title: Viral capsids as MRI contrast agents.
abstract: Viral capsids have the potential for combined cell/tissue targeting, drug delivery, and imaging. Described here is the development of a viral capsid as an efficient and potentially relevant MRI contrast agent. Two approaches are outlined to fuse high affinity Gd(3+) chelating moieties to the surface of the cowpea chlorotic mottle virus (CCMV) capsid. In the first approach, a metal binding peptide has been genetically engineered into the subunit of CCMV. In a second approach gadolinium-tetraazacyclododecane tetraacetic acid (GdDOTA) was attached to CCMV by reactions with endogenous lysine residues on the surface of the viral capsid. T(1) and T(2) ionic relaxivity rates for the genetic fusion particle were R1 = 210 and R2 = 402 mM(-1)s(-1) (R2 at 56 MHz) and for CCMV functionalized with GdDOTA were R1 = 46 and R2 = 142 mM(-1)s(-1) at 61 MHz. The relaxivities per intact capsid for the genetic fusion were R1 = 36,120 and R2 = 69,144 mM(-1)s(-1) (R2 at 56 MHz) and for the GdDOTA CCMV construct were R1 = 2,806 and R2 = 8,662 mM(-1)s(-1) at 61 MHz. The combination of high relaxivity, stable Gd(3+) binding, and large Gd(3+) payloads indicates the potential of viral capsids as high-performance contrast agents.
authors.affiliation: Center for BioInspired Nanomaterials, Montana State University, Bozeman, Montana 59717, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Liepold
authors.forename: Stasia
authors.initials: S
authors.lastname: Anderson
authors.forename: Deborah
authors.initials: D
authors.lastname: Willits
authors.forename: Luke
authors.initials: L
authors.lastname: Oltrogge
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Frank
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
authors.forename: Mark
authors.initials: M
authors.lastname: Young
mesh_terms: D017795:Bromovirus; D002213:Capsid; D003287:Contrast Media; D006571:Heterocyclic Compounds; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate