Overview of Intracoronary Brachytherapy for in-Stent Restenosis of a Drug-Eluting Stent

Document Type : Review Article


1 Medical Physics Specialist, Department of Medical Physics, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

2 Medical Radiation Science Specialist, Department of Medical Radiation Science, School of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


Percutaneous coronary intervention with stenting is considered recently as the most common procedure for the treatment of symptomatic coronary. The article reviewed 41 studies published during 1997-2019 on intracoronary brachytherapy for in-stent restenosis of a drug-eluting stent. Intracoronary radiation therapy was finally confirmed in the setting of in-stent restenosis using as adjunctive therapy. Irradiation dose to vessels may result in fibrosis, which can, in turn, cause the late formation of an aneurysm due to the weakness of the vessel wall. Intracoronary brachytherapy is a critical treatment which should not be ignored. 


1.      Alraies MC, Darmoch F, Tummala R, Waksman R. Diagnosis and management challenges of in-stent restenosis in coronary arteries. World J Cardiol. 2017; 9:640.
2.         Waksman R, Steinvil A. In-stent restenosis? The raiders of the magic remedy. Am Heart Assoc. 2016; 9:e004150.
3.         Piccolo R, Stefanini GG, Franzone A, Spitzer E, Blöchlinger S, Heg D, et al. Safety and efficacy of resolute zotarolimus-eluting stents compared with everolimus-eluting stents: a meta-analysis. Circulation. 2015; 8:e002223.
4.         Derkacz A, Szymczyszyn A, Szahidewicz-Krupska E, Protasiewicz M. Effect of endovascular coronary low-level laser therapy during angioplasty on the release of endothelin-1 and nitric oxide. Age. 2017; 14:687.
5.         Minar E, Pokrajac B, Maca T, Ahmadi R, Fellner C, Mittlböck M, et al. Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty: results of a prospective randomized study. Circulation. 2000; 102:2694-9.
6.         Wolfram RM, Pokrajac B, Ahmadi R, Fellner C, Gyongyosi M, Haumer M, et al. Endovascular brachytherapy for prophylaxis against restenosis after long-segment femoropopliteal placement of stents: initial results. Radiology. 2001; 220:724-9.
7.         Neamtu I, Chiriac AP, Diaconu A, Nita LE, Balan V, Nistor MT. Current concepts on cardiovascular stent devices. Mini Rev Med Chem. 2014; 14:505-36.
8.         Ohri N, Sharma S, Kini A, Baber U, Aquino M, Roy S, et al. Intracoronary brachytherapy for in-stent restenosis of drug-eluting stents. Adv Radiat Oncol. 2016; 1:4-9.
9.         Negi SI, Torguson R, Gai J, Kiramijyan S, Koifman E, Chan R, et al. Intracoronary brachytherapy for recurrent drug-eluting stent failure. JACC. 2016; 9:1259-65.
10.       Iofina E, Radke P, Schubert D, Langenberg R, Blindt R, Hanrath P, et al. Three‐year follow‐up after intracoronary beta‐radiation therapy for in‐stent restenosis. Catheter Cardiovasc Interv. 2006; 67:600-6.
11.       Kleiman NS . Too Thick to Cut With SISRs: Brachytherapy in Multilayer Drug-Eluting Stent Restenosis.(2019).
12.       Garg S, Smith K, Torguson R, Okabe T, Slottow TL, Steinberg DH, et al. Treatment of drug‐eluting stent restenosis with the same versus different drug‐eluting stent. Catheter Cardiovasc Interv. 2007; 70:9-14.
13.       Roa DE, Song H, Yue N, d'Errico F, Nath R. Measured TG-60 dosimetric parameters of the Novoste Beta-Cath 90Sr/Y source trains for intravascular brachytherapy. Cardiovasc Radiat Med. 2002; 3:199-204.
14. Moosavi-Movahedi AA, Golchin AR, Nazari KK, Chamani J, Saboury AA, Bathaie SZ, Tangestani-Nejad S. Microcalorimetry, energetics and binding studies of DNA–dimethyltin dichloride complexes. Thermochim Acta. 2004; 414: 233-241.
15.       Williams DO, Sobieszczyk P. Coronary brachytherapy 2016. JACC Cardiovasc Interv. 2016; 9:1266-8.
16.       Knapp FF, Spencer RH, Kropp J. Intravascular radiation therapy with radioactive liquid-filled balloons for inhibition of restenosis after angioplasty: a new opportunity for nuclear medicine? J Nucl Med. 2001; 42:1384-7.
17.       Weinberger J, Giedd KN, Simon AD, Marboe C, Knapp FF, Trichter F, et al. Radioactive beta-emitting solution-filled balloon treatment prevents porcine coronary restenosis. Cardiovasc Radiat Med. 1999; 1:252-6.
18. Chamani J, Heshmati M. Mechanism for stabilization of the molten globule state of papain by sodium n-alkyl sulfates: spectroscopic and calorimetric approaches. J Colloid Interface Sci. 2008; 322: 119-127.
19.       Kiavar O, Sadeghi M. Modeling and dose calculations of a pure beta emitting sup 32P coated stent for intracoronary brachytherapy by Monte Carlo code. Int J Radiat Res. 2012; 9:257-63.
20.       Monroy-Guzman F, Almaraz VB, Gutierrez TR, Cohen LG, Nava PR, Rosales CJ, et al. Development of inorganic adsorbents as matrices of generators for therapeutic radionuclides. Therapeutic radionuclide generators: 90 Sr/90 Y and 188 W/188 Re generators. Vienna: Nternational Atomic Energy Agency; 2009.
21.       Jaeckel B, Cripps R, Güntay S, Bruchertseifer H. Development of semi-automated system for preparation of 188Re aqueous solutions of high and reproducible activity concentrations. Appl Radiat Isotopes. 2005; 63:299-304.
22.       Sarkar SK, Venkatesh M, Ramamoorthy N. Evaluation of two methods for concentrating perrhenate (188Re) eluates obtained from 188W–188Re generator. Appl Radiat Isotopes. 2009; 67:234-9.
23.       Mohammadi M, Islamian JP, Karami H, Oladghaffari M, Farajollahi A, Nejati-Koshki K. Role of HDM2 gene in radio-sensitivity of esophageal cancer cell lines to irradiation. Int J Cancer Manag. 2017; 10:6.
24.       Islamian JP, Mohammadi M, Baradaran B, Farajollahi A, Aghamiri SM, Jafarabadi MA, et al. Enhancing radiosensitivity of TE1, TE8, and TE 11 esophageal squamous carcinoma cell lines by Hdm2-siRNA targeted gene therapy in vitro. Bioimpacts. 2016; 6:93-8.
25.       Islamian JP, Mohammadi M, Baradaran B. Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview. Cancer Biol Med. 2014; 11:78.
26.       Rahgoshai S, Mohammadi M, Refahi S, Oladghaffari M, Aghamiri SM. Protective effects of IMOD and cimetidine against radiation-induced cellular damage. J Biomed Phys Eng. 2018; 8:133.
27.       Leon MB, Teirstein PS, Moses JW, Tripuraneni P, Lansky AJ, Jani S, et al. Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting. N Engl J Med. 2001; 344:250-6.
28.       Farb A, Burke AP, Kolodgie FD, Virmani R. Pathological mechanisms of fatal late coronary stent thrombosis in humans. Circulation. 2003; 108:1701-6.
29.       Hedman M, Hartikainen J, Syvänne M, Stjernvall J, Hedman A, Kivelä A, et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation. 2003; 107:2677-83.
30.       Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007; 115:2344-51.
31. Zolfagharzadeh M, Pirouzi M, Asoodeh A, Saberi MR, Chamani J. A comparison investigation of DNP-binding effects to HSA and HTF by spectroscopic and molecular modeling techniques. J Biomol Struct Dyn. 2014; 32:1936-1952.
32.       Hansrani M, Overbeck K, Smout J, Stansby G. Intravascular brachytherapy: a systematic review of its role in reducing restenosis after endovascular treatment in peripheral arterial disease. Eur J Vascular Endovasc Surg. 2002; 24:377-82.
33.       Kotzerke J, Hanke H, Höher M. Endovascular brachytherapy for the prevention of restenosis after angioplasty. Eur J Nucl Med. 2000; 27:223-36.
34.       Sabaté M, Costa MA, Kozuma K, Kay IP, Van Der Wiel CJ, Verin V, et al. Methodological and clinical implications of the relocation of the minimal luminal diameter after intracoronary radiation therapy. J Am Coll Cardiol. 2000; 36:1536-41.
35.       Mohammadi M, Danaee L, Alizadeh E. Reduction of radiation risk to interventional cardiologists and patients during angiography and coronary angioplasty. J Tehran Univ Heart Center. 2017; 12:101.
36. Sanei H, Asoodeh A, Hamedakbari-Tusi S, Chamani J. Multi-spectroscopic investigations of aspirin and colchicine interactions with human hemoglobin: binary and ternary systems. J Solution Chem. 2011; 40:1905-1931.
37.       Pavlides GS. Brachytherapy for treatment of restenosis after percutaneous coronary intervention. Hellenic J Cardiol. 2002; 43:216-8.
38.       Schroeder S, Kopp AF, Baumbach A, Meisner C, Kuettner A, Georg C, et al. Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. J Am Coll Cardiol. 2001; 37:1430-5.
39.       Teirstein PS, Massullo V, Jani S, Popma JJ, Mintz GS, Russo RJ, et al. Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med. 1997; 336:1697-703.
40.       Sheppard R, Eisenberg MJ. Intracoronary radiotherapy for restenosis. Mass Medical Soc. 2001; 344:295-7.
41.       Torguson R, Sabate M, Deible R, Smith K, Chu WW, Kent KM, et al. Intravascular brachytherapy versus drug-eluting stents for the treatment of patients with drug-eluting stent restenosis. Am J Cardiol. 2006; 98:1340-4.
42.       Waksman R, Bhargava B, Leon MB. Late thrombosis following intracoronary brachytherapy. Catheterizat Cardiovasc Interv. 2000; 49:344-7.
43.       Tangwongsan C, Chachati L, Webster JG, Farrell PV. In vitro calibration of a system for measurement of in vivo convective heat transfer coefficient in animals. Biomed Eng Online. 2006; 5:57.
44. Naeeminejad S, Assaran Darban R, Beigoli S, Saberi MR, Chamani J. Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques. J Biomol Struct Dyn. 2017; 35: 3250-3267.
45.       Regar E, Kozuma K, Sianos G, Coen VL, van der Giessen WJ, Foley D, et al. Routine intracoronary beta-irradiation. Acute and one year outcome in patients at high risk for recurrence of stenosis. Eur Heart J. 2002; 23:1038-44.
46.       De Benedetti E, Latchem D, Roguelov C, Coucke P, Seydoux C, Goy JJ, et al. Repeated intracoronary beta radiation for recurrent in‐stent restenosis. Catheterizat Cardiovasc Interv. 2002; 55:233-6.
47.       DeCunha JM, Enger SA. A new delivery system to resolve dosimetric issues in intravascular brachytherapy. Brachytherapy. 2018 May 1;17(3):634-43.