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A Hyperfluorinated Hydrophilic Molecule for Aqueous ¹⁹F MRI Contrast Media.

ABSTRACT: Fluorine-19 (¹⁹F) magnetic resonance imaging (MRI) has the potential for a wide range of in vivo applications but is limited by lack of flexibility in exogenous probe formulation. Most ¹⁹F MRI probes are composed of perfluorocarbons (PFCs) or perfluoropolyethers (PFPEs) with intrinsic properties which limit formulation options. Hydrophilic organofluorine molecules can provide more flexibility in formulation options. We report herein a hyperfluorinated hydrophilic organoflourine, ET1084, with ?24 wt. % ¹⁹F content. It dissolves in water and aqueous buffers to give solutions with ?8?M ¹⁹F. ¹⁹F MRI phantom studies at 9.4T employing a 10-minute multislice multiecho (MSME) scan sequence show a linear increase in signal-to-noise ratio (SNR) with increasing concentrations of the molecule and a detection limit of 5?mM. Preliminary cytotoxicity and genotoxicity assessments suggest it is safe at concentrations of up to 20?mM.

SUBMITTER: Tanifum EA

PROVIDER: S-EPMC6260405 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A Hyperfluorinated Hydrophilic Molecule for Aqueous 19F MRI Contrast Media.

Tanifum Eric A EA Devkota Laxman L Ngwa Conelius C Badachhape Andrew A AA Ghaghada Ketan B KB Romero Jonathan J Pautler Robia G RG Annapragada Ananth V AV

Contrast media & molecular imaging 20181112

Fluorine-19 (19F) magnetic resonance imaging (MRI) has the potential for a wide range of in vivo applications but is limited by lack of flexibility in exogenous probe formulation. Most 19F MRI probes are composed of perfluorocarbons (PFCs) or perfluoropolyethers (PFPEs) with intrinsic properties which limit formulation options. Hydrophilic organofluorine molecules can provide more flexibility in formulation options. We report herein a hyperfluorinated hydrophilic org ...[more]

PMID: 30538612

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Project description:In cancer diagnostics, magnetic resonance imaging (MRI) uses contrast agents to enhance the distinction between the target tissue and background. Several promising approaches have been developed to increase MRI sensitivity, one of which is Overhauser dynamic nuclear polarization (ODNP)-enhanced MRI (OMRI). In this study, a macromolecular construct based on human serum albumin and nitroxyl radicals (HSA-NIT) was developed using a new synthesis method that significantly increased the modification to 21 nitroxide residues per protein. This was confirmed by electron paramagnetic resonance (EPR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry. Gel electrophoresis and circular dichroism showed no significant changes in the structure of HSA-NITs, and no oligomers were formed during modification. The cytotoxicity of HSA-NITs was comparable to that of native albumin. HSA-NITs were evaluated as potential "metal-free" organic radical relaxation-based contrast agents for 1H-MRI and as hyperpolarizing contrast agents for OMRI. Relaxivities (longitudinal and transversal relaxation rates r1 and r2) for HSA-NITs were measured at different magnetic field strengths (1.88, 3, 7, and 14 T). Phantoms were used to demonstrate the potential use of HSA-NIT as a T1- and T2-weighted relaxation-based contrast agent at 3 T and 14 T. The efficacy of 1H Overhauser dynamic nuclear polarization (ODNP) in liquids at an ultralow magnetic field (ULF, B0 = 92 ± 0.8 μT) was investigated for HSA-NIT conjugates. The HSA-NITs themselves did not show ODNP enhancement; however, under the proteolysis conditions simulating cancer tissue, HSA-NIT conjugates were cleaved into lower-molecular-weight (MW) protein fragments that activate ODNP capabilities, resulting in a maximum achievable enhancement |Emax| of 40-50 and a radiofrequency power required to achieve half of Emax, P1/2, of 21-27 W. The HSA-NIT with a higher degree of modification released increased the number of spin probes upon biodegradation, which significantly enhanced the Overhauser effect. Thus, HSA-NITs may represent a new class of MRI relaxation-based contrast agents as well as novel cleavable conjugates for use as hyperpolarizing contrast agents (HCAs) in OMRI.

Dataset Information

A Hyperfluorinated Hydrophilic Molecule for Aqueous ¹⁹F MRI Contrast Media.

Publications

A Hyperfluorinated Hydrophilic Molecule for Aqueous <sup>19</sup>F MRI Contrast Media.

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