Spectroscopic and electrochemical studies of new copper(II) and nickel(II) N2S2 tetradentate complexes of potential interest to nuclear medicine

The coupling of radionuclides such as copper (67Cu and 64Cu) to antibodies by bifunctional chelating agents (or BCA) requires extremely high stability to avoid in vivo release of metal. Six copper(II) and five nickel(II) complexes with N2S2 tetradentate ligands were synthesised for potential medical applications, and stability studies were conducted. I.r and u.v.-vis. spectra provided structural data on the geometry of the complexes. The redox potentials obtained from cyclic voltammetry allowed us to estimate the stability constants of each complex and then select the more suitable ligand for future applications in radioimmunotherapy.     

New Fully Automated Preparation of High Apparent Molar Activity 68Ga-FAPI-46 on a Trasis AiO Platform

A large number of applications for fibroblast activation protein inhibitors (FAPI)-based PET agents have been evaluated in conditions ranging from cancer to non-malignant diseases such as myocardial infarction. In particular, ⁶⁸Ga-FAPI-46 was reported to have a high specificity and affinity for FAP-expressing cells, a fast and high accumulation in tumor lesions/injuries together with a fast body clearance when investigated in vivo. Due to the increasing interest in the use of the agent both preclinically and clinically, we developed an automated synthesis for the production of ⁶⁸Ga-FAPI-46 on a Trasis AiO platform. The new synthetic procedure, which included the processing of the generator eluate using a strong cation exchange resin and a final purification step through an HLB followed by a QMA cartridge, yielded ⁶⁸Ga-FAPI-46 with high radiochemical purity (>98%) and apparent molar activity (271.1 ± 105.6 MBq/nmol). Additionally, the in vitro and in vivo properties of the product were assessed on glioblastoma cells and mouse model. Although developed for the preparation of ⁶⁸Ga-FAPI-46 for preclinical use, our method can be adapted for clinical production as a reliable alternative to the manual (i.e., cold kit) or modular systems preparations already described in the literature.     

On Ramsey‐type positional games

Let K denote the graph obtained from the complete graph K_s+t by deleting the edges of some K_t‐subgraph. We prove that for each fixed s and sufficiently large t, every graph with chromatic number s+t has a K minor. © 2010 Wiley Periodicals, Inc. J Graph Theory 65: 343–350, 2010     

Conformal autosimilarity

We prove that the conformally autosimilar closed subsets of the Euclidean sphere are exactly the limit sets of convex cocompact Kleinian groups. We also prove other similar results.     

Systematic ratio normalization of gas chromatography signals for biological sample discrimination and biomarker discovery

The present paper introduces a new gas chromatography data processing procedure dubbed systematic ratio normalization (SRN) enabling to improve both sample set discrimination and biomarker identification. SRN consists in (1) calculating, for each sample, all the log-ratios between abundances of chromatography-analyzed compounds, then (2) selecting the log-ratio(s) that best maximize the discrimination between sample-sets. The relevance of SRN was evaluated on two data sets acquired through gas chromatography–mass spectrometry as part of separate studies designed (i) to discriminate source-origins between vegetable oils analyzed via an analytical system exposed to instrument drift (data set 1) and (ii) to discriminate animal feed between meat samples aged for different durations (data set 2). Applying SRN to raw data made it possible to obtain robust discrimination models for the two data sets by enhancing the contribution to the data variance of the factor-of-interest while stabilizing the contribution of the disturbance factor. The most discriminant log-ratios were shown to employ the most relevant biomarkers presenting relative independence of the factor-of-interest as well as co-behavior of the disturbance effects potentially biasing the discrimination, such as instrument drift or sample biochemical changes. SRN can be run a posteriori on any data set, and might be generalizable to most of separating methods.     

Synthesis of New 9‐Methylene Analogs of Retinoids

We report herein a series of syntheses that provides diverse structural modifications of the side‐chain of retinoids to obtain new compounds with potential use in anticancer therapy. Starting from a β‐methylenealdehyde synthon, we have synthesized a series of new 9‐methylene‐13‐desmethyl‐14‐methyl analogs and a series of 9‐methylene‐11‐desmethyl trienic homologs. For the first series, the condensation of the C‐15 β‐methylenealdehyde with the anion of ethyl 4‐(diethoxyphosphoryl)‐2E‐methylbut‐2‐enoate led to the 7E,11E,13E‐ester. This gave the desired aldehyde by a reduction into the corresponding alcohol (DIBAL‐H) and subsequent oxidation by MnO₂. For the second series, the reaction of the C‐15 β‐methylenealdehyde with the anions of ethyl diethoxyphosphorylacetate, diethyl cyanomethylphosphonate, or diethyl 2‐oxopropylphosphonate led to the C‐17 ester, the C‐17 nitrile, and the C‐18 ketone, respectively.     

First dinuclear Re/Tc complex as a potential bimodal Optical/SPECT molecular imaging agent

In this communication, a novel synthetic pathway has been applied to prepare a dual imaging agent in a single molecule. The dinuclear Re(I)/Tc(I) complex 6, namely [Re(CO)(3)(bipy){(4-PyrIDA)Tc(CO)(3)}], is the first example of a Re/Tc-based heterometallic assembly which could act as a potential bimodal Optical/SPECT probe. Interestingly, the Re(I) complex intermediate 4 exhibits significant photophysical properties for biological applications.