title: Embolization of hepatocellular carcinoma with drug-eluting beads: doxorubicin tissue concentration and distribution in patient liver explants.
abstract: OBJECTIVE
  To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications.
  
  
  METHODS
  Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100-300 μm, dose 75-150 mg) followed by liver transplantation at different time points (8 h to 36 days). On sections of the explanted liver, the tissue concentration of doxorubicin was determined radially around bead-occluded vessels with microspectrofluorimetry. The intra/peritumoral location of the beads and the modifications of the surrounding tissue were determined on an adjacent hematein-eosin-saffron-stained section and compared to drug measurements.
  
  
  RESULTS
  Doxorubicin was detected in the tissue surrounding the beads at all times of explantation. The drug impregnates an area of at least 1.2 mm in diameter around the occluded vessel. The tissue concentration of drug ranges from 5 μM at 8 h to 0.65 μM at 1 month. In patient transplanted at 8 h, no major tissue modification was observed and we found 42% of the beads occluding intratumoral vessels. Drug concentration was not different around intratumoral and peritumoral occluded vessels. After 9-14 days, necrosis was present around 37% of vessels and at 32-36 days, around 40% of vessels. Necrotic tissue was associated with a deeper penetration and a higher concentration of the drug than non necrotized areas, though statistically significant only at 32-36 days.
  
  
  CONCLUSIONS
  Doxorubicin-eluting beads provide a sustained delivery of drug for a period of 1 month and local tissue concentrations above cytotoxic threshold in HCC-bearing livers.
authors.affiliation: MéDIAN, UMR CNRS 6237 (MEDyC), Pharmacy University, Reims, France. namurjul@hotmail.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Namur
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Citron
authors.forename: Marty T
authors.initials: MT
authors.lastname: Sellers
authors.forename: Mark H
authors.initials: MH
authors.lastname: Dupuis
authors.forename: Michel
authors.initials: M
authors.lastname: Wassef
authors.forename: Michel
authors.initials: M
authors.lastname: Manfait
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009336:Necrosis; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004317:Doxorubicin