PET Imaging and Biodistribution of Chemically Modified Bacteriophage MS2

Abstract

The fields of nanotechnology and medicine have merged in the development of new imaging and drug delivery agents based on nanoparticle platforms. As one example, a mutant of bacteriophage MS2 can be differentially modified on the exterior and interior surfaces for the concurrent display of targeting functionalities and payloads, respectively. In order to realize their potential for use in in vivo applications, the biodistribution and circulation properties of this class of agents must first be investigated. A means of modulating and potentially improving the characteristics of nanoparticle agents is the appendage of PEG chains. Both MS2 and MS2-PEG capsids possessing interior DOTA chelators were labeled with (64)Cu and injected intravenously into mice possessing tumor xenografts. Dynamic imaging of the agents was performed using PET-CT on a single animal per sample, and the biodistribution at the terminal time point (24 h) was assessed by gamma counting of the organs ex vivo for 3 animals per agent. Compared to other viral capsids of similar size, the MS2 agents showed longer circulation times. Both MS2 and MS2-PEG bacteriophage behaved similarly, although the latter agent showed significantly less uptake in the spleen. This effect may be attributed to the ability of the PEG chains to mask the capsid charge. Although the tumor uptake of the agents may result from the enhanced permeation and retention (EPR) effect, selective tumor imaging may be achieved in the future by using exterior targeting groups.

Stealth filaments: Polymer chain length and conformation affect the in vivo fate of PEGylated potato virus X

“…[60, 62–65] For example, 30 nm-sized icosahedrons CPMV and phage Qβ predominantly accumulate in the liver, while 300x18 nm rod TMV, 30 nm-sized phage MS2, and 900x6 nm filamentous phage M13 were found in both the liver and spleen. [60, 62–65] Of note, a different biodistribution pattern was observed for the 30 nm-sized plant virus cowpea chlorotic mottle virus (CCMV) with much of the administered dose accumulating in the thyroid. [66]…”

Design of virus-based nanomaterials for medicine, biotechnology, and energy

“…It has been utilized for ascertaining the biodistribution of non-PEGylated 209 and PEGylated 210 MS2 capsids through incorporation of [ 18 F]fluorobenzaldehyde and 64 Cu chelated with DOTA, respectively. Taking it a step further, biodistribution of encapsulated or non-encapsulated superparamagnetic iron oxide nanoparticles, 18 F, and poly-L-lysine (PLL) cation (for packaging 18 F) within hemagglutinating virus of Japan envelopes (HVJ-Es) was studied to determine whether magnetic stimulus can be used to redirect the viruses to the head, and it was clear that the application of the magnets altered the fate of the viruses, with increased signal in the head.…”

Understanding the enormous diversity of bacteriophages: The tailed phages that infect the bacterial family Enterobacteriaceae

“…In addition, phage virions and related particles are being developed as nanocontainers for specific chemical cargoes that can be delivered to specific targets ( e.g. , Nam et al , 2006; Lee et al , 2009; Shen et al , 2010; Cardinale et al , 2012; Hyman, 2012; Culpepper et al , 2013; Farkas et al , 2013; Farr et al , 2013; Kale et al , 2013; Qazi et al , 2013). …”