title: Local carboplatin delivery and tissue distribution in livers after radiofrequency ablation.
abstract: This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, USA.
authors.forename: A
authors.initials: A
authors.lastname: Szymanski-Exner
authors.forename: A
authors.initials: A
authors.lastname: Gallacher
authors.forename: N T
authors.initials: NT
authors.lastname: Stowe
authors.forename: B
authors.initials: B
authors.lastname: Weinberg
authors.forename: J R
authors.initials: JR
authors.lastname: Haaga
authors.forename: J
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D016190:Carboplatin / Q000378:metabolism / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000528:radiation effects; D011846:Radio Waves; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin