Local photodynamic therapy with Zn(II)-phthalocyanine in an experimental model of intimal hyperplasia

Photodynamic therapy (PDT) appears to be a novel promising modality to prev ent intimal hyperplasia (IH) and restenosis after angioplasty. Local PDT, t hat consists of local delivery of photosensitizing agents followed by intra luminal local irradiation, represents a recent advancement. This methodolog y requires optimization in order to achieve the best prompt outcome especia lly in terms of pharmacokinetics of the photosensitizing agent. We studied the pharmacokinetic properties by using the photosensitizing agent Zn(II)-p hthalocyanine (ZnPc), locally released by a channeled balloon. The efficacy of local PDT in reducing IH was evaluated in an experimental rabbit model of arterial injury. The maximum accumulation of ZnPc was found at 30 min: t he injured portion of the artery gave a ZnPc recovery of 1.18 mu mol/mg, as compared with undetectable amounts of ZnPc in the non injured arteries; wi thin 90 min after the local delivery, clearance of the agent was almost com plete. Local PDT produced an effective reduction of ill in our vascular inj ury model: at 7, 14, 21 and 28 days ill and intima/media ratio (IMR) was si gnificantly reduced as compared with balloon injured arteries. The local de livery of ZnPc showed favourable pharmacokinetic properties, that allow the performance of PDT immediately after the vascular injury. Local PDT perfor med in these conditions represents a promising approach to prevent IH after balloon injury. Further studies are needed to better clarify the biologica l response of the injured arterial wall to local PDT. (C) 2000 Elsevier Sci ence S.A. All rights reserved.