200 A Novel Retrievable Drug Infusion Stent and Blood Brain Barrier Portal for Neurooncologic Therapies

INTRODUCTION: The blood brain barrier (BBB) is prohibitive to intravascular drug delivery and has restricted spinal cord drug delivery of therapies to intrathecal approaches. METHODS: A dumbbell shaped, retrievable drug infusion stentgraft (RDIS) was constructed from nitinol and polytetrafluoroethylene. Seven anesthetized pigs underwent percutaneous femoral insertion of the sheathed RDIS and deployment in the lower thoracic aorta by sheath withdrawal. Anti-glial fibrillary acidic protein (GFAP) antibody was instilled to the outer chamber for 30 minutes +/- histamine 0.08 mg followed by stent recovery by sheath advancement, spinal cord explant and staining with Alexafluor 647 secondary and measurement of fluorescent intensity (FI). RESULTS: The stentgraft was delivered into the thoracic aorta by sheath withdrawal. Angiography confirmed center lumen distal perfusion while an integrated cannula allows infusion from outs ide the patient to the isolated outer chamber and intercostals. Animals treated with histamine and GFAP (n=4) revealed increased FI (mean 1099.60 +/- 172.14) compared to animal without histamine (n=3, 652.51 +/- 187.43), p < 0.001. Histamine delivered in a focal dose, caused only a brief decline in blood pressure that resolved in under 2 minutes. Although the stent perfused only 2-3 sets of intercostals, positive staining was observed well into the adjacent upper thoracic and lumbar spinal cord. CONCLUSIONS: An RDIS achieves focal drug delivery of antibody to the spinal cord and is retrievable after use, while a histamine portal facilitates passage across the BBB. The RDIS may have future utility for vascular based delivery of antibody therapeutics or other macromolecules to the spinal cord for oncologic, spinal cord injury and neurodegenerative disease while minimizing drug at the systemic level.