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.
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.
Authors: Ernest W Kovacs; Jacob M Hooker; Dante W Romanini; Patrick G Holder; Katherine E Berry; Matthew B Francis Journal: Bioconjug Chem Date: 2007-06-30 Impact factor: 4.774
Authors: Chris S Rae; Ing Wei Khor; Qian Wang; Giuseppe Destito; Maria J Gonzalez; Pratik Singh; Diane M Thomas; Mayra N Estrada; Elizabeth Powell; M G Finn; Marianne Manchester Journal: Virology Date: 2005-09-26 Impact factor: 3.616
Authors: Yun-Sang Lee; Jae Min Jeong; Hyung Woo Kim; Young Soo Chang; Young Joo Kim; Mee Kyung Hong; Ganesha B Rai; Dae Yoon Chi; Won Jun Kang; Joo Hyun Kang; Dong Soo Lee; June-Key Chung; Myung Chul Lee; Young-Ger Suh Journal: Nucl Med Biol Date: 2006-06-12 Impact factor: 2.408
Authors: Sourabh Shukla; Amber L Ablack; Amy M Wen; Karin L Lee; John D Lewis; Nicole F Steinmetz Journal: Mol Pharm Date: 2012-07-09 Impact factor: 4.939