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Hyperpolarized fumarate is a promising biosensor for carbon-13 magnetic resonance metabolic imaging. Such molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting solutions are contaminated with the catalyst, unreacted reagents, and reaction side-product molecules, and are hence unsuitable for use in vivo. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved to a desired concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow for formation of hyperpolarized fumarate at 13C polarization levels of 30-45%.

Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd‐based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI‐CEST (Magnetic Resonance Imaging ‐ Chemical Exchange Saturation Transfer) signal of intracellular proton exchanging molecules. The magnitude of the change in the CEST response reports on water cycling across the membrane. The method has been tested on Red Blood Cells and on orthotopic murine models of breast cancer with different degree of malignancy (4T1, TS/A and 168FARN). The distribution of voxels reporting on membrane permeability fits well with the cells' aggressiveness and acts as an early reporter to monitor therapeutic treatments. [ABSTRACT FROM AUTHOR]

Nuclear Magnetic Resonance allows the non-invasive detection and quantitation of metabolites to be carried out in cells and tissues. This means that that metabolic changes can be revealed without the need for sample processing and the destruction of the biological matrix. The main limitation to the application of this method to biological studies is its intrinsic low sensitivity. The introduction of hyperpolarization techniques and, in particular, of dissolution-Dynamic Nuclear Polarization (d-DNP) and ParaHydrogen Induced Polarization (PHIP) is a significant breakthrough for the field as the MR signals of molecules and, most importantly, metabolites, can be increased by some orders of magnitude. Hyperpolarized pyruvate is the metabolite that has been most widely used for the investigation of metabolic alterations in cancer and other diseases. Although d-DNP is currently the gold-standard hyperpolarization method, its high costs and intrinsically slow hyperpolarization procedure are a hurdle to the application of this tool. However, PHIP is cost effective and fast and hyperpolarized pyruvate can be obtained using the so-called Side Arm Hydrogenation approach (PHIP-SAH). The potential toxicity of a solution of the hyperpolarized metabolite that is obtained in this way is presented herein. HP pyruvate has then been used for metabolic studies on different prostate cancer cells lines (DU145, PC3, and LnCap). The results obtained using the HP metabolite have been compared with those from conventional biochemical assays. [ABSTRACT FROM AUTHOR]

Hyperpolarization of the 13C magnetic resonance signal of l-[1-13C]lactate has been obtained using the chemically based, cost-effective method called parahydrogen-induced polarization by means of side-arm hydrogenation (PHIP-SAH). Two ester derivatives of lactate were tested and the factors that determine the polarization level on the product have been investigated in detail. The metabolic conversion of hyperpolarized l-[1-13C]lactate into pyruvate has been observed in vitro using lactate dehydrogenase (LDH) and in a cells lysate. From the acquisition of a series of 13C NMR spectra, the metabolic build-up of the [1-13C]pyruvate signal has been observed. These studies demonstrate that, even if the experimental set-up used for these PHIP-SAH hyperpolarization studies is still far from optimal, the attained polarization level is already sufficient to carry out in vitro metabolic studies. [ABSTRACT FROM AUTHOR]

Purpose: The integration of nanotechnology into biomedical imaging has significantly advanced diagnostic and theranostic capabilities. However, nanoparticle detection in imaging relies on functionalization with appropriate probes. In this work, a new approach to visualize free-label nanoparticles using MRI and MRS techniques is described, consisting of detecting by 1 H CSI specific proton signals belonging to the components naturally present in most of the nanosystems used in preclinical and clinical research., Methods: Three different nanosystems, namely lipid-based micelles, liposomes, and perfluorocarbon-based nanoemulsions, were synthesized, characterized by high resolution NMR and then visualized by 1 H CSI at 300 MHz. Subsequently the best 1 H CSI performing system was administered to murine models of cancer to evaluate the possibility of tracking the nanosystem by looking at its proton associated signal. Furthermore, an in vitro comparison between 1 H CSI and 19 F MRI was carried out., Results: The study successfully demonstrates the feasibility of detecting nanoparticles using MRI/MRS without probe functionalization, employing 1 H CSI. Among the nanosystems tested, the perfluorocarbon-based nanoemulsion exhibited the highest SNR. Consequently, it was evaluated in vivo, where its detection was achievable within tumors and inflamed regions via 1 H CSI, and in lymph nodes via PRESS., Conclusions: These findings present a promising avenue for nanoparticle imaging in biomedical applications, offering potential enhancements to diagnostic and theranostic procedures. This non-invasive approach has the capacity to advance imaging techniques and expand the scope of nanoparticle-based biomedical research. Further exploration is necessary to fully explore the implications and applications of this method., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

An efficient synthesis of vinyl-[1- 13 C]pyruvate has been reported, from which 13 C hyperpolarized (HP) ethyl-[1- 13 C]pyruvate has been obtained by means of ParaHydrogen Induced Polarization (PHIP). Due to the intrinsic lability of pyruvate, which leads quickly to degradation of the reaction mixture even under mild reaction conditions, the vinyl-ester has been synthesized through the intermediacy of a more stable ketal derivative. 13 C and 1 H hyperpolarizations of ethyl-[1- 13 C]pyruvate, hydrogenated using ParaHydrogen, have been compared to those observed on the more widely used allyl-derivative. It has been demonstrated that the spin order transfer from ParaHydrogen protons to 13 C, is more efficient on the ethyl than on the allyl-esterdue to the larger J-couplings involved. The main requirements needed for the biological application of this HP product have been met, i. e. an aqueous solution of the product at high concentration (40 mM) with a good 13 C polarization level (4.8 %) has been obtained. The in vitro metabolic transformation of the HP ethyl-[1- 13 C]pyruvate, catalyzed by an esterase, has been observed. This substrate appears to be a good candidate for in vivo metabolic investigations using PHIP hyperpolarized probes., (© 2021 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

Nuclear Magnetic Resonance allows the non-invasive detection and quantitation of metabolites to be carried out in cells and tissues. This means that that metabolic changes can be revealed without the need for sample processing and the destruction of the biological matrix. The main limitation to the application of this method to biological studies is its intrinsic low sensitivity. The introduction of hyperpolarization techniques and, in particular, of dissolution-Dynamic Nuclear Polarization (d-DNP) and ParaHydrogen Induced Polarization (PHIP) is a significant breakthrough for the field as the MR signals of molecules and, most importantly, metabolites, can be increased by some orders of magnitude. Hyperpolarized pyruvate is the metabolite that has been most widely used for the investigation of metabolic alterations in cancer and other diseases. Although d-DNP is currently the gold-standard hyperpolarization method, its high costs and intrinsically slow hyperpolarization procedure are a hurdle to the application of this tool. However, PHIP is cost effective and fast and hyperpolarized pyruvate can be obtained using the so-called Side Arm Hydrogenation approach (PHIP-SAH). The potential toxicity of a solution of the hyperpolarized metabolite that is obtained in this way is presented herein. HP pyruvate has then been used for metabolic studies on different prostate cancer cells lines (DU145, PC3, and LnCap). The results obtained using the HP metabolite have been compared with those from conventional biochemical assays., (Copyright © 2020 Cavallari, Carrera, Di Matteo, Bondar, Aime and Reineri.)

The kinetics of metabolic processes can be assessed, in real time by means of MR hyperpolarized (HP) metabolites. [1- 13 C]pyruvate, hyperpolarized by means of d-DNP, is, by far, the substrate most widely applied to the investigation of several pathologies characterized by deregulated glycolytic metabolic networks, including cancer. Hyperpolarization of [1- 13 C]pyruvate by means of the cost effective, fast and easy to handle PHIP-SAH (para-hydrogen induced polarization-side arm hydrogenation) method opens-up a pathway for the application of HP metabolites to a wide range of cancer-related studies. Herein, we report the first application of PHIP-SAH hyperpolarized [1- 13 C]pyruvate in the investigation of upregulated glycolysis in two murine breast cancer cell lines (168FARN and 4T1). The results obtained using HP pyruvate have been validated with a conventional biochemical assay and are coherent with previously-reported lactate dehydrogenase activity measured in those cells., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hyperpolarization of the 13 C magnetic resonance signal of l-[1- 13 C]lactate has been obtained using the chemically based, cost-effective method called parahydrogen-induced polarization by means of side-arm hydrogenation (PHIP-SAH). Two ester derivatives of lactate were tested and the factors that determine the polarization level on the product have been investigated in detail. The metabolic conversion of hyperpolarized l-[1- 13 C]lactate into pyruvate has been observed in vitro using lactate dehydrogenase (LDH) and in a cells lysate. From the acquisition of a series of 13 C NMR spectra, the metabolic build-up of the [1- 13 C]pyruvate signal has been observed. These studies demonstrate that, even if the experimental set-up used for these PHIP-SAH hyperpolarization studies is still far from optimal, the attained polarization level is already sufficient to carry out in vitro metabolic studies., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar (1)H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.