title: Drug uptake in a rodent sarcoma model after intravenous injection or isolated lung perfusion of free/liposomal doxorubicin.
abstract: The distribution of free and liposomal doxorubicin (Liporubicin) administered by intravenous injection (IV) or isolated lung perfusion (ILP) was compared in normal and tumor tissues of sarcoma bearing rodent lungs. A single sarcomatous tumor was generated in the left lung of 35 Fischer rats, followed 10 days later by left-sided ILP (n=20) or IV drug administration (n=12), using 100 microg and 400 microg free or liposomal doxorubicin, respectively. The tumor and lung tissue drug concentration was measured by HPLC. Free doxorubicin administered by ILP resulted in a three-fold (100 microg) and 10-fold (400 microg) increase of the drug concentration in the tumor and normal lung tissue compared to IV administration. In contrast, ILP with Liporubicin resulted in a similar drug uptake in the tumor and lung tissue compared to IV injection. For both drug formulations and dosages, ILP resulted in a higher tumor to lung tissue drug ratio but also in a higher spatial heterogeneity of drug distribution within the lung compared to IV administration. ILP resulted in a higher tumor to lung tissue drug ratio and in a more heterogeneous drug distribution within the lung compared to IV drug administration.
authors.affiliation: Division of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Cai
authors.initials: C
authors.lastname: Cheng
authors.forename: Amina
authors.initials: A
authors.lastname: Haouala
authors.forename: Thorsten
authors.initials: T
authors.lastname: Krueger
authors.forename: Francois
authors.initials: F
authors.lastname: Mithieux
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Perentes
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Decosterd
authors.forename: Hans-Beat
authors.initials: HB
authors.lastname: Ris
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism*; D007275:Injections, Intravenous; D008081:Liposomes; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344; D012509:Sarcoma / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin