Virus-based nanomaterials as positron emission tomography and magnetic resonance contrast agents: from technology development to translational medicine.

Viruses have recently emerged as ideal protein scaffolds for a new class of contrast agents that can be used in medical imaging procedures such as positron emission tomography (PET) and magnetic resonance imaging (MRI). Whereas synthetic nanoparticles are difficult to produce as homogeneous formulations due to the inherently stochastic nature of the synthesis process, virus-based nanoparticles are genetically encoded and are therefore produced as homogeneous and monodisperse preparations with a high degree of quality control. Because the virus capsids have a defined chemical structure that has evolved to carry cargoes of nucleic acids, they can be modified to carry precisely defined cargoes of contrast agents and can be decorated with spatially defined contrast reagents on the internal or external surfaces. Viral nanoparticles can also be genetically programed or conjugated with targeting ligands to deliver contrast agents to specific cells, and the natural biocompatibility of viruses means that they are cleared rapidly from the body. Nanoparticles based on bacteriophages and plant viruses are safe for use in humans and can be produced inexpensively in large quantities as self-assembling recombinant proteins. Based on these considerations, a new generation of contrast agents has been developed using bacteriophages and plant viruses as scaffolds to carry positron-emitting radioisotopes such as [(18) F] fluorodeoxyglucose for PET imaging and iron oxide or Gd(3+) for MRI. Although challenges such as immunogenicity, loading efficiency, and regulatory compliance remain to be address, virus-based nanoparticles represent a promising new enabling technology for a new generation of highly biocompatible and biodegradable targeted imaging reagents.