LOW-DOSE, BETA-PARTICLE EMISSION FROM STENT WIRE RESULTS IN COMPLETE,LOCALIZED INHIBITION OF SMOOTH-MUSCLE CELL-PROLIFERATION

Background Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth mu scle cell (SMC) proliferation. The objective of this study was investi gate the ability of local emission of P-particles from a P-32-impregna ted titanium ''stent'' wire source to inhibit vascular SMC and endothe lial cell proliferation in cell culture and to determine the dose-resp onse characteristics of this inhibition. Methods and Results A series of experiments were performed using 0.20-mm-diameter titanium wires th at were impregnated with varying low concentrations of P-32 (activity range, 0.002 to 0.06 mu Ci/cm wire, n=47) or P-31 (nonradioactive cont rol, n=28) in cultures of rat and human aortic SMCs and in cultured bo vine aortic endothelial cells. The zone of complete cell growth inhibi tion (in millimeters from stent wire) was measured using light microsc opy in the cultures exposed to the radioactive (P-32) or control (P-31 ) wires at 6 and 12 days after plating. In both rat and human SMC cult ures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibit ion at wire activity levels greater than or equal to 0.006 mu Ci/cm. I n contrast, there was no zone of inhibition surrounding the control (P -31 impregnated) wires (P<.001 versus P-32 wires at all wire activitie s greater than or equal to 0.006 mu Ci/cm for human and rat SMCs). Pro liferating bovine endothelial cells were more radioresistant than SMCs , with no zone of inhibition observed at wire activity levels up to 0. 019 mu Ci/cm (P<.001 versus SMCs at 0.006 mu Ci/cm and 0.019 mu Ci/cm) . Conclusions We conclude that very low doses of beta-particle emissio n from a P-32-impregnated stent wire (activity levels as low as 0.006 mu Ci/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. End othelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra-arterial stent impregnated with a low conce ntration of P-32 may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation.