984-26 Prolonged Local Endovascular Drug Delivery for more than 14 Days with a New Catheter

Abstract

Tissue hyperplasia is a characteristic feature of restenotic tissue. Local application of antiproliferative drugs e.g. Photofrin II® (PFII; QLT, Canada), a photosensitive drug, might enable selective impairment of proliferating tissue by photodynamic therapy or other antiproliferative strategies. The efficacy of this therapy depends mainly on the method of drug application. Local drug delivery (LDD) consisting of six thin injection needles (31 G) that can be extended intravascular from the catheter tip laterally into periadventitial vascular tissue with was analyzed. Systemic application (2.5 mg×kg-1) and LDD (PFII, 5 mg) was performed in femoral and carotid arteries of 16 pigs after standardized vessel injury with a atherectomy device. The vessels were excised between 15 minutes and 21 days after PF II injection and fixed in liquid N2 for semiquantitative fluorescent microscopy with a reference signal. Systemic application: Intima showed a threefold higher fluorescence compared to other vessel wall layers with a maximum in all layers at 24 hours (media 50%, adventitia 85%). Maximum fluorescence (100%) was found 24 hours after injection. LDD: 95% of the applications were successful and led to a maximum fluorescence in periadventitial layers after 30 minutes (300% intima, 150% media, 380% periadventitial layer). Even after 21 days a significant PF II related fluorescence was detectable in periadventitial tissue (38%). LDD achieves a 380% higher drug content than high dose systemic application. This is the first catheter system that enables a LDD over 21 days by periadventitial depots. (supported by a grant from Friedrich Baur Stiftung No. 58/94)