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In Vitro Comparison of the Antiproliferative Effects of Rhenium-186 and Rhenium-188 on Human Aortic Endothelial Cells

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Abstract

Purpose

Rhenium-186 (186Re) and rhenium-188 (188Re) are promising radionuclides for the inhibition of restenosis after percutaneous transluminal angioplasty or other vascular interventions. Until now the maximal dose tolerance of endothelial cells has not been clearly known.

Materials and Methods

To characterize the effects of local irradiation treatment, human aortic endothelial cells (ECs) were incubated with different doses of 186Re and 188Re. Two days after plating, ECs received treatment for a period of 5 days. The total radiation doses applied were 1, 4, 8, 16, and 32 Gy. On days 1, 3, 5, 7, and 12 after initial rhenium incubation, cell growth, clonogenic activity, cell-cycle distribution, and cytoskeletal architecture were evaluated.

Results

From the first day on, a dose-dependent growth inhibition was observed. Cumulative doses of ≥32 Gy caused a weak colony formation and significant alterations in the cytoskeletal architecture. An increased fraction of cells in G2/M phase was seen for cumulative radiation doses of ≥16 Gy. Interestingly, there were no significant differences between 186Re and 188Re.

Conclusion

Even for low dose rates of β particles a dose-dependent proliferation inhibition of ECs is seen. Doses beyond 32 Gy alter the cytoskeletal architecture with possibly endothelial dysfunction and late thrombosis.

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References

  1. Patel SD, Waltham M, Wadoodi A et al (2010) The role of endothelial cells and their progenitors in intimal hyperplasia. Ther Adv Cardiovasc Dis 4:129–141

    Article  PubMed  CAS  Google Scholar 

  2. Shoji M, Sata M, Fukuda D et al (2004) Temporal and spatial characterization of cellular constituents during neointimal hyperplasia after vascular injury: potential contribution of bone-marrow-derived progenitors to arterial remodeling. Cardiovasc Pathol 13:306–312

    Article  PubMed  Google Scholar 

  3. Smith SH, Geer JC (1983) Morphology of saphenous vein–coronary artery bypass grafts: seven to 116 months after surgery. Arch Pathol Lab Med 107:13–18

    PubMed  CAS  Google Scholar 

  4. Landmesser U, Hornig B, Drexler H (2004) Endothelial function: a critical determinant in atherosclerosis? Circulation 109:27–33

    Article  Google Scholar 

  5. Patti G, Pasceri V, Melfi R et al (2005) Impaired flow-mediated dilation and risk of restenosis in patients undergoing coronary stent implantation. Circulation 111:70–75

    Article  PubMed  Google Scholar 

  6. McEver RP, Cummings RD (1997) Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest 100:S97–S103

    Article  PubMed  CAS  Google Scholar 

  7. Welt FG, Rogers C (2002) Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc Biol 22:1769–1776

    Article  PubMed  CAS  Google Scholar 

  8. Werner N, Junk S, Laufs U et al (2003) Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res 93:e17–e24

    Article  PubMed  CAS  Google Scholar 

  9. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168–175

    Article  PubMed  CAS  Google Scholar 

  10. Snow AD, Bolender RP, Wight TN, Clowes AW (1990) Heparin modulates the composition of the extracellular matrix domain surrounding arterial smooth muscle cells. Am J Pathol 137:313–330

    PubMed  CAS  Google Scholar 

  11. Costa MA, Simon DI (2005) Molecular basis of restenosis and drug-eluting stents. Circulation 111:2257–2273

    Article  PubMed  Google Scholar 

  12. Liermann D, Bottcher HD, Kollath J et al (1994) Prophylactic endovascular radiotherapy to prevent intimal hyperplasia after stent implantation in femoropopliteal arteries. Cardiovasc Intervent Radiol 17:12–16

    Article  PubMed  CAS  Google Scholar 

  13. Wohlgemuth WA, Leissner G, Wengenmair H et al (2008) Endovascular brachytherapy in the femoropopliteal segment using 192Ir and 188Re. Cardiovasc Intervent Radiol 31:698–708

    Article  PubMed  Google Scholar 

  14. Wyttenbach R, Gallino A, Alerci M et al (2004) Effects of percutaneous transluminal angioplasty and endovascular brachytherapy on vascular remodeling of human femoropopliteal artery by noninvasive magnetic resonance imaging. Circulation 110:1156–1161

    Article  PubMed  Google Scholar 

  15. Christen T, Verin V, Bochaton-Piallat M et al (2001) Mechanisms of neointima formation and remodeling in the porcine coronary artery. Circulation 103:882–888

    PubMed  CAS  Google Scholar 

  16. Koshy SK, Kleiman NS, George LK et al (2008) Vascular changes and black hole phenomenon after coronary brachytherapy: a pathologically distinct entity. J Invasive Cardiol 20:560–562

    PubMed  Google Scholar 

  17. Wohlgemuth WA, Bohndorf K (2003) Endovascular brachytherapy to prevent restenosis after angioplasty. Rofo 175:246–252

    PubMed  CAS  Google Scholar 

  18. Sureka CS, Sunny CS, Subbaiah KV et al (2007) Dose distribution for endovascular brachytherapy using Ir-192 sources: comparison of Monte Carlo calculations with radiochromic film measurements. Phys Med Biol 52:525–537

    Article  PubMed  CAS  Google Scholar 

  19. Hsieh BT, Hsieh JF, Tsai SC et al (1999) Rhenium-188-labeled DTPA: a new radiopharmaceutical for intravascular radiation therapy. Nucl Med Biol 26:967–972

    Article  PubMed  CAS  Google Scholar 

  20. Eriksson JE, Dechat T, Grin B et al (2009) Introducing intermediate filaments: from discovery to disease. J Clin Invest 119:1763–1771

    Article  PubMed  CAS  Google Scholar 

  21. Meyer JM, Nowak B, Schuermann K et al (2003) Inhibition of neointimal proliferation with 188Re-labeled self-expanding nitinol stent in a sheep model. Radiology 229:847–854

    Article  PubMed  Google Scholar 

  22. Fareh J, Martel R, Kermani P, Leclerc G (1999) Cellular effects of beta-particle delivery on vascular smooth muscle cells and endothelial cells: a dose-response study. Circulation 99:1477–1484

    PubMed  CAS  Google Scholar 

  23. Albiero R, Nishida T, Adamian M et al (2000) Edge restenosis after implantation of high activity 32P radioactive beta-emitting stents. Circulation 101:2454–2457

    PubMed  CAS  Google Scholar 

  24. Kotzerke J, Gertler R, Buchmann I et al (2000) Different radiosensitivity of smooth muscle cells and endothelial cells in vitro as demonstrated by irradiation from a Re-188 filled balloon catheter. Atherosclerosis 152:35–42

    Article  PubMed  CAS  Google Scholar 

  25. van Tongeren RB, van Sambeek MR, van Overhagen H et al (2005) Endovascular brachytherapy for the prevention of restenosis after femoropopliteal angioplasty. Results of the VARA trial. J Cardiovasc Surg 46:437–443

    Google Scholar 

  26. Hall EJ, Miller RC, Brenner DJ (1999) Radiobiological principles in intravascular irradiation. Cardiovasc Radiat Med 1:42–47

    Article  PubMed  CAS  Google Scholar 

  27. Henning E, Dittmann H, Wiskirchen J et al (2004) Dose dependent effects of the combined beta-gamma-emitter 188rhenium on the growth of human vessel wall cells. Rofo 176:404–408

    PubMed  CAS  Google Scholar 

  28. Kehlbach R, Dittmann H, Schmid T et al (2006) Early effects of rhenium-188 treatment on proliferation, migration, and matrix synthesis of cultured human aortic smooth muscle cells. Strahlenther Onkol 182:164–171

    Article  PubMed  Google Scholar 

  29. Milliat F, Francois A, Isoir M et al (2006) Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation: implication in radiation-induced vascular damages. Am J Pathol 169:1484–1495

    Article  PubMed  CAS  Google Scholar 

  30. Wiskirchen J, Dittmann H, Kehlbach R et al (2001) Rhenium-188 for inhibition of human aortic smooth muscle cell proliferation. Int J Radiat Oncol Biol Phys 49:809–815

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Alexander Sauter.

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Sauter, A., Arthasana, D., Dittmann, H. et al. In Vitro Comparison of the Antiproliferative Effects of Rhenium-186 and Rhenium-188 on Human Aortic Endothelial Cells. Cardiovasc Intervent Radiol 34, 816–823 (2011). https://doi.org/10.1007/s00270-010-0003-z

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  • DOI: https://doi.org/10.1007/s00270-010-0003-z

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