(Circulation. 1996;93:641-645.)
© 1996 American Heart Association, Inc.
Articles |
Pure ß-ParticleEmitting Stents Inhibit Neointima Formation in Rabbits
From the Department of Cardiology (C.H., M.S., W.K.) and the Department of Anatomy (R.K.), University of Heidelberg (Germany), and the Forschungszentrum Karlsruhe/Cyclotron Department (K.S., E.H., L.F., P.F.), Karlsruhe, Germany.
Correspondence to Christoph Hehrlein, MD, Department of Cardiology, University of Heidelberg, Bergheimerstr 58, 69115 Heidelberg, Germany.
Background Considerable experimental evidence exists that
neointimal hyperplasia after angioplasty is inhibited by
-irradiation of the treated arteries. A ß-particle
radiation is absorbed in tissue within a shorter distance away from the
source than -radiation and may be more suitable for localized
vessel irradiation. This study outlines a method to implant a
ß-particle–emitting radioisotope (32P;
half-life, 14.3 days) into metallic stents. The effects of these
stents on the inhibition of neointimal hyperplasia was
compared with conventional stents in a rabbit model.
Methods and Results 32P was produced by irradiation
of red amorphous phophorus (31P) with neutrons and was
implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept
apart from 31P in a mass separator. The radioisotope was
tightly fixed to the stents, and the ion implantation process did not
alter the surface texture. Stent activity levels of 4 and 13 µCi were
chosen for the study. Four and 12 weeks after placement of conventional
stents and 32P-implanted stents in rabbit iliac arteries,
vascular injury and neointima formation were studied by
histomorphometry. Immunostaining for smooth muscle cell
(SMC) 
-actin was performed to determine SMC cellularity in the
neointima. SMCs were quantified by computer-assisted
counting of -actin immunoreactive cells.
Endothelialization of the stents was evaluated by
immunostaining for endothelial cell von
Willebrand factor. No difference in vessel wall injury was
found after placement of conventional and 32P-implanted
stents. Neointima formation was potently inhibited by
32P-implanted stents only at an activity level of 13 µCi
after 4 and 12 weeks. Neointimal SMC cellularity was
reduced in 32P-implanted stents compared with conventional
stents. Radioactive stents were endothelialized after 4
weeks, but endothelialization was less dense than in
conventional stents.
Conclusions Neointima formation in rabbits is markedly suppressed by a ß-particle–emitting stent incorporating the radioisotope 32P. In this model, a dose-response relation with this type of radioactive stent was observed, indicating that a threshold radiation dose must be delivered to inhibit neointima formation after stent placement over the long term.
Key Words: stents • radioisotopes
This article has been cited by other articles:
 |
|
 |
|
  M Jaster, V Fuster, P Rosenthal, M Pauschinger, Q-V Tran, D Janssen, W Hinkelbein, P Schwimmbeck, H-P Schultheiss, and U Rauch Catheter based intracoronary brachytherapy leads to increased platelet activation Heart, February 1, 2004; 90(2): 160 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. A. Meyer, B. Nowak, K. Schuermann, A. Buecker, F. Moltzahn, A. Kulisch, N. Heussen, T. Gorgen, U. Bull, and R. W. Gunther Inhibition of Neointimal Proliferation with 188Re-labeled Self-Expanding Nitinol Stent in a Sheep Model Radiology, December 1, 2003; 229(3): 847 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.J. Wardeh, R. Albiero, I.P. Kay, A.H.M. Knook, W. Wijns, K. Kozuma, T. Nishida, V. Ferrero, P.C. Levendag, W.J. van der Giessen, et al. Angiographical Follow-Up After Radioactive "Cold Ends" Stent Implantation: A Multicenter Trial Circulation, February 5, 2002; 105(5): 550 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hehrlein, J. J. DeVries, A. Arab, S. D. Haller, K. Schloesser, F. O. Tio, and T. A. Fischell Failure of a Novel Balloon-Expandable {gamma}-Emitting (103Pd) Stent to Prevent Edge Effects Circulation, November 6, 2001; 104(19): 2358 - 2362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. van der Giessen, E. Regar, M. S. Harteveld, V. L.M.A. Coen, R. Bhagwandien, A. Au, P. C. Levendag, J. Ligthart, P. W. Serruys, A. den Boer, et al. "Edge Effect" of 32P Radioactive Stents Is Caused by the Combination of Chronic Stent Injury and Radioactive Dose Falloff Circulation, October 30, 2001; 104(18): 2236 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tepe, L. M. Dinkelborg, U. Brehme, P. Muschick, B. Noll, T. Dietrich, A. Greschniok, A. Baumbach, C. D. Claussen, and S. H. Duda Prophylaxis of Restenosis With 186Re-Labeled Stents in a Rabbit Model Circulation, August 6, 2001; 104(4): 480 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Arab, C. Bode, and C. Hehrlein The radioactive stent -- any chance of a resurrection? Eur. Heart J., August 1, 2001; 22(15): 1245 - 1247. [Abstract] [PDF]
|
|
|
|
|
|
A. Farb, S. Shroff, M. John, W. Sweet, and R. Virmani Late Arterial Responses (6 and 12 Months) After 32P {beta}-Emitting Stent Placement : Sustained Intimal Suppression With Incomplete Healing Circulation, April 10, 2001; 103(14): 1912 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.Y Salame, S Verheye, I.R Crocker, N.A.F Chronos, K.A Robinson, and S.B King III Intracoronary radiation therapy Eur. Heart J., April 2, 2001; 22(8): 629 - 647. [PDF]
|
|
|
|
|
|
A.J Wardeh, A.H.M Knook, I.P Kay, M Sabate, V.L.M.A Coen, D.P Foley, J.N Hamburger, P.C Levendag, W.J van der Giessen, and P.W Serruys Clinical and angiographical follow-up after implantation of a 6-12{micro}Ci radioactive stent in patients with coronary artery disease Eur. Heart J., April 2, 2001; 22(8): 669 - 675. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Al Suwaidi, P. B. Berger, and D. R. Holmes Jr Coronary Artery Stents JAMA, October 11, 2000; 284(14): 1828 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. P. Kay, M. Sabate, M. A. Costa, K. Kozuma, M. Albertal, W. J. van der Giessen, A. J. Wardeh, J. M. R. Ligthart, V. M. A. Coen, P. C. Levendag, et al. Positive Geometric Vascular Remodeling Is Seen After Catheter-Based Radiation Followed by Conventional Stent Implantation but Not After Radioactive Stent Implantation Circulation, September 19, 2000; 102(12): 1434 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S Ettenson and E. R Edelman Local drug delivery: an emerging approach in the treatment of restenosis Vascular Medicine, May 1, 2000; 5(2): 97 - 102. [Abstract] [PDF]
|
|
|
|
|
|
C. Schulz, C. Niederer, C. Andres, R. A. Herrmann, X. Lin, R. Henkelmann, W. Panzer, C. Herrmann, D. F. Regulla, I. Wolf, et al. Endovascular Irradiation From {beta}-Particle-Emitting Gold Stents Results in Increased Neointima Formation in a Porcine Restenosis Model Circulation, April 25, 2000; 101(16): 1970 - 1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Cloft, D. F. Kallmes, H.-B. Lin, S.-T. Li, W. F. Marx, S. B. Hudson, G. A. Helm, M. B. Lopes, J. K. McGraw, J. E. Dion, et al. Bovine Type I Collagen as an Endovascular Stent-Graft Material: Biocompatibility Study in Rabbits Radiology, February 1, 2000; 214(2): 557 - 562. [Abstract] [Full Text]
|
|
|
|
|
|
P. W. Serruys and I. P. Kay I Like the Candy, I Hate the Wrapper : The 32P Radioactive Stent Circulation, January 4, 2000; 101(1): 3 - 7. [Full Text] [PDF]
|
|
|
|
|
|
R. Albiero, M. Adamian, N. Kobayashi, A. Amato, M. Vaghetti, C. Di Mario, and A. Colombo Short- and Intermediate-Term Results of 32P Radioactive {beta}-Emitting Stent Implantation in Patients With Coronary Artery Disease : The Milan Dose-Response Study Circulation, January 4, 2000; 101(1): 18 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Vodovotz, R. Waksman, W.-H. Kim, B. Bhargava, R. C. Chan, and M. Leon Effects of Intracoronary Radiation on Thrombosis After Balloon Overstretch Injury in the Porcine Model Circulation, December 21, 1999; 100(25): 2527 - 2533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Taylor, P. D. Gorman, A. Farb, T. G. Hoopes, and R. Virmani Long-Term Coronary Vascular Response to 32P {beta}-Particle-Emitting Stents in a Canine Model Circulation, December 7, 1999; 100(23): 2366 - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P Lee, S. Lo, K. Forster, A. C Yeung, and S. N Oesterle Clinical applications of brachytherapy for the prevention of restenosis Vascular Medicine, November 1, 1999; 4(4): 257 - 268. [Abstract] [PDF]
|
|
|
|
|
|
A. J. Wardeh, I. P. Kay, M. Sabate, V. L. M. A. Coen, A. L. Gijzel, J. M. R. Ligthart, A. den Boer, P. C. Levendag, W. J. van der Giessen, and P. W. Serruys {beta}-Particle-Emitting Radioactive Stent Implantation : A Safety and Feasibility Study Circulation, October 19, 1999; 100(16): 1684 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Carter, D. Scott, L. Bailey, T. Hoopes, R. Jones, and R. Virmani Dose-Response Effects of 32P Radioactive Stents in an Atherosclerotic Porcine Coronary Model Circulation, October 5, 1999; 100(14): 1548 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sabate, P. W. Serruys, W. J. van der Giessen, J. M.R. Ligthart, V. L.M.A. Coen, I. P. Kay, A. L. Gijzel, A. J. Wardeh, A. den Boer, and P. C. Levendag Geometric Vascular Remodeling After Balloon Angioplasty and {beta}-Radiation Therapy : A Three-Dimensional Intravascular Ultrasound Study Circulation, September 14, 1999; 100(11): 1182 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hehrlein, S. Kaiser, R. Riessen, J.u. Metz, P. Fritz, and W. Kubler External beam radiation after stent implantation increases neointimal hyperplasia by augmenting smooth muscle cell proliferation and extracellular matrix accumulation J. Am. Coll. Cardiol., August 1, 1999; 34(2): 561 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Zurbrugg, M. Wied, G. D. Angelini, and R. Hetzer Reduction of intimal and medial thickening in sheathed vein grafts Ann. Thorac. Surg., July 1, 1999; 68(1): 79 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Topol and P. W. Serruys Frontiers in Interventional Cardiology Circulation, October 27, 1998; 98(17): 1802 - 1820. [Full Text] [PDF]
|
|
|
|
|
|
O. F. Bertrand, R. Sipehia, R. Mongrain, J. Rodes, J.-C. Tardif, L. Bilodeau, G. Cote, and M. G. Bourassa Biocompatibility aspects of new stent technology J. Am. Coll. Cardiol., September 1, 1998; 32(3): 562 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Brieger and E. Topol Local drug delivery systems and prevention of restenosis Cardiovasc Res, September 1, 1997; 35(3): 405 - 413. [Full Text] [PDF]
|
|
|
|
|
|
W. J. van der Giessen and P. W. Serruys ß-Particle–Emitting Stents Radiate Enthusiasm in the Search for Effective Prevention of Restenosis Circulation, November 15, 1996; 94(10): 2358 - 2360. [Full Text]
|
|
|
|
|
|
A. J. Carter, J. R. Laird, L. R. Bailey, T. G. Hoopes, A. Farb, D. R. Fischell, R. E. Fischell, T. A. Fischell, and R. Virmani Effects of Endovascular Radiation From a ß-Particle–Emitting Stent in a Porcine Coronary Restenosis Model: A Dose-Response Study Circulation, November 15, 1996; 94(10): 2364 - 2368. [Abstract] [Full Text]
|
|
|
|
|
|
T. A. Fischell Polymer Coatings for Stents: Can We Judge a Stent by Its Cover? Circulation, October 1, 1996; 94(7): 1494 - 1495. [Full Text]
|
|