Polymeric ¹⁹F MRI Contrast Agents Prepared by Ring-Opening Metathesis Polymerization/Dihydroxylation

Abstract

The capability of ring-opening metathesis polymerization (ROMP) to efficiently incorporate bulky monomers and conserve olefin bonds during polymerization was exploited to design water-soluble fluoropolymers, which were evaluated as potential quantitative 19 F magnetic resonance imaging (MRI) contrast agents. The fluoromonomeric units were comprised of either 3, 6, 9 or 18 magnetically equivalent fluorine atoms.Aqueous solubility was achieved through dihydroxylation of the partially unsaturated polymeric backbone and by either TEG-based linker incorporation, ammonium quaternization or copolymerization.

Superfluorinated, Highly Water-Soluble Polyphosphazenes as Potential 19F Magnetic Resonance Imaging (MRI) Contrast Agents

“…In addition, X-nuclei MRI can provide fundamental, new metabolic information related to cellular energetic metabolism and ion homeostasis in tissues that cannot be assessed using standard proton MRI. In particular, 19 F has numerous attractive properties, such as 100% natural abundance and a negligible 19 F background signal in tissues, prompting extensive research into 19 F-MRI probes [13]. In addition, it allows for quantitative detection of distinct molecular targets in vivo due to the broad chemical shift range in nuclear magnetic resonance (NMR) of various organofluorine species applied as signal enhancers for 19 F-MRI [14].…”

“…In particular, 19 F has numerous attractive properties, such as 100% natural abundance and a negligible 19 F background signal in tissues, prompting extensive research into 19 F-MRI probes [13]. In addition, it allows for quantitative detection of distinct molecular targets in vivo due to the broad chemical shift range in nuclear magnetic resonance (NMR) of various organofluorine species applied as signal enhancers for 19 F-MRI [14]. Thereby, 19 F-MRI is an emerging modality, predominantly for spectral molecular imaging and cell tracking.…”

“…In addition, it allows for quantitative detection of distinct molecular targets in vivo due to the broad chemical shift range in nuclear magnetic resonance (NMR) of various organofluorine species applied as signal enhancers for 19 F-MRI [14]. Thereby, 19 F-MRI is an emerging modality, predominantly for spectral molecular imaging and cell tracking. However, the sensitivity of 19 F-MRI remains a challenge, as the local 19 F concentration cannot come close to the 1 H content present in the human body.…”

Biodegradable Polyphosphoester Micelles Act as Both Background-free 31P Magnetic Resonance Imaging Agents and Drug Nanocarriers

“…17 Current approaches focus on the synthesis of 19 F MRI agents with improved properties. 13,[18][19][20][21][22][23] Our solution introduces biocompatible, biodegradable polymers that can be imaged via 31 P-nucleus instead of common 19 F, which we realized by tailoring the structural properties of phosphorus-containing polymers to overcome the unfavorable magnetic resonance properties of 31 P. 31 P is the natural, 100 % abundant, NMR-active isotope of phosphorus. However, the development of background-free 31 P MRI agents has been hampered by several factors, including the intrinsic background from natural phosphates, the low gyromagnetic ratio with resulting low sensitivity of 31 P 7 % compared to proton, and other unfavorable MR characteristics.…”

Fluorinated Polymer Zwitterions: Choline Phosphates and Phosphorylcholines

“…Like hydrophilic polymers, fluorinated polymers tend toward nonfouling surface properties, but for reasons associated with surface energy rather than hydrophilicity. , Using fluorinated polymers in water is of interest biologically for 19 F magnetic resonance imaging ( 19 F MRI) contrast agents (CAs), though aggregation of the fluorinated units in water is problematic due to depletion of the signal. Recent activity along these lines is highlighted by the preparation of water-soluble fluorinated sulfoxide polymers, as well as fluorinated poly­(2-oxazoline) with favorable MRI contrast properties. − Perfluorocarbons, such as perfluorobutane (PFB) and perfluoro- n -octyl bromide (PFOB), are commonly used as CAs for 19 F MRI and ultrasound imaging. Encapsulation of perfluorocarbons as the oil phase in emulsions requires small molecule or polymer surfactants, some of the most interesting of which are themselves fluorinated amphiphilic polymers. − Moreover, fluorinated polymers are used as antifouling coatings with low surface energies that promote foulant release …”