Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging

PURPOSE: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. METHODS AND MATERIALS: The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. RESULTS: Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. CONCLUSION: NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.     

A hetero-stranded double helix composed of m-diethynylbenzene-based complementary molecular strands stabilized by amidinium-carboxylate salt bridges

A hetero-stranded double helix with a controlled helix sense was designed and synthesized from an optically active dimeric amidine and its complementary achiral dicarboxylic acid strand with conjugated m-diethynylbenzene backbones, being stabilized by the salt bridges.     

Trace element distributions in man-made fibers

A preliminary study to evaluate the use of neutron activation analysis for the characterization of six groups of man-made fibers for forensic purposes has been made. A total of 81 samples of acetate, acrylic, modacrylic, nylon, polyester and rayon were analyzed. Small samples, approximately the size typically found during a crime scene search, were analyzed using a Ge(Li) detector system following a 20 min irradiation at a flux of 5·10¹³ n·cm⁻²·sec⁻¹. The following elements were determined quantitatively in one or more of the samples: Ti, Sr, Au, Zn, Sb, Br. Mn, Mg, Cu, In, Co, Cu, V, K, Al, Cl, Na, Ca, and S. Significant qualitative and quantitative differences were found both between and within the six groups. However, within certain groups some fibers from different manufacturers showed marked similarities in qualitative and quantitative composition.     

Studies on phosphonic acid antibiotics. II. Synthesis of 3-(n-acetyl-n-hydroxyamino)-2(r)-hydroxypropylphosphonic acid (FR-33289) and 3-(n-formyl-n-hydroxyamino)-1-trans-propenylphosphonic acid (FR-32863)

The syntheses of FR-33289 ($\text{3}$), originally isolated from a microorganism, and FR-32863 ($\text{6}$), first designed on the basis of a biogenetic consideration and recently found to be also present in nature, are described.     

Separation of N2@C60 and N@C60

We describe the HPLC separation and identification of N@C60 and N2@C60. These species were observed after eleven sequential HPLC separations. Their retention times are in the same range as those of the other noninteractive endohedral species of C60, such as noble gas endohedral C60. The separation factors of these endohedrals were evaluated by using a mixture of hexane/toluene as eluent. We note that this is the first evidence for the N2@C60 molecule existing in the form of endohedral C60 complex.     

Synthesis of the C42-C52 part of ciguatoxin CTX3C

The C42-C52 part of ciguatoxin CTX3C (1) was synthesized from tri-O-acetyl d-glucal. The synthetic segment had a tetrahydropyran ring corresponding to the ‘C49-reduced’ L-ring of 1, designed to avoid side reactions due to acid-labile C49 acetal carbon during acidic reductive conditions planned in further synthesis toward 1. The vicinal dimethyl part at C47-C48 was constructed by a stepwise conjugate addition/methylation procedure. The C50-C52 unit was installed by Grignard addition of the C₃ unit followed by spirocyclization and reductive cleavage of the spirocyclic acetal. Stereoselective assembly of the C42-C44 part was achieved by Brown’s asymmetric crotylboration.     

Preparation and interfacial properties of a novel biodegradable polymer surfactant: poly(ethylene oxide monooleate-block-DL-lactide)

In this paper, we report a novel synthesis of poly(ethylene oxide monooleate-block-DL-lactide) (MOPEO-PLA) in the presence of stannous 2-ethylhexanoate catalyst. By utilizing the surfactant property and the reactive double bond of the amphiphilic MOPEO-PLA, various characteristics of PLA microspheres, such as surface and internal structure, surface morphology, release property, and so on, may potentially be controlled. MOPEO-PLA was found to be hydrophobic enough to prevent loss by dissolution into aqueous solution, which is often a problem for MOPEO. Furthermore, the interfacial tension measurements of a MOPEO-PLA/toluene/water system revealed that MOPEO-PLA had a good surface activity almost equal to that of MOPEO. The MOPEO-PLA/PLA blend films were prepared by solvent casting on a water layer. Contact-angle measurements of MOPEO-PLA/PLA blend films confirmed that the hydrophilic PEO segments were selectivity accumulated at the oil/water interface. Moreover, the surface free energy on the 'water side' of the MOPEO-PLA/PLA blend films was increased because of the increase in polar components as a result of the ether bonds of the PEO segments. Schematic illustration of the adsorption property of a) MOPEO-PLA with a high-molecular-weight PLA segment and b) MOPEO-PLA with a low-molecular-weight PLA segment at an ethyl acetate/water interface.     

Photoactivation of a substrate for cell adhesion under standard fluorescence microscopes

Cell-culturing substrates where cell adhesion can be switched on by external stimuli during cell cultivation are useful scaffolds for tissue engineering, cell-based drug screening, and fundamental cellular studies. Here, we show a new strategy for photoactivation of a substrate for cell adhesion under standard fluorescence microscopes. A glass substrate chemically modified with an alkylsiloxane having a photocleavable 2-nitrobenzyl group was coated with bovine serum albumin to prevent cell adhesion. Upon irradiation under a fluorescence microscope, the protein was replaced with fibronectin, which made the irradiated region cell-adhesive. Subsequent seeding of HEK293 or COS7 cells produced patterns corresponding to the irradiated patterns. We succeeded for the first time in positioning single cells in proximity to cultivating single cells. The present method provides a general strategy for positioning single cells of same or different types at any locations on the substrate and will be useful for studying cell-cell interactions.     

Property control of new forms of carbon materials by fluorination

Multiwall carbon nanotubes (MWNTs) based on the template carbonization technique were fluorinated in a temperature range 323-473 K by elemental fluorine. The fluorination of the carbon nanotubes results in functionalization and modification of pristine nanotubes with respect to adsorption and electrochemical properties. Selective fluorination of the inner surface of the carbon nanotubes, brings about a decrease in the surface free energy of the inner surface of the tubes and an increase in colombic efficiency of Li/nanotubes rechargeable cells in an aprotic medium. Electrochemical fluoride-ion doping of fullerene C₆₀ thin films (250-450 nm) was carried out in a fluoride-ion conductive solution, MeCN solution of 1 M Et₄NF·4HF. Galvanostatic oxidation yielded C₆₀F_ca.1-3 where fluorine exists as a semi-ionic species in the cavity surrounded by C₆₀ molecules without forming covalent CF bonds