The Use of Phage-Displayed Peptide Libraries to Develop Tumor-Targeting Drugs

Monoclonal antibodies have been successfully utilized as cancer-targeting therapeutics and diagnostics, but the efficacies of these treatments are limited in part by the size of the molecules and non-specific uptake by the reticuloendothelial system. Peptides are much smaller molecules that can specifically target cancer cells and as such may alleviate complications with antibody therapy. Although many endogenous and exogenous peptides have been developed into clinical therapeutics, only a subset of these consists of cancer-targeting peptides. Combinatorial biological libraries such as bacteriophage-displayed peptide libraries are a resource of potential ligands for various cancer-related molecular targets. Target-binding peptides can be affinity selected from complex mixtures of billions of displayed peptides on phage and further enriched through the biopanning process. Various cancer-specific ligands have been isolated by in vitro, in vivo, and ex vivo screening methods. As several peptides derived from phage-displayed peptide library screenings have been developed into therapeutics in current clinical trials, which validates peptide-targeting potential, the use of phage display to identify cancer-targeting therapeutics should be further exploited

MODELE STRUCTURAL DES ALLIAGES AMORPHES Ni66B34 ET Ni71B29

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Electron transport and kinetics of transformations in the amorphous alloy Ni66B34

The amorphous alloy Ni66B34 prepared by chemical methods at 20 °C appears to be formed of a large number of clusters of about 8 Å, surrounded by a disordered matrix, the former giving to the latter local order similar to that of the boride Ni3B. The kinetics of transformations which accompany all thermal treatments of the material at a temperature above 20 °C are deduced from study of the resulting isotherm of decreasing electrical resistivity. Two regions of linear increase in apparent activation energy Ea are defined versus annealing temperature : the first in the temperature domain where the alloy maintains its amorphous character; the second beyond 350 °C, corresponding to precipitation of the crystallized phases.L'alliage amorphe Ni66B34 préparé par voie chimique à 20° C apparait comme constitué d'un grand nombre d'agrégats de 8 Å environ, noyés dans une matrice désordonnée, et qui lui confère un ordre local voisin de celui du borure Ni3B. La cinétique des transformations qui accompagnent tout traitement thermique du matériau à une température supérieure à 20 °C est déduite de l'étude des isothermes de décroissance de la résistivité électrique qui en résulte. Deux domaines d'accroissement linéaire de l'énergie d'activation apparente Ea sont définis en fonction de la température de recuit : le premier dans le domaine de températures où l'alliage conserve son caractère amorphe, le deuxième au-delà de 350 °C qui correspond à la précipitation des phases cristallines

OBSERVATIONS OF AMORPHOUS ALLOY CHARACTERISTICS USING THE SCANNING MICROSCOPE

Les alliages amorphes obtenus par méthode électrolytique sont déposés sur une feuille de cuivre à la température ambiante. Comme les verres d'oxyde, ces verres métalliques sont des matériaux désordonnés à l'échelle moléculaire. Mais les observations au microscope à balayage révèlent un même comportement à l'examen des surfaces de fracture.Amorphous alloys obtained by electrolytical methods are deposited on a copper leaf at ambient temperature. In commun with the oxide glasses, these metallic glasses are disordonned materials on the molecular scale. But observations with a scanning microscope reveal the same behaviour if we examine the fracture surfaces

Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

PBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[18F]F-Kryptofix 222 and 6.8-7.6 μ mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [18F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/μ mol (2-4 Ci/μ mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [18F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). © 2008 John Wiley & Sons, Ltd

In vivo imaging of brain lesions with [11C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors

The peripheral benzodiazepine receptor (PBR) is expressed by microglial cells in many neuropathologies involving neuroinflammation. PK11195, the reference compound for PBR, is used for positron emission tomography (PET) imaging but has a limited capacity to quantify PBR expression. Here we describe the new PBR ligand CLINME as an alternative to PK11195. In vitro and in vivo imaging properties of [11C]CLINME were studied in a rat model of local acute neuroinflammation, and compared with the reference compound [11C]PK11195, using autoradiography and PET imaging. Immunohistochemistry study was performed to validate the imaging data. [11C]CLINME exhibited a higher contrast between the PBR-expressing lesion site and the intact side of the same rat brain than [11C]PK11195 (2.14 ± 0.09 vs. 1.62 ± 0.05 fold increase, respectively). The difference was due to a lower uptake for [11C]CLINME than for [11C]PK11195 in the non-inflammatory part of the brain in which PBR was not expressed, while uptake levels in the lesion were similar for both tracers. Tracer localization correlated well with that of activated microglial cells, demonstrated by immunohistochemistry and PBR expression detected by autoradiography. Modeling using the simplified tissue reference model showed that R1 was similar for both ligands (R1 ∼ 1), with [11C]CLINME exhibiting a higher binding potential than [11C]PK11195 (1.07 ± 0.30 vs. 0.66 ± 0.15). The results show that [11C]CLINME performs better than [11C]PK11195 in this model. Further studies of this new compound should be carried out to better define its capacity to overcome the limitations of [11C]PK11195 for PBR PET imaging. © 2007 Wiley-Liss, Inc