta sources can be applied from radioactive wires or seeds and from liquid beta-emitter-filled balloon catheters. Dosimetric calculations have been performed for all relevant radionuclides. An effective dose can be applied within 10 min to the treated arteries. Beta-emitters are characterized by a low tissue penetration, which simplifies radiation protection but complicates the achievement of a homogeneous dose distribution without centring of the irradiation source. Gamma-emitters are characterized by deep tissue penetration and delivery of almost the same dose to all vessel layers; however, considerable care with regard to radiation protection of the environment is required if gamma-emitters are used. The liquid-filled balloon ensures a homogeneous dose delivery due to the self-centring irradiation source but entails the possibility of radioactivity incorporation in the event of balloon rupture. The most attractive radionuclide for this purpose is rhenium-188, which is available from the ¹⁸⁸W/¹⁸⁸Re generator system. Radiation exposure after accidental incorporation can be limited by chelation with mercaptoacetyltriglycine or by subsequent oral administration of perchlorate. Initial clinical trials have demonstrated the feasibility of the various irradiation techniques and yielded encouraging results. The use of unsealed radioactivity in a balloon catheter involves the nuclear medicine physician in this new field of therapy. This review discusses the concepts, the radiotracers and the results of animal experiments and early clinical trials in the field of endovascular irradiation employed as a possible means to prevent restenosis after angioplasty.     

Dosimetry of rhenium-188 diethylene triamine penta-acetic acid for endovascular intra-balloon brachytherapy after coronary angioplasty

To examine the possibility of using rhenium-188 diethylene triamine penta-acetic acid (DTPA) for endovascular intra-balloon brachytherapy after angioplasty, dose distribution around the balloon was calculated and validated by film dosimetry. Medical internal radiation dosimetry (MIRD) was calculated assuming that the balloon had ruptured and that the contents had been released into the systemic circulation. 188Re-perrhenate eluate from the 188W/188Re generator was concentrated using an ion column and used to label DTPA. The dose distribution around the angioplasty balloon (20 mm length, 3 mm diameter cylinder) was estimated by Monte Carlo simulation using the EGS4 code. The time required for 17.6 Gy to be absorbed at 1 mm from the balloon's surface following application of 3700 MBq/ml of 188Re was found to be 278 s. Fifty percent of the energy was deposited in the first millimetre of the vessel wall from the balloon's surface. The calculated radiation absorbed dose agreed with that measured by film dosimetry, which was performed using a water phantom, with errors ranging from 9.4% to 17%. Upon balloon rupture the total amount of 188Re-DTPA was presumed to enter the systemic circulation. The resulting radiation absorbed dose was calculated using the MIRDOSE3 program and residence times obtained from dogs and amounted to 0.0056 mGy/MBq to the whole body and 4.56 mGy/MBq to the urinary bladder. The absorbed dose of 188Re-DTPA to the whole body was one-tenth of that of 188Re-perrhenate. A window-based program was developed to calculate the exposure time and the radiation dose absorbed as a function of the 188Re concentration and the arbitrary distance from the balloon to the surrounding tissues. We conclude that 188Re-DTPA is easy to prepare, safe to use and suitable for intra-balloon brachytherapy after coronary angioplasty.     

血管内近距离放射治疗剂量影响因素的研究

目的　研究32 P球囊预防血管再狭窄的影响因素。方法　采用组织等效血管和热释光剂量学方法。结果　 2 5mm× 2 0mm空球囊内残留32 P对血管壁造成的剂量影响是 0 92Gy min。当球囊内导管偏离中心时 ,球囊外表面的吸收剂量将降低 2 0 %。气泡位置处的吸收剂量比球囊外表面平均吸收剂量低约 30 %。结论　32 P球囊表面轴向剂量分布较均匀 ,但径向吸收剂量随距离增加迅速减少。血管内近距离放射治疗有很好的临床应用前景。     

Post-stenting intravascular brachytherapy trials on hypercholesterolemic rabbits using 32P liquid sources: implications for prevention of in-stent restenosis

PURPOSE: Liquid sources of radiation delivered in angioplasty balloons may be a convenient self-centering device used for prevention of in-stent restenosis. To test the effectiveness of this method an intravascular brachytherapy study was performed using 32P liquid sources in an animal model. METHODS: The radial dose distribution around angioplasty balloons filled with solutions of Na 2H 32PO 4 was calibrated by thermoluminescence dosimetry. The animal experiments were performed in rabbits with induced hypercholesterolemia. The balloons containing 32P were introduced into iliac arteries immediately after stent implantation. Estimated 7-49 Gy doses required 30-100 min irradiations. Radiation effects were evaluated by comparing the thickness of various components of the artery wall. RESULTS: Doses of 7, 12, 16 or 49 Gy on the internal artery surface required 30-100 min of irradiation. The dose of 49 Gy at "zero" distance corresponding to 16 Gy at 1.0 mm from the balloon surface reduced hypertrophy in every layer of the arterial wall: in the intima the cross-sectional areas were 0.13 versus 0.91 mm 2, in the media were 0.5 versus 0.46 mm 2 and in the adventitia were 0.04 versus 0.3 mm 2 (p <0.05). A dose of 7 Gy at the balloon surface produced adverse irradiation effects: the intimal area of the artery was 2.087 versus 0.857 mm 2, the medial area was 0.59 versus 0.282 mm 2 and the adventitial area was 0.033 versus 0.209 mm 2 in treated and control arteries, respectively. CONCLUSION: Application of a 49 Gy irradiation dose to the internal arterial surface effectively prevented in-stent restenosis.     

Dosimetry of rhenium-188 diethylene triamine penta-acetic acid for endovascular intra-balloon brachytherapy after coronary angioplasty

To examine the possibility of using rhenium-188 diethylene triamine penta-acetic acid (DTPA) for endovascular intra-balloon brachytherapy after angioplasty, dose distribution around the balloon was calculated and validated by film dosimetry. Medical internal radiation dosimetry (MIRD) was calculated assuming that the balloon had ruptured and that the contents had been released into the systemic circulation. ¹⁸⁸Re-perrhenate eluate from the ¹⁸⁸W/¹⁸⁸Re generator was concentrated using an ion column and used to label DTPA. The dose distibution around the angioplasty balloon (20 mm length, 3 mm diameter cylinder) was estimated by Monte Carlo simulation using the EGS4 code. The time required for 17.6 Gy to be absorbed at 1 mm from the balloon’s surface following application of 3700 MBq/ml of ¹⁸⁸Re was found to be 278 s. Fifty percent of the energy was deposited in the first millimetre of the vessel wall from the balloon’s surface. The calculated radiation absorbed dose agreed with that measured by film dosimetry, which was performed using a water phantom, with errors ranging from 9.4% to 17%. Upon balloon rupture the total amount of ¹⁸⁸Re-DTPA was presumed to enter the systemic circulation. The resulting radiation absorbed dose was calculated using the MIRDOSE3 program and residence times obtained from dogs and amounted to 0.0056 mGy/MBq to the whole body and 4.56 mGy/MBq to the urinary bladder. The absorbed dose of ¹⁸⁸Re-DTPA to the whole body was one-tenth of that of ¹⁸⁸Re-perrhenate. A window-based program was developed to calculate the exposure time and the radiation dose absorbed as a function of the ¹⁸⁸Re concentration and the arbitrary distance from the balloon to the surrounding tissues. We conclude that ¹⁸⁸Re-DTPA is easy to prepare, safe to use and suitable for intra-balloon brachytherapy after coronary angioplasty. Received 27 May and in revised form 7 September 1999     

Increased expression of nuclear NF-kappaB after coronary artery balloon injury can be inhibited by intracoronary beta-irradiation

PURPOSE: Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-kappaB) in neointimal hyperplasia following intracoronary irradiation. MATERIALS AND METHODS: Fifty-four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, beta-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 ((188)Re) beta-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination. RESULTS: Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy (188)Re beta-irradiation, respectively. The expression of arterial NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-kappaB p65 expression in both gene and protein levels, and such induction could be significantly reduced by (188)Re beta-irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the beta-irradiation could not be observed in ICAM-1 and VCAM-1. CONCLUSION: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-kappaB p65.     

Increased expression of nuclear NF-kappaB after coronary artery balloon injury can be inhibited by intracoronary beta-irradiation

Purpose: Molecular mechanisms by which balloon angioplasty injury-induced neointimal hyperplasia can be reduced by intravascular brachytherapy are unclear. We investigated the role of nuclear factor-kappaB (NF-κB) in neointimal hyperplasia following intracoronary irradiation.

Materials and methods: Fifty-four coronary arteries from 30 pigs were divided into 6 groups: sham control, balloon angioplasty injury alone, β-irradiation at doses of 14 or 20 Gy, and 14 or 20 Gy beta-irradiation immediately followed by balloon injury. Coronary arteries were injured by overstretch balloon angioplasty and then the arteries were irradiated using a Rhenium-188 (¹⁸⁸Re) β-emitting solution-filled balloon. Pigs were scarified one day or one week after coronary interventions for molecular detection and six weeks after the procedures for histological examination.

Results: Six weeks after coronary interventions, the histological results show that balloon angioplasty injury had induced intimal hyperplasia in coronary artery but the response was significantly reduced by 28% and 60% when the injury was immediately treated by 14 and 20 Gy ¹⁸⁸Re β-irradiation, respectively. The expression of arterial NF-κB p65, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were detected at one day and one week after the procedures. The treatment of balloon injury could significantly induce the NF-κB p65 expression in both gene and protein levels, and such induction could be significantly reduced by ¹⁸⁸Re β-irradiation at dose of 20 Gy. However, the similar result on the regulation of gene expression affected by the β-irradiation could not be observed in ICAM-1 and VCAM-1.

Conclusion: The inhibitory effect of intracoronary brachytherapy on neointimal formation following overstretch balloon angioplasty could involve inhibition of NF-κB p65.     

Intravascular radiation therapy after balloon angioplasty of narrowed femoropopliteal arteries to prevent restenosis: results of the PARIS feasibility clinical trial

PURPOSE: To conduct a feasibility study to assess the feasibility, safety, and outcome of endoluminal gamma radiation therapy after balloon angioplasty of superficial femoral artery (SFA) lesions. MATERIALS AND METHODS: Forty patients with claudication were enrolled in the study and underwent percutaneous transluminal angioplasty (PTA) of SFA lesions with a mean lesion length of 9.8 cm +/- 3.0 and a mean reference vessel diameter of 5.2 mm +/- 3.1. After successful PTA, a segmented centering balloon catheter was positioned to cover the PTA site. The patients were then transported to the radiation oncology suite and treated with a microSelectron HDR afterloader with use of an Ir-192 source with a prescribed dose of 14 Gy, 2 mm into the vessel wall. Ankle-brachial index (ABI) and Rutherford score were evaluated at 1, 6, and 12 months after the procedure and angiographic follow-up was conducted at 6 months. RESULTS: Radiation was delivered successfully to 35 of 40 patients. There were no procedural complications. Exercise and rest ABI were higher at 1 year (0.72 +/- 0.26 and 0.89 +/- 0.18, respectively) compared to baseline (0.51 +/- 0.25 and 0.67 +/- 0.17, respectively). Maximum walking time on a treadmill increased from 3.41 min +/- 2.41 to 4.43 min +/- 2.49 at 30 days and was 4.04 min +/- 2.8 at 12 months. The angiographic binary restenosis rate at 6 months was 17.2% and the clinical restenosis rate at 12 months was 13.3%. There were no angiographic or clinical adverse events related to the radiation therapy. CONCLUSIONS: Intraarterial radiation after PTA of SFA lesions with use of high-dose rate gamma radiation is feasible and safe. The angiographic and clinical improvements are sustainable at 1 year and represent a potent antirestenotic therapy for the treatment of narrowed peripheral arteries.     

Cryoplasty for the Prevention of Arterial Restenosis

Restenosis after percutaneous transluminal angioplasty remains the limiting factor for the long-term benefit of endovascular therapies of peripheral arterial occlusive disease. Despite a variety of modifications and adjuncts to angioplasty such as bare metal stents, covered stents, and drug-eluting stents as well as a number of new technologies like laser angioplasty and cutting balloon angioplasty, restenosis rates have not been significantly affected and remain inferior to those for surgery for long lesions in the femoropopliteal segment. Cryoplasty, which combines balloon angioplasty with the application of cryothermal energy to the vessel wall, was suggested as a promising approach to prevent the formation of neointimal hyperplasia after angioplasty procedures. This review discusses the basic principles of cryoplasty, summarizes the current data on restenosis rates after cryoplasty treatment, and evaluates cryoplasty as a new treatment method to solve the problems associated with restenosis development. The results of the clinical studies suggest that cryoplasty is a feasible and safe technique in the treatment of femoropopliteal disease, however, they have failed to prove any superiority of cryoplasty over conventional angioplasty.     

Dye laser-assisted angioplasty with multifiber catheters: short-term results in the treatment of 29 peripheral arterial occlusions

The use of pulsed dye laser energy for angioplasty offers the possibility of ablating atherosclerotic plaques without thermal damage to the adjacent arterial wall. However, to be of value, systems that deliver the energy safely and effectively are required. We tested multifiber catheters in 504-nm pulsed dye laser angioplasty for treatment of peripheral arterial occlusions. Flexible multifiber catheters consist of 12 (7-French) and 19 (9-French) concentrically arranged 200-microns quartz fibers allowing guidewire-directed use. Laser-assisted angioplasty was performed in 2- to 13-cm- (mean, 7.5-cm) long occlusions of iliac (six) and femoropopliteal (23) arteries in patients with symptomatic occlusive vascular disease. Angiograms were obtained before and after laser ablation, after subsequent balloon dilatation, and if signs or symptoms indicated restenosis, during follow-up. The laser procedure was impossible to perform in three (10%) of 29 patients; this was related to unsuccessful passage of the wire in one patient and to inability to advance the laser catheter across the lesion in two patients. In one other patient, reocclusion occurred 1 day after angioplasty. Stand-alone laser angioplasty relieved residual stenosis of less than 30% in six (26%) of 23 femoropopliteal arteries, making balloon dilatation dispensable. Immediate clinical improvement was achieved in 26 (90%) of 29 patients. Laser treatment caused no perforation and no embolization, but minor dissections occurred in 36% of the patients. Our experience suggests that pulsed dye laser angioplasty via multifiber catheters converts arterial occlusions into stenoses. With the exception of angioplasty in distal femoropopliteal arteries, additional balloon dilatation is necessary to complete recanalization.     

Intracoronary β-brachytherapy using a rhenium-188 filled balloon catheter in restenotic lesions of native coronary arteries and venous bypass grafts

Purpose We have previously demonstrated the efficacy of intracoronary β-brachytherapy using a liquid ¹⁸⁸Re-filled balloon in a randomised trial including de novo lesions. Percutaneous coronary interventions in restenotic lesions and in stenoses of venous bypass grafts are characterised by a high recurrence rate for restenosis and re-interventions. Against this background, we wanted to assess the impact of intracoronary β-brachytherapy using a liquid ¹⁸⁸Re-filled balloon in restenotic lesions in native coronary arteries and venous bypass grafts.Methods In 243 patients, β-brachytherapy with 22.5 Gy was applied at a tissue depth of 0.5 mm. Patients were followed up angiographically after 6 months and clinically for 12 months. The primary clinical endpoint was the incidence of MACE (death, myocardial infarction, target vessel revascularisation). Secondary angiographic endpoints were late loss and binary restenosis rate in the total segment.Results All irradiation procedures were successfully performed. A total of 222 lesions were in native coronary arteries; 21 were bypass lesions. Mean irradiation length was 41.6±17.3 mm (range 20–150 mm) in native coronary arteries and 48.1±33.9 mm (range 30–180 mm) in bypass lesions; the reference diameter was 2.57±0.52 mm and 2.83±0.76 mm, respectively. There was no vessel thrombosis during antiplatelet therapy. Angiographic/clinical follow-up rate was 84%/100%. MACE rate was 17.6% in the native coronary artery group and 38.1% in the CABG group (p<0.03). Binary restenosis rate was 22.5% and 55.6% (p<0.01), and late loss was 0.38±0.72 mm and 1.33±1.11 mm (p<0.001), respectively.Conclusions We conclude that intracoronary β-brachytherapy with a liquid ¹⁸⁸Re-filled balloon using 22.5 Gy at a tissue depth of 0.5 mm in restenotic lesions is safe. It is associated with a low binary restenosis rate, resulting in a low occurrence rate of MACE within 12 months in restenotic lesions in native coronary arteries but not in vein grafts.     

Potential 166Ho radiopharmaceuticals for endovascular radionuclide therapy. II. Preparation and evaluation of 166Ho-DTPA

166Ho, with its favourable radiation characteristics of t(1/2) 26.8 h and Ebeta 1.85 and 1.75 MeV, is proposed as a suitable choice for the endovascular radionuclide therapy (EVRT) technique of liquid filled, low pressure balloon angioplasty. 166Ho was produced by the (n,gamma) reaction on a natural Ho2O3 target. The specific activity obtained was approximately 100 mCi x mg(-1) when irradiated at a flux of 2 x 10(13) n x cm(-2) s(-1) for approximately 7 days, and the possible contaminant 166Ho(m) was not detected. 166Ho was easily complexed with diethylenetriaminepentaacetic acid (DTPA) at a ligand to metal molar ratio ([L]:[M]) of 1:1 at room temperature (22-23 degrees C) and a reaction time of a few minutes. The radiochemical purity was >99%, as determined by paper chromatography using a mixture of pyridine, ethanol and water (1:2:4) as solvent. The complex had good stability up to 72 h at 37 degrees C in a serum environment. In a study using Swiss mice > 85% of the injected dose was cleared into the urine within 30 min post-injection, with insignificant retention in any major tissues. The studies show that the 166Ho-DTPA complex could be an alternative to the more expensive and difficult to access 188Re based products for EVRT, and provide adequate uniform radiation dose for the arterial vessel wall under treatment.     

Peripheral Stent Placement in Hemodialysis Grafts

The purpose of the present study was to evaluate the clinical outcome of peripheral stent placement after failed balloon angioplasty in patients with grafts who are on hemodialysis. We examined 30 Wallstents that were placed in 26 patients because balloon angioplasty failed or early restenosis (<3 months) occurred within 3 months. We retrospectively reviewed 267 consecutive balloon angioplasties performed in 71 patients with graft access between August 2000 and March 2007. Stent placements accounted for 30 (11.2%) of the 267 balloon angioplasties. The clinical success rate of stent placement was 93.3% (28 of 30 stent placements). The 3-, 6-, and 12-month primary patency rates were 73.3%, 39.3%, and 17.7%, respectively. The 1-, 2-, and 3-year secondary patency rates were 90.2%, 83.8%, and 83.8%, respectively. Primary patency was significantly prolonged by stent placement after early restenosis compared with previous balloon angioplasty alone (P = 0.0059). Primary patency after stent placement was significantly lower than after successful balloon angioplasty without indications for stent placement (P = 0.0279). Secondary patency rates did not significantly differ between stent placement and balloon angioplasty alone. The mean number of reinterventions required to maintain secondary patency after stent placement was significantly larger than that after balloon angioplasty alone (Mann–Whitney U test, P = 0.0419). We concluded that peripheral stent placement for graft access is effective for salvaging vascular access after failed balloon angioplasty and for prolonging patency in early restenosis after balloon angioplasty. However, reinterventions are required to maintain secondary patency after stent placement. Furthermore, peripheral stent placement for graft access cannot achieve the same primary patency as balloon angioplasty alone.     

Efficacy of Local Molsidomine Delivery from a Hydrogel-Coated Angioplasty Balloon Catheter in the Atherosclerotic Porcine Model

Purpose: To evaluate the therapeutic effects of local molsidomine delivery via a hydrogel-coated angioplasty balloon catheter during overstretch angioplasty in atherosclerotic swine iliac vessels. Molsidomine is retained in the arterial wall after local delivery for more than 72 hr and is slowly metabolized into linsidomine, releasing nitric oxide (NO). Methods: A hydrogel-coated angioplasty balloon catheter was used to both deliver drug locally (150 mg molsidomine or placebo in the contralateral vessel) and dilate iliac vessels in nine Pietrin pigs that had been on an atherogenic diet for 5 months. Animals were killed at 3 hr (n = 2), 24 hr (n = 3) and 3 months (n = 3) after treatment. Iliac arteries were examined for wall pulsatility, histomorphometry, cell proliferation and platelet aggregation. Results: No significant therapeutic effects were detected 3 hr after treatment. At 24 hr, wall pulsatility, thromboresistance and vascular cell homeostasis were significantly restored in the molsidomine-treated versus placebo group. At 3 months, molsidomine inhibited restenotic lesion development, except in scarred areas of histologically detectable adventitial/medial dissection. Conclusion: Local delivery of concentrated molsidomine from a hydrogel-coated angioplasty balloon catheter resulted in early NO-dependent vasodilation/stress normalization and antithrombotic and antiproliferative effects. In the medium term, molsidomine inhibited restenosis in the absence of vessel dissection.     

188Re-ethylene dicysteine: a novel agent for possible use in endovascular radiation therapy

Several agents, such as 188ReO4-, 188Re-MAG3 and 188Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since 99Tcm labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of 186Re-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously. Therefore, it was of interest to evaluate the applicability of the more potential isotope of rhenium, 188Re, a high energy beta-emitter (Ebetamax = 2.12 MeV) with a suitable T 1/2 = 16.9 h, obtainable carrier-free from the 188W-188Re generator, as an attractive and alternative radionuclide for labelling with L,L-EC. In this paper, the preparation and pharmacological behaviour of the 188Re complex of ethylene dicysteine are reported. The complex can be prepared in high yields (99.5%) under optimized conditions of pH 2-3, at a ligand concentration of 15 mM, 50 microg (0.18 mM) carrier rhenium and using 2 mg x mL(-1) stannous chloride. On storage at 4 degrees C, the RC purity was more than 97% after 48 h when prepared under optimum conditions. Biodistribution studies in Wistar rats showed the desired characteristics of fast blood clearance and low retention of activity in the vital organs (< 2% in intestine, < 1% in stomach, < 0.5% in liver) with a high renal excretion (90.65+/-0.6%) at 3 h post-injection. These results confirm the advantages of using the 188Re-EC complex compared with perrhenate and other rhenium radiopharmaceuticals currently being used in balloons for EVRT.     

Adjuvant use of abciximab for balloon angioplasty of symptomatic middle cerebral artery stenosis

PURPOSE: To evaluate the safety of adjuvant intravenous use of abciximab in balloon angioplasty for symptomatic middle cerebral artery stenosis. MATERIAL AND METHODS: Seven patients with symptomatic stenosis at the main trunk (n=5), or proximal post-trifurcation portion (n=2) of the middle cerebral artery, were enrolled in the study. A bolus dose of abciximab (0.15 mg/kg) was given intravenously immediately before the procedure. The immediate morphologic results as well as the presence of hyperacute thrombosis or hemorrhage after angioplasty were evaluated. Clinical evaluation was performed 1 day and 1 month following angioplasty. Oral antiplatelets were administered during the follow-up period. Follow-up angiography was performed after 7 to 14 (mean 10.4) months. Stenosis of a vessel greater than 50% was considered as restenosis. RESULTS: The procedure was technically successful in all patients. Immediate residual stenosis was insignificant in 4 and mild (less than 50%) in 3 patients. There was no evidence of intimal dissection. Mild gum bleeding was noted in two patients. All study patients were clinically stable at follow-up without newly developed neurological abnormality even though there was one case of occlusion and one case of restenosis on follow-up angiography. Angiographic patency rate was 71%. CONCLUSION: In performing proximal middle cerebral artery balloon angioplasty, abciximab may be safely used to prevent acute thrombosis. The mid-term patency of the vessels was also acceptable.