Fluorine polymer probes for magnetic resonance imaging: quo vadis?

Abstract

Over the last few years, the development and relevance of 19 F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of 19 F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of 19 F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.

Internal Structure of Thermoresponsive Physically Crosslinked Nanogel of Poly[N-(2-hydroxypropyl)methacrylamide]-Block-Poly[N-(2,2-difluoroethyl)acrylamide], Prominent 19F MRI Tracer

“…Magnetic resonance imaging (MRI) is a well-established non-invasive diagnostic method. The most widely used proton 1 H MRI has found a vast range of applications clinically and in research, but certain anatomical and/or pathological structures are hard or impossible to visualise [ 1 , 2 , 3 ]. To overcome this problem, a T 1 (or less commonly T 2 ) contrast agent (CA) can be employed as they accumulate in certain tissues and alter their relaxation properties, thus enabling their visualisation.…”

“…Nevertheless, 19 F MRI small-molecule tracers suffer from strong fluorophilicity, leading to excessive hydrophobicity, which often causes an unfavourable biodistribution in the human body. This problem can be overcome by using macromolecular fluorinated tracers, whose biodistribution can be tailored to the required application by varying the polymer composition and architecture [ 3 , 10 , 11 , 12 , 13 ].…”

“…In our previous research, we described self-assembled nanoparticles with similar properties, which were based on thermoresponsive diblock copolymers. These copolymers were composed of a hydrophilic poly[ N -(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMOX) block and a thermoresponsive poly[ N -(2,2-difluoroethyl)acrylamide] (PDFEA) block [ 3 , 10 , 12 ]. PHPMA is well known for its excellent biocompatibility and ability to hide nanoparticles from the immune system (the “stealth” effect) [ 36 ], and the PMOX shows similar if not better properties in this regard [ 37 ].…”

Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-β Detection

“…To eliminate this issue, increasing the amount of magnetically equivalent fluorine atoms per molecule is needed. This can be done either through attaching additional CF3 groups to the probe or through conjugating the probe to perfluorinated macromolecules, which are currently used to track the cell activity in vivo using MRI [ 110 , 111 ]. A higher affinity of fluorescence probes allows the reduction of the background signal due to nonspecific binding and, therefore, tends to increase the signal-to noise-ratio (SNR).…”

Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer’s Disease

“…However, ionic gadolinium complexes can leak toxic Gd 3+ ions with short half-life and it has been reported that Gd 3+ chelates can lead to renal insufficiency (Rashid et al, 2016;Marasini et al, 2020). Fluorinated small molecules that bind to amyloid plaques can be detected by 19 F MRI (Jirak et al, 2019). But for their low in vivo concentrations, this method might be difficult to be applied to human clinical medicine (Sillerud et al, 2013).…”