REGIONAL AND ARTERIAL LOCALIZATION OF RADIOACTIVE MICROPARTICLES AFTER LOCAL-DELIVERY BY UNSUPPORTED OR SUPPORTED POROUS BALLOON CATHETERS

Catheter-mediated intramural delivery of pharmaceutical agents after a ngioplasty is a potential method to reduce postangioplasty restenosis. The efficacy of such delivery has been limited both by an incomplete initial intramural deposition of delivered agents and by rapid diffusi on of soluble agents from the site of delivery. The local delivery of microparticulate agents results in prolonged retention of material at the delivery site. Accordingly this study was designed to evaluate the complementary issue of the initial delivery efficiency and pattern of localization of microparticles after local catheter-mediated delivery with two types of porous balloons. These two types were a ''standard' ' porous balloon (PB) in which hydraulic pressure both inflated the ba lloon and infused the agents and a porous balloon with a mechanical un dergirding that permitted mechanical expansion (PB/ME) before agent in fusion. Radioactive cerium 141-labeled microparticles (11.4 mu m diame ter) were locally delivered into atherosclerotic rabbit femoral arteri es after angioplasty to test the hypothesis that use of the PB/ME appa ratus would yield enhanced intramural particle deposition and decrease d systemic administration by increased balloon-wall contact before mic roparticle infusion. Six animals underwent infusion with the PR cathet er, and seven animals underwent infusion with the PB/ME catheter. An i mage of the in vivo particle distribution was obtained with a gamma ca mera during infusion, immediately after infusion, and 1, 3, and 7 days after infusion. Tissue samples from the artery, periadventitia, thigh , calf, and foot musculature, and liver were obtained at animal death, and retained radioactivity was measured with a well counter. Micropar ticle delivery was evaluated according to two parameters: (1) the frac tional regional delivery, which is the fraction of microparticles deli vered into the region surrounding the balloon in the upper leg as meas ured by the gamma camera, and (2) the fractional intramural delivery, which is the fraction of microparticles specifically delivered into th e vascular tissue as measured by direct tissue counting. The fractiona l regional delivery was 99.9% +/- 0.1% with the PB/ME and 84.2% +/- 4. 2% with the standard PR (p = 0.008). Distal delivery of microparticles was accordingly lower after infusion with the PB/ME catheter; radioac tivity at 7 days in the foot averaged 9 +/- 4.5 counts/min/mg tissue v ersus 186 +/- 67 counts/min/mg after infusion with the PB catheter (p = 0.01). Despite this difference in systemic delivery the fractional i ntramural delivery was similar for both infusion devices. Only 0.16% /- 0.04% was deposited into the arterial wall by the PB/ME, and 0.14% +/- 0.05% was deposited by the PB (p = NS). The remaining microparticl es were found in the periadventitia and overlying musculature. Retenti on of microparticles at 7 days after the delivery exceeded 90% with ea ch catheter. In conclusion, local delivery and retention of 11.4 mu m microparticles at high concentration into and around the arterial wall is feasible but is characterized by a low intramural delivery efficie ncy (<0.17%). Most of the microparticles are rapidly delivered into th e periadventitia and overlying musculature. Therefore the selection of pharmaceutical agents or genetic material delivered locally to reduce restenosis with such catheters must take into account any effects of the chosen agents on overlying tissue.