19F molecular MR imaging for detection of brain tumor angiogenesis: in vivo validation using targeted PFOB nanoparticles

Abstract

Molecular imaging with magnetic resonance imaging (MRI) targeted contrast agents has emerged as a promising diagnostic approach in cancer research to detect associated biomarkers. In this work, the potential of (19)F MRI was investigated to detect angiogenesis with α(ν)β(3)-targeted perfluorooctylbromide nanoparticles (PFOB NP) in a U87 glioblastoma mouse model at 7 Tesla. Mice were injected intravenously with targeted or non-targeted NP and (19)F images were immediately acquired for 90 min using a PFOB-dedicated MRI sequence. Mice infused with targeted NP exhibited higher concentrations in tumors than mice of the control group, despite the presence of nonspecific signal originating from the blood. Imaging results were corroborated by histology and fluorescence imaging, suggesting specific binding of targeted NP to α(ν)β(3) integrin. Two other groups of mice were injected 24 h before imaging to allow blood clearance but no significant differences were found between both groups, probably due to a loss of specificity of PFOB NP. This is the first demonstration of the ability of (19)F MRI to detect α(ν)β(3)-integrin endothelial expression in brain tumors in vivo.

Noninvasive Imaging of Early Venous Thrombosis by 19 F Magnetic Resonance Imaging With Targeted Perfluorocarbon Nanoemulsions

“…This might explain the low signal-to-noise ratios of recent approaches for in vivo 19 F MRI using targeted PFCs in a tumor model and after lung ischemia. 42,43 SPIT, used here to modify preformed PFCs, overcomes the problem of possible ligand destruction when linked before high-pressure homogenization. Insertion of the targeting ligand by SPIT can be performed at room temperature with gentle agitation.…”

High-Resolution Mri and Nanoparticles: the Future of Brain Imaging

“…PFC was found at the rim of the shrinking lesion even after 19 days postsurgery. More recently, Giraudeau et al used 19 F imaging to assess tumor angiogenesis based on the overexpression of integrin receptors of new vasculature [76]. The a v b 3 integrin is a well-known biomarker of neovascular proliferation and is overexpressed on activated endothelial cells [78].…”

“…Several investigators have used 19 F-based imaging strategies to look at experimental brain disease [76,77]. Flogel et al used iv.…”

“…Giraudeau et al successfully targeted brain tumor angiogenesis in a mouse model of glioblastoma at 7 T using a v b 3 -targeted perfluorooctylbormide nanoparticles. This represented the first use of 19 F MRI to detect a v b 3 -integrin expression in vivo [76].…”

Targeted nanotechnology for cancer imaging

“…Specifically, fluorine-based MRI is gaining increasing attention due to its proximity to the 1H frequency but far enough to perform ‘water-less’ MRI [197]. 19F nanoparticles have been developed and studied for use in a variety of molecular imaging [198, 199] and cell tracking applications [200, 201]. Silica-based hyperpolarized T1 agents have also been investigated as highly sensitive, background-free contrast agents for use in molecular MRI [202, 203].…”