The promising dynamic nuclear polarization (DNP) for hyperpolarized (13)C-MRI/MRS of real-time metabolism in vivo is challenged by the limited number of agents with the required physical and biological properties. The physical requirement of a liquid-state T(1) of tens of seconds is mostly found for (13)C-carbons in small molecules that have no direct protons attached, i.e. carbonyl, carboxyl and certain quaternary carbons. Unfortunately, such carbon positions do not exist in a large number of metabolic agents, and chemical shift dispersion often limits detection of their chemical evolution. We have previously shown that direct deuteration of protonated carbon positions significantly prolongs the (13)C T(1) in the liquid state and provides potential (13)C-labeled agents with differential chemical shift with respect to metabolism. The Choline Molecular Probe [1,1,2,2-D(4), 2-(13)C]choline chloride (CMP2) has recently been introduced as a means of studying choline metabolism in a hyperpolarized state. Here, the biophysical properties of CMP2 were characterized and compared with those of [1-(13)C]pyruvate to evaluate the impact of molecular probe deuteration. The CMP2 solid-state polarization build-up time constant (30 min) and polarization level (24%) were comparable to those of [1-(13)C]pyruvate. Both compounds' liquid state T(1) increased with temperature. The high-field T(1) of CMP2 compared favorably with [1-(13)C]pyruvate. Thus, a deuterated agent demonstrated physical properties comparable to a hyperpolarized compound of already proven value, whereas both showed chemical shift dispersion that allowed monitoring of their metabolism. It is expected that the use of deuterated carbon-13 positions as reporting hyperpolarized nuclei will substantially expand the library of agents for DNP-MR.

Inorganic nanocrystals (NCs) have been extensively developed for a variety of uses. The ability to obtain high-resolution NMR signals from the core nuclei of NCs in solution could offer new opportunities in materials sciences and MR imaging. Herein, we demonstrate that small, water-soluble F-ionic NCs can average out homonuclear dipolar interactions, enabling one to obtain high-resolution F NMR signals in solution that reflect the MR properties of F in the crystal core. Decorating F-NC surfaces with a biocompatible poly(ethylene glycol) coating maintains colloidal stability in water while preserving the NC high-resolution F NMR properties, even after further functionalization. The high content and magnetic equivalence of the fluorides within the NCs enable their use as imaging tracers for in vivo F MRI by facilitating a "hot-spot" display of their distribution.

A new noninvasive, nonradioactive approach for glucose imaging using spin hyperpolarization technology and stable isotope labeling is presented. A glucose analog labeled with (13)C at all six positions increased the overall hyperpolarized imaging signal; deuteration at all seven directly bonded proton positions prolonged the spin-lattice relaxation time. High-bandwidth (13)C imaging overcame the large glucose carbon chemical shift dispersion. Hyperpolarized glucose images in the live rat showed time-dependent organ distribution patterns. At 8 s after the start of bolus injection, the inferior vena cava was demonstrated at angiographic quality. Distribution of hyperpolarized glucose in the kidneys, vasculature, and heart was demonstrated at 12 and 20 s. The heart-to-vasculature intensity ratio at 20 s suggests myocardial uptake. Cancer imaging, currently performed with (18)F-deoxyglucose positron emission tomography (FDG-PET), warrants further investigation, and glucose imaging could be useful in a vast range of clinical conditions and research fields where the radiation associated with the FDG-PET examination limits its use.

Nature-inspired nanosized formulations based on an imageable, small-sized inorganic core scaffold, on which biomolecules are assembled to form nanobiomimetics, hold great promise for both early diagnostics and developed therapeutics. Nevertheless, the fabrication of nanobiomimetics that allow noninvasive background-free mapping of pathological events with improved sensitivity, enhanced specificity, and multiplexed capabilities remains a major challenge. Here, we introduce paramagnetic glyconanofluorides as small-sized (<10 nm) glycomimetics for immunotargeting and sensitive noninvasive in vivo 19 F magnetic resonance imaging (MRI) mapping of inflammation. A very short T 1 relaxation time (70 ms) of the fluorides was achieved by doping the nanofluorides' solid crystal core with paramagnetic Sm 3+ , resulting in a significant 8-fold enhancement in their 19 F MRI sensitivity, allowing faster acquisition and improved detectability levels. The fabricated nanosized glycomimetics exhibit significantly enhanced uptake within activated immune cells, providing background-free in vivo mapping of inflammatory activity, demonstrated in both locally induced inflammation and clinically related neuropathology animal models. Fabricating two types of nanofluorides, each with a distinct chemical shift, allowed us to exploit the color-like features of 19 F MRI to map, in real time, immune specificity and preferred targetability of the paramagnetic glyconanofluorides, demonstrating the approach's potential extension to noninvasive multitarget imaging scenarios that are not yet applicable for nanobiomimetics based on other nanocrystal cores.