pH‐Sensitive Polymethacrylates as Potential Contrast Agents in ¹⁹F MRI

Abstract

19F MRI is a promising method of diagnosis that can complement the commonly used 1H MRI with gadolinium contrast agents. Copolymers containing fluoroorganic groups demonstrate many advantages as potential 19F MRI contrast agents. In this work, a series of copolymers based on 2,2,2‐trifluoroethyl methacrylate (TFEMA), 1,1,1,3,3,3‐hexafluoroisopropyl methacrylate (HFiPMA), 2‐(dimethylamino)ethyl methacrylate (DMAEMA), or 2‐hydroxyethyl methacrylate (HEMA) units are prepared using atom transfer radical polymerization. The highest S/N values in a 19F NMR spectra is achieved with a copolymer containing 15–25 wt% TFEMA or 18–22 wt% HFiPMA. Copolymers of HFiPMA show a strong effect of pH on T1 and T2 relaxation times while only T2 is significantly affected for the TFEMA copolymers. DFT calculations reveal that the phenomenon is most likely caused by the pH‐induced changes in the distance of fluoroorganic groups within a polymer chain.

Recent Research Progress of 19F Magnetic Resonance Imaging Probes: Principle, Design, and Their Application

“…[66] However, it should be noted that the EPR concept is suffering from arguments based on the up-to-date investigation. [67] 2) Various functionalities (optical, [68] temperature, [69] pH, [70] metal, [71] redox, [72] etc., responsiveness) are easily incorporated into the polymeric 19 F MRI probes by universal chemistry methods, including organic coupling reaction, polymerization and postmodification by functional species.…”

“…[ 66 ] However, it should be noted that the EPR concept is suffering from arguments based on the up‐to‐date investigation. [ 67 ] 2) Various functionalities (optical, [ 68 ] temperature, [ 69 ] pH, [ 70 ] metal, [ 71 ] redox, [ 72 ] etc., responsiveness) are easily incorporated into the polymeric 19 F MRI probes by universal chemistry methods, including organic coupling reaction, polymerization and postmodification by functional species. 3) Chain structures, conformation and topological structures (liner, [ 73 ] dendrimer, [ 74 ] hyperbranched [ 75 ] ) of the polymeric 19 F MRI probes are able to be switched by advanced synthesis methods.…”

“…Because of the superhydrophobicity of fluorine nuclei itself, introducing the hydrophilic species next to fluorine nuclei to enhance the hydration nearby the fluorine nuclei, which is the most commonly used strategy to promote the mobility of fluorine nuclei. The hydrophilic species include 2‐hydroxyethyl methacrylate, [ 70 ] N‐(2‐hydroxypropyl)methacrylamide, [ 71 ] zwitterionic monomer (carboxybetaine monomer), [ 74 ] glycidol, [ 75 ] 2‐methyl‐2‐oxazoline, [ 78,85 ] 2‐(methylsulfinyl) ethyl acrylate (MSEA), [ 79 ] glucose, [ 77 ] β ‐cyclodextrin, [ 81 ] PEG (OEG), [ 76 ] and so on.…”

Tuning the pH of Activation of Fluorinated Hydrazone-Based Switches─A Pathway to Versatile 19F Magnetic Resonance Imaging Contrast Agents

“…Many pH-sensitive agents have been proposed for 19 F MRI such as PEGylated nanogels containing perfluorocarbons, fluorinated pyridoxine, C 6 F 6 -loaded Au-fluorescent mesoporous silica nanoparticles, or copolymers − that rely on the volume phase transition, decomposition, or isomerization as mechanisms of signal activation. Recently, we proposed molecular switches as potential 19 F MRI agents .…”

Hydrazone Molecular Switches with Paramagnetic Center as 19F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging

“…Fluorine-based MRI is well-suited for visualizing bioactive molecules or biological parameters in vivo. , It can be an important tool in the more personalized medicinal diagnosis and for understanding and rationalizing the molecular factors underlying physiological and pathological processes . For this purpose, responsive molecular MRI probes can be designed to report on various biomarkers of biological interest. , So far, several smart 19 F MRI contrast agents have been proposed, including pH-, − redox-, − Ca 2+ -, , and enzyme , -responsive agents. Among different types of stimuli, pH gradients have been frequently used as a trigger for environmentally responsive tumor imaging …”