Genome-free Viral Capsids as Carriers for Positron Emission Tomography Radiolabels
- Jacob M. HookerAffiliated withDepartment of Chemistry, University of California
- , James P. O’NeilAffiliated withDepartment of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory
- , Dante W. RomaniniAffiliated withDepartment of Chemistry, University of California
- , Scott E. TaylorAffiliated withDepartment of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory
- , Matthew B. FrancisAffiliated withDepartment of Chemistry, University of CaliforniaMaterials Sciences Division, Lawrence Berkeley National Labs Email author
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We have developed a modular synthetic strategy to append imaging agents to a viral capsid.
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.
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.
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.
Key wordsVirus PET Oxime Bioconjugation F-18
- Genome-free Viral Capsids as Carriers for Positron Emission Tomography Radiolabels
Molecular Imaging and Biology
Volume 10, Issue 4 , pp 182-191
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- 1. Department of Chemistry, University of California, Berkeley, CA, 94720-1460, USA
- 2. Department of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA
- 3. Materials Sciences Division, Lawrence Berkeley National Labs, Berkeley, CA, 94720, USA