Design and Synthesis of Fluorinated Dendrimers for Sensitive ¹⁹F MRI

Abstract

To achieve high sensitivity for (19)F MRI, a class of novel dendritic molecules with multiple pseudosymmetrical fluorines was designed and efficiently synthesized. Through iterative bromination and Williamson ether synthesis under mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was conveniently prepared without performing the group protection in a convergent way. The dendrimer is characterized by a strong (19)F NMR peak and short relaxation times. Eventually, an appreciably enhanced (19)F MRI at an extremely low concentration (18.5 μM) was achieved, which demonstrated the potential utility of such dendritic molecules in highly sensitive (19)F MRI.

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High‐Signal 19F MRI Agents

“…[4] 1 9 FMRI is less developed than 1 HMRI, in part due to the need for high signal, biocompatible 19 F probe molecules. [5] Synthesis of high-symmetry fluorochemicals,s uch as perfluorocrownethers, [6] fluoropolymers, [7] and fluorinated dendrimers [8] (e.g.,F igure 1) leads to an increase in the number of magnetically equivalent fluorine nuclei for improving signal intensity.E mulsions of these fluorochemicals represent the current state-of-the-art for 19 FMRI probes which are reaching the limit of detection threshold at clinical field strengths. [2,7] However,t hese emulsions are susceptible to stability problems,p oor physicochemical properties,a nd retention in the body.…”

Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer

“…The use of 19 F-MRI in NP applications is a developing research field investigating, for example, the applicability compared to SPIONs, the efficacy of fluorinated dendrimers and multifunctional micelle-based core–shell NPs, and the detection of folate-receptor positive tumors in a 19 F/florescence-based bimodal imaging setting [331,335,336,337]. Just recently, a 19 F based nanoemulsion has been FDA approved for noninvasive clinical cell-tracking imaging [338].…”

BODIPY Dyes Bearing Multibranched Fluorinated Chains: Synthesis, Structural, and Spectroscopic Studies

“…Among noninvasive imaging techniques, 19 F‐MRI is emerging as a powerful quantitative detection modality for clinical use because it permits in‐depth in vivo detection with high spatial resolution, without the use of radioactive agents . In particular, the combination of 19 F‐MRI with fluorescence imaging (FLI) allows simultaneously in vivo tracking ( 19 F‐MRI/FLI) and ex vivo intracellular localization (FLI); thus providing in‐depth in vivo detection, higher sensitivity, and real‐time responses . Accordingly, the integration of typical characteristics of an efficient 19 F‐MRI contrast agent, that is, an appropriate number of magnetically equivalent fluorine atoms in the BODIPY core, would result in an efficient dual modality ( 19 F‐MRI/FLI) imaging agent .…”