title: Magnetic resonance imaging of major histocompatibility class II expression in the renal medulla using immunotargeted superparamagnetic iron oxide nanoparticles.
abstract: We demonstrate the development and successful application of immunotargeted superparamagnetic iron oxide nanoparticles (ITSIONs), with in vivo magnetic resonance diagnostic and potential drug delivery capability for kidney disease. Further, the versatility of the conjugation chemistry presents an attractive route to the preparation of a range of biomolecule-nanoparticle conjugates. The ITSION contrast agent is a stable, biocompatible, targeted nanoparticle complex that combines a monodisperse iron oxide nanoparticle core with a functionalized phospholipid coating conjugated to antibodies that is capable of targeting normal cells expressing specific target antigens. The plasma half-life and R1 and R2 relaxivities suggest sufficient time for targeted binding while clearing from the system quick enough for detection of specific contrast enhancement. RT1 anti-MHC Class II antibodies were used to target the renal medulla of the rat, a section of the kidney in which MHC Class II, associated with inflammation, is specifically expressed. For in vivo resonance imaging, we compare phospholipid coated nanoparticles, nonspecific ITSIONs, and RT1 ITSIONs. Enhanced binding of the RT1 ITSIONS indicates specificity for the renal medulla and thus potential for disease detection or drug delivery.
authors.affiliation: Department of Applied Physics, Columbia University, 200 SW Mudd Building, New York, New York 10027, USA.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Hultman
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Raffo
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Grzenda
authors.forename: Paul E
authors.initials: PE
authors.lastname: Harris
authors.forename: Truman R
authors.initials: TR
authors.lastname: Brown
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling / Q000379:methods*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007089:Image Enhancement / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods; D007679:Kidney Medulla / Q000033:anatomy & histology* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008280:Magnetics / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D000949:Histocompatibility Antigens Class II; C000499:ferric oxide