title: Noninvasive monitoring of local drug release in a rabbit radiofrequency (RF) ablation model using X-ray computed tomography.
abstract: In this study, X-ray computed tomography (CT) was utilized as a noninvasive method to directly examine local drug release kinetics in livers before and following radiofrequency thermal ablation. Iohexol, a CT contrast agent, was used as a drug-mimicking molecule. Release of iohexol in healthy and ablated rabbit livers over 48 h was quantified and correlated with the release profiles from phosphate-buffered saline (PBS) in vitro. The results show that iohexol release in ablated livers is significantly slower than both release in normal livers and in vitro. The time at which 50% of the drug was released (t(1/2)) into ablated liver (20.6+/-5.9 h) was 1.7 times longer than in normal liver (12.1+/-5.4 h) and approximately two times longer than that in PBS (10.1+/-1.2 h). The slower release in ablated livers is a result of severe tissue damage inflicted by thermal ablation, as supported by histological examination. This data suggests that a noninvasive imaging method provides a superior measurement over in vitro release studies in accurately quantifying the local release kinetics of an agent in an altered physiological system in vivo. Because the development of a successful local drug therapy is dependent on the understanding of the agent release kinetics at the implantation site, the noninvasive data may be indispensable in effectively predicting the implant behavior in a physiological system.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Szymanski-Exner
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Stowe
authors.forename: Roee S
authors.initials: RS
authors.lastname: Lazebnik
authors.forename: Kyle
authors.initials: K
authors.lastname: Salem
authors.forename: David L
authors.initials: DL
authors.lastname: Wilson
authors.forename: John R
authors.initials: JR
authors.lastname: Haaga
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D017115:Catheter Ablation / Q000295:instrumentation / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D007472:Iohexol / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D011817:Rabbits; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D007472:Iohexol