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 gadoliniumโtetraazacyclododecane 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^โ1^s^โ1^ (R2 at 56 MHz) and for CCMV functionalized with GdDOTA were R1 = 46 and R2 = 142 mM^โ1^s^โ1^ at 61 MHz. The relaxivities per intact capsid for the genetic fusion were R1 = 36,120 and R2 = 69,144 mM^โ1^s^โ1^ (R2 at 56 MHz) and for the GdDOTA CCMV construct were R1 = 2,806 and R2 = 8,662 mM^โ1^s^โ1^ at 61 MHz. The combination of high relaxivity, stable Gd^3+^ binding, and large Gd^3+^ payloads indicates the potential of viral capsids as highโperformance contrast agents. Magn Reson Med 58:871โ879, 2007. ยฉ 2007 WileyโLiss, Inc.