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Purpose: We have developed a modular synthetic strategy to append imaging agents to a viral capsid.Procedures: The hollow protein shell of bacteriophage MS2 (mtMS2) was labeled on its inside surface with [18F]fluorobenzaldehyde through a multistep bioconjugation strategy. An aldehyde functional group was first attached to interior tyrosine residues through a diazonium coupling reaction. The aldehyde was further elaborated to an alkoxyamine functional group, which was then condensed with n.c.a. [18F]fluorobenzaldehyde. Biodistribution of the radioactive MS2 conjugates was subsequently evaluated in Sprague-Dawley rats.Results: Relative to fluorobenzaldehyde, fluorine-18-labeled MS2 exhibited prolonged blood circulation time and a significantly altered excretion profile. It was also observed that additional small molecule cargo installed inside the capsids did not alter the biodistribution.Conclusions: These studies provide further insight into the pharmacokinetic behavior of nanomaterials and serve as a platform for the future development of targeted imaging and therapeutic agents based on mtMS2. [ABSTRACT FROM AUTHOR]

Two high-relaxivity nanoscale magnetic resonance contrast agents have been built using bacteriophage MS2 as a biomolecular scaffold. Protein capsid shells were functionalized on either the exterior or interior surface to display multiple copies of an aldehyde functional group. Subsequently, ∼90 heteropodal bis(hydroxypyridonate)terephthalamide ligands were attached to these sites through oxime condensation reactions. Upon complexation with Gd3, contrast agents with ionic relaxivities of up to 41.6 mM-1s-1(30 MHz, 25 °C) and total molecular relaxivities of up to 3900 mM-1s-1(30 MHz, 25 °C) were produced. Capsids sequestering the Gd-chelates on the interior surface (attached through tyrosine residues) not only provided higher relaxivities than their exterior functionalized counterparts (which relied on lysine modification) but also exhibited improved water solubility and capsid stability. The attachment functional cargo to the interior surface is envisioned to minimize its influences on biodistribution, yielding significant advantages for tissue targeting by additional groups attached to the capsid exterior. [ABSTRACT FROM AUTHOR]