Minh Tam Baylatry PHARM D, MS, Abstract Co-Author: Nothing to Disclose

Homayra Ghegediban, Abstract Co-Author: Nothing to Disclose

Michel Wassef, Abstract Co-Author: Nothing to Disclose

Julien Namur PhD, Abstract Co-Author: Nothing to Disclose

Alexandre Pierre Laurent MD, PhD, Abstract Co-Author: Nothing to Disclose

Jean-Pierre Jacques Pelage MD, PhD, Presenter: Research grant, BioSphere Medical, Inc Consultant, BioSphere Medical, Inc Research grant, Biocompatibles International plc Research grant, Merit Medical Systems, Inc Consultant, Merit Medical Systems, Inc Research grant, Cook Group Incorporated Consultant, Cook Group Incorporated Research grant, Keocyt Medical Board, Keocyt Research grant, Terumo Corporation Consultant, Terumo Corporation

Bronchial artery embolization (BAE) is the first-line treatment in patients with massive hemoptysis. Recanalization of embolized arteries associated with angiogenesis may cause clinical recurrence. The use of drug-eluting beads (DEB) loaded with rapamycin (RAPA), mTOR-inhibitor with antiangiogenic effects may reduce local angiogenesis and clinical recurrence. Our objectives were to evaluate the systemic release of RAPA from DEB-RAPA, to quantify the tissular concentrations of RAPA in the lung parenchyma after BAE in an animal model and to evaluate the aspects of the bronchial arteries after embolization.

Blood and lung concentrations of RAPA released from DEB after BAE were measured in a hemodynamic sheep model of systemic hypervascularization of the lung (SHVL). SHVL was induced by selective pulmonary artery embolization (PAE) with autologous clots and fibered coils. BAE was performed 14 days after PAE in 3 sheep with 2 mL of DEB (500-700 microns) preloaded with 38 mg of RAPA. Three additional sheep underwent bland embolization of the bronchial arteries using 500-700 µ microspheres. RAPA was quantified by liquid chromatography with mass spectrometry detection in whole blood during 12 days and in the lung tissue at day 12 after sacrifice.

No peak of RAPA was observed in the blood. A steady-state concentration of RAPA in the blood was detected during the first 24 hours following BAE (median=28 ng/mL; range19-38). Beyond 24hours, RAPA levels decreased progressively to 2 ng/mL at day12. RAPA was present in lung at day12 (median=27 ng/mL; range 13-32). At pathology, one animal embolized with DEB-RAPA had extensive distal lung parenchyma necrosis. There was a trend towards reduced number of bronchial artery sections (7.0 vs 8.4) and arterial wall thickness after DEB-RAPA. Recanalization was 0% after DEB-RAPA vs 16% after bland embolization (NS).

DEB is an effective drug delivery system for RAPA allowing a sustained release and high drug levels in the lung. Further studies are required to determine the optimal RAPA dose to avoid systemic toxicity and local necrosis before definitive conclusions can be drawn. 

Drug eluting beads is an effective drug delivery system for rapamycin allowing a sustained blood release and high drug levels in the lung.

Baylatry, M, Ghegediban, H, Wassef, M, Namur, J, Laurent, A, Pelage, J, Bronchial Artery Embolization Using Rapamycin Drug-eluting Beads in an Animal Model of Lung Hypervascularization.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11011479.html