Genome-free Viral Capsids as Carriers for Positron Emission Tomography Radiolabels

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 [ 18 F]fluorobenzaldehyde through a multistep bioconjugation strategy. An aldehyde functional gro...

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Veröffentlicht in:Molecular imaging and biology 2008-07, Vol.10 (4), p.182-191
Hauptverfasser: M. Hooker, Jacob, P. O’Neil, James, W. Romanini, Dante, E. Taylor, Scott, Francis, Matthew B.
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Sprache:eng
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Zusammenfassung: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 [ 18 F]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. [ 18 F]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.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-008-0136-5