Reduction of Tissue Hyperplasia with a Rhenium188 Mercaptoacetyltriglycine-3–filled Balloon: Preliminary Study in a Canine Urethral Model

Abstract

To evaluate the efficacy of beta-radiation therapy with rhenium-188 mercaptoacetyltriglycine-3 (MAG(3))-filled balloons to reduce tissue hyperplasia secondary to stent placement in 18 canine urethras. Eight dogs were treated with 188-Re MAG(3)-filled balloon dilation immediately after stent placement and were killed 4 weeks later (group I, n = 4) or 8 weeks later (group II, n = 4). Five dogs were treated with 188-Re MAG(3)-filled balloon dilation 2 weeks after stent placement and were killed 4 weeks after stent placement (group III). The remaining five dogs were treated with conventional balloon dilation immediately after stent placement and were killed 4 weeks later; these animals formed the control group (group IV). Retrograde urethrography (RUG) was performed during follow-up and three histologic parameters were investigated: the number of epithelial layers, papillary projection thickness, and degree of submucosal inflammatory cell infiltration. The areas inside and outside the ends of the stents were evaluated in each case after animal sacrifice. After testing statistical significance of data for RUG and histologic findings in the four study groups, the Mann-Whitney U test was used to compare groups I and II to determine delayed effects of irradiation, groups I and III to determine benefits of delayed irradiation, groups I and IV to determine efficacy of immediate irradiation for reducing tissue hyperplasia, and groups III and IV to determine efficacy of delayed irradiation for reducing tissue hyperplasia. There were no significant differences in the four study groups on RUG before animal sacrifice. Between groups I and II, group II showed significantly lower mean values in five of six histologic comparisons. Between groups I and III, group III showed significantly lower mean values in only papillary projection thickness inside the stent ends. Between groups I and IV, group I showed significantly lower mean values in all three histologic parameters outside the stent ends. Between groups III and IV, group III showed significantly lower mean values in only two histologic parameters (papillary projection thickness in the in-stent area and inflammatory cell infiltration outside the stent edges). beta-Irradiation with use of a 188-Re MAG(3)-filled balloon shows the potential to reduce tissue hyperplasia secondary to stent placement in a canine urethral model. Treatment with 188-Re MAG(3)-filled balloons at the time of stent placement shows not only favorable outcomes for reducing tissue hyperplasia but also improved delayed effects until 8 weeks.