PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin α_vβ₃ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin α_vβ₃ tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (¹⁸F, ⁶⁴Cu, and ⁶⁸Ga), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included.     

Water suppression without signal loss in HR-MAS 1H NMR of cells and tissues

In cell and tissue samples, water is normally three orders of magnitude more abundant than other metabolites. Thus, water suppression is required in the acquisition of NMR spectra to overcome the dynamic range problem and to recover metabolites that overlap with the broad baseline of the strong water resonance. However, the heterogeneous cellular environment often complicates water suppression and the strong coupling of water to membrane lipids interferes with the NMR detection of membrane associated lipid components. The widely used water suppression techniques including presaturation and double pulsed field gradient selective echo result in more than a 70% reduction in membrane associated lipid components in proton spectra of cells and tissues compared to proton spectra acquired in the absence of water suppression. A water suppression technique based on the combination of selective excitation pulses and pulsed field gradients is proposed to use in the acquisition of high resolution MAS NMR spectra of tissue specimens and cell samples. This pulse sequence methodology enables efficient water suppression for intact cells and tissue samples and eliminates signal loss from cellular metabolites.     

EQUITY ISSUES AFFECTING MATHEMATICS LEARNING USING ICT

Our concern is the inequities that arise from differential access and use of educational technology in mathematics for groups characterised by gender, ethnicity, income level and ability. As access to information and communications technology (ICT) increases both in homes and schools, our paper asks whether previous inequities are being ironed out or exacerbated. Equity is considered from the three perspectives proposed by Fennema (1990), namely in terms of: (a) opportunities to learn (physical access); (b) educational treatment (how technology is used, by whom), and the social and psychological factors influencing its use; (c) educational outcomes (impacts on achievement, attitudes and motivation). Suggested policies and pedagogies for removing the boundaries between technology ‘haves’ and ‘have-nots’ are presented.     

The magnetic structure of HoCo2Si2

We have carried out neutron diffraction on a HoCo₂Si₂ powder sample at 4.2 K. The magnetic structure of this compound is collinear antiferromagnetic with the holmium magnetic moments parallel to the c-axis of the crystal. The magnetic moment value of holmium is 9.85 μ_B. The magnetic space group is I4/mm'm' (Sh⁴¹⁰₁₂₈) k = 000 The ordering temperature is t_n = 12(1) K.     

On the magnetic structure and magnetic phase transitions of Tb5Ge4. A Neutron diffraction study

Tb₅Ge₄ crystallizes in the orthorhombic space group Pnma, and orders antiferromagnetically below T_N = 91K. Neutron diffraction powder data at 4.2K reveal a ten-sublattice canted antiferromagnetic arrangment. The structure, which is described by the magnetic space group Pnm'a (Γ_8u) with propagation vector k = 0, has three-dimensional components for the atoms in the 8(d) positions, and is almost colinear for the atoms in the 4(c) positions. The magnetic interaction in the layers formed by the Tb atoms in the (010) plane is mainly ferromagnetic, in agreement with the high paramagnetic Curie temperature of 85K. The structure is antiferromagnetically compensated through an antisymmetry center. The main axis of antiferromagnetism is parallel to z. Magnetic phase transitions have been observed by applying a magnetic field in the (010) plane. The structure is stabilized through exchange interactions via conduction electrons. Because of the low symmetry, the Hamiltonian may contain anisotropic terms that result in a canted arrangement.     

Reactions of O 3PJ atoms with halogens: The rate constants for the elementary reactions O + BrCl,O + Br2, and O + Cl2

Direct determinations of the rate constants (cm³/molec · sec) k₁, k₂, and k₃ from 298 to 299°K are reported, using atomic resonance fluorescence in discharge flow systems:

1 One standard deviation.

The rate constant k₁, which has not been determined previously, was found to possess an insignificant temperature coefficient (E_A = (0 ± 700) J/mole) in the range of 299 to 619°K. The present result for k₂ agrees well with reinterpreted values from the one previous determination. Measurements of O atom consumption rates and Br atom production rates in the O + Br₂ reaction are interpreted to give an estimate of the rate constant k₄, which has not been reported previously, at 298°K: k₃ has been measured at three temperatures between 299 and 602°K. The present and previous results for k₃ were combined to give the following rate expression:      

Crystal structures of ester derivatives of 2,6-bis(1-pyrrolidinylmethyl)-4-benzamidophenol antiarrhythmic agents

The N atoms in both of the pyrrolidine rings in the title compounds are protonated which prevents the formation of an intramolecular hydrogen bond between the phenol OH group and the ring N atom. This hydrogen bond is thought to be important for maintaining the active shape of these drugs. The positions of the pyrrolidine rings are determined by a chain of hydrogen bonds which link the N⁺–H through the Cl^– back to portions of the same molecule. In both molecules, the carbonyl bond of the ester substituent is aligned parallel to the carbonyl bond of the central amide. The benzanilide fragment is flattened relative to the common conformation found in tabulated structures. Extensive hydrogen bonding is observed due to the presence of solvent and chloride ions. Compound1, 2,6-bis(1-pyrrolidinylmethyl)-4-(4-carboethoxybenzamido)phenol, crystallizes as the dihydrochloride methanol hydrate in the monoclinic space group C2/c with 8 molecules per unit cell and cell constants:a=20.3013,b=11.296(2),c=24.901(5)Å, =93.19(1)°, 4945 unique reflections, 2946 observed,R=0.071. Compound2, 2,6-bis[1-pyrrolidinylmethyl-4-[4-(2-carboethoxyethyl)benzamido]phenol, crystallizes as the dihydrochloride salt in the monoclinic space group P2₁/c with 4 molecules per unit cell anda=12.903(3),b=16.430(4),c=13.731(2)Å, =103.64(2)°, 5712 unique reflections, 2449 observed,R=0.057.