Early Effects of Rhenium-188 Treatment on Proliferation, Migration, and Matrix Synthesis of Cultured Human Aortic Smooth Muscle Cells

Due to its properties rhenium-188 (188Re) seems to be a promising radionuclide for stent coating to reduce restenosis following percutaneous transluminal angioplasty (PTA). In order to characterize the early effects of local 188Re treatment, human aortic smooth muscle cells (HaSMCs) were incubated with different doses of 188Re. 2 days after plating, HaSMCs were treated for a period of 5 days with 188Re. The total radiation doses applied were 1 Gy, 4 Gy, 8 Gy, 16 Gy, and 32 Gy. On days 1, 3, 5, and 7 (i.e., 2 days after the end of 188Re incubation), cell growth, clonogenic activity, cell migration, cell-cycle distribution, as well as matrix synthesis were evaluated. From the 1st day on, a dose-dependent growth inhibition was observed. Cumulative doses of ≥ 8 Gy completely inhibited colony formation. The results of the migration tests were contradictory; on day 3 the migratory activity of all treated cells was increased compared to the controls, on day 5 it was reduced. Cumulative radiation doses of ≥ 8 Gy resulted in an increased fraction of cells in G2/M-phase. The synthesis of the extracellular matrix protein tenascin was not affected by the treatment. Incubating human smooth muscle cells with 188Re for a period of 5 days (i.e., seven half-lives) results in an effective inhibition of muscle cell proliferation and colony formation. Partially, this is due to a radiation-induced G2/M-phase block. Cell migration and matrix synthesis were not effectively affected in the presented in vitro system.