Mesoporous silica-coated hollow manganese oxide (HMnO@mSiO₂) nanoparticles were developed as a novel T₁ magnetic resonance imaging (MRI) contrast agent. We hypothesized that the mesoporous structure of the nanoparticle shell enables optimal access of water molecules to the magnetic core, and consequently, an effective longitudinal (R₁) relaxation enhancement of water protons, which value was measured to be 0.99 (mM⁻¹s⁻¹) at 11.7 T. Adipose-derived mesenchymal stem cells (MSCs) were efficiently labeled using electroporation, with much shorter T₁ values as compared to direct incubation without electroporation, which was also evidenced by signal enhancement on T₁-weighted MR images in vitro. Intracranial grafting of HMnO@mSiO₂-labeled MSCs enabled serial MR monitoring of cell transplants over 14 days. These novel nanoparticles may extend the arsenal of currently available nanoparticle MR contrast agents by providing positive contrast on T₁-weighted images at high magnetic field strengths.

Amyloid fibrils are self-assembled filamentous structures associated with protein deposition conditions including Alzheimer's disease and the transmissible spongiform encephalopathies. Despite the immense medical importance of amyloid fibrils, no atomic-resolution structures are available for these materials, because the intact fibrils are insoluble and do not form diffraction-quality 3D crystals. Here we report the high-resolution structure of a peptide fragment of the amyloidogenic protein transthyretin, TTR(105–115), in its fibrillar form, determined by magic angle spinning NMR spectroscopy. The structure resolves not only the backbone fold but also the precise conformation of the side chains. Nearly complete ¹³ C and ¹⁵ N resonance assignments for TTR(105–115) formed the basis for the extraction of a set of distance and dihedral angle restraints. A total of 76 self-consistent experimental measurements, including 41 restraints on 19 backbone dihedral angles and 35 ¹³ C– ¹⁵ N distances between 3 and 6 Å were obtained from 2D and 3D NMR spectra recorded on three fibril samples uniformly ¹³ C, ¹⁵ N-labeled in consecutive stretches of four amino acids and used to calculate an ensemble of peptide structures. Our results indicate that TTR(105–115) adopts an extended β-strand conformation in the amyloid fibrils such that both the main- and side-chain torsion angles are close to their optimal values. Moreover, the structure of this peptide in the fibrillar form has a degree of long-range order that is generally associated only with crystalline materials. These findings provide an explanation of the unusual stability and characteristic properties of this form of polypeptide assembly.

Purpose: Modern imaging technologies such as CT, PET, SPECT, and MRI employ contrast agents to visualize the tumor microenvironment, providing information on malignancy and response to treatment. Currently, all clinical imaging agents require chemical labeling, i.e. with iodine (CT), radioisotopes (PET/SPECT), or paramagnetic metals (MRI). The goal was to explore the possibility of using simple D‐glucose as an infusable biodegradable MRI agent for cancer detection.Methods: D‐glucose signals were detected using chemical exchange saturation transfer (glucoCEST) MRI of its hydroxyl groups. Feasibility was established in phantoms as well as in vivo using two human breast cancer cell lines, MDA‐MB‐231 and MCF‐7, implanted orthotopically in nude mice. PET and contrast‐enhanced MRI were also acquired.Results: Both tumor types exhibited significant glucoCEST signal enhancement during systemic sugar infusion (mild hyperglycemia), allowing their noninvasive visualization. GlucoCEST showed differences between types, while PET and CE‐MRI did not. Data are discussed in terms of signal contributions from the increased vascular volume in tumors and especially from the acidic extracellular extravascular space (EES), where glucoCEST signal is expected to be enhanced due to a slow down of hydroxyl proton exchange.Conclusions: This observation opens up the possibility for using simple non‐toxic sugars as contrast agents for cancer detection with MRI by employing hydroxyl protons as a natural label. Magn Reson Med, 2012.

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH‐dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI‐compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly‐L‐lysine (PLL) and a generation‐5 polyamidoamine dendrimer (SPD‐5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH‐calibration curve of the agents consisting of contributions from spontaneous (k₀) acid catalyzed (k_a), and base catalyzed (k_b) exchange rate constants. These constants were k₀ = 68.9 Hz, k_a = 1.21 Hz, k_b = 1.92 × 10⁹ Hz, and k₀ = 106.4 Hz, k_a = 25.8 Hz, k_b = 5.45 × 10⁸ Hz for PLL and SPD‐5, respectively, showing the expected predominance of base‐catalyzed exchange for these amide protons. Magn Reson Med, 2006.