title: Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging.
abstract: Contrast agents targeted to molecular markers of disease are currently being developed with the goal of identifying disease early and evaluating treatment effectiveness using noninvasive imaging modalities such as MRI. Pharmacokinetic profiling of the binding of targeted contrast agents, while theoretically possible with MRI, has thus far only been demonstrated with more sensitive imaging techniques. Paramagnetic liquid perfluorocarbon nanoparticles were formulated to target alpha(v)beta(3)-integrins associated with early atherosclerosis in cholesterol-fed rabbits to produce a measurable signal increase on magnetic resonance images after binding. In this work, we combine quantitative information of the in vivo binding of this agent over time obtained by means of MRI with blood sampling to derive pharmacokinetic parameters using simultaneous and individual fitting of the data to a three compartment model. A doubling of tissue exposure (or area under the curve) is obtained with targeted as compared to control nanoparticles, and key parameter differences are discovered that may aid in development of models for targeted drug delivery.
authors.affiliation: Consortium for Translational Research in Advanced Imaging and Nanomedicine, Washington University, St Louis, Missouri 63108, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Neubauer
authors.forename: Hoon
authors.initials: H
authors.lastname: Sim
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Winter
authors.forename: Shelton D
authors.initials: SD
authors.lastname: Caruthers
authors.forename: Todd A
authors.initials: TA
authors.lastname: Williams
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.forename: David
authors.initials: D
authors.lastname: Sept
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics; D005682:Gadolinium / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling / Q000379:methods; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D015336:Molecular Probe Techniques; D053758:Nanoparticles; D011817:Rabbits
chemical_list: D003287:Contrast Media; D039302:Integrin alphaVbeta3; D005682:Gadolinium