Synthesis and Evaluation of Partly Fluorinated Block Copolymers as MRI Imaging Agents

Abstract

A series of well-defined diblock copolymers of acrylic acid with partially fluorinated acrylate and methacrylate monomers were synthesized using ATRP as potential 19F MRI imaging agents. The diblock copolymers could undergo spontaneous self-assembly in mixed and aqueous solvents to form stable micelles with a diameter from approximately 20-45 nm, having a fluorine-rich core that provides a strong signal for MRI examinations. The observed MRI image intensities were related to the NMR longitudinal and transverse relaxation times, and were found to depend on polymer structure and method of micellization. Two distinct T2 relaxation times were measured; on comparison of expected MRI image intensities with those observed experimentally, it was found that methacrylate polymers show systematically lower signal intensity than acrylate polymers. This is related to the presence of a population of nuclear spins having very short T2 relaxation times that cannot be detected under high-resolution NMR and MRI conditions.

Organic Nanoprobes for Fluorescence and 19F Magnetic Resonance Dual‐Modality Imaging

“…Alternatively, 19 F MRI holds several unique advantages such as low endogenous background signals, high signal-to-noise ratio (SNR), 100% natural isotopic abundance, relatively high sensitivity (83% of proton) and broad range of chemical shifts. [26][27][28][29] To date, some exogenous contrast agents such as molecular probes with a number of equivalent fluorine atoms, [27,[30][31][32][33][34][35] polymeric tracers containing high numbers of fluorine atoms, [28,[36][37][38][39][40][41][42] and fluorinated metallic nanoparticles [43][44][45][46] have been developed and employed for 19 F MRI. Despite great successes, it is highly desirable and still challenging to develop suitable 19 F MRI contrast agents with satisfied performance as well as multi-modalities.…”

Fluorinated Copolymer Nanoparticles for Multimodal Imaging Applications

“…[1,2,4,5,[21][22][23] The rarity of physiologic fluorine can be exploited to generate highly selective, 19 F images that can be superimposed over complimentary 1 H images, thus providing an anatomical context for the fluorinated contrast agent. [9,23,24] Research in this area has focused on the synthesis of fluorinated nanoparticles using a variety of different approaches.…”

“…Other studies have created novel fluorinated amphiphilic block copolymers that form micelles in aqueous solution. [1,4,5,27] Typically, a living free radical polymerization method is employed to synthesize such amphiphilic block copolymers. [1,5,27] This polymer self assembles in water and the resulting suspension is used as the contrast agent.…”

“…[1,4,5,27] Typically, a living free radical polymerization method is employed to synthesize such amphiphilic block copolymers. [1,5,27] This polymer self assembles in water and the resulting suspension is used as the contrast agent. Developing particles that have the ability to actively or passively target cells or tissues with specific pathologies, such as tumors, could enable one to locate tumors or other sites of inflammation with greater precision using MRI, or analyze biopsied tumor tissue using SIMS.…”

Hyperbranched polymers for in vivo multimodal molecular imaging

“…Inclusion of large quantities of these moieties in an amphiphilic material, dispersed in aqueous media, can require long image acquisition times (hours). 257,258 It has been shown that the T 2 relaxation time of these fluorinated species is a good indicator of imaging performance, and that longer T 2 times were achieved by maintaining high mobility and flexibility of fluorinated groups. [259][260][261] By copolymerising fluorinated monomers into a hyperbranched polymer with a water soluble monomer (dimethylaminomethyl methacrylate), the association of the fluorinated groups was frustrated and imaging times decreased dramatically (< 10 minutes).…”