Control of the Platinum(II) ligating properties of rigid 1,2-diamines: the case of trans-2,3-diaminonorbornane.

Guided by a simple predictive model, a norbornane-based trans-1,2-diamine was identified as a potential bridging ligand for di-nuclear platinum complex formation; efficient synthesis and product characterization confirmed this hypothesis

Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18

International audienceWith the aim to develop a specific radioligand for imaging the cyclic nucleotide phosphodiesterase 5 (PDE5) in brain by positron emission tomography (PET), seven new fluorinated inhibitors (3-9) were synthesized on the basis of a quinoline core. The inhibitory activity for PDE5 together with a panel of other PDEs was determined in vitro and two derivatives were selected for IC50 value determination. The most promising compound 7 (IC50 = 5.92 nM for PDE5A), containing a 3-fluoroazetidine moiety, was further radiolabeled by aliphatic nucleophilic substitution of two different leaving groups (nosylate and tosylate) using [18F]fluoride. The use of the nosylate precursor and tetra-n-butyl ammonium [18F]fluoride ([18F]TBAF) in 3-methyl-3-pentanol combined with the addition of a small amount of water proved to be the best radiolabeling conditions achieving a RCY of 4.9 ± 1.5% in an automated procedure. Preliminary biological investigations in vitro and in vivo were performed to characterize this new PDE5 radioligand. Metabolism studies of [18F]7 in mice revealed a fast metabolic degradation with the formation of radiometabolites which have been detected in the brain

Use of 3-[18F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

3-[18F]Fluoropropanesulfonyl chloride, a recently proposed prosthetic agent for fluorine-18 labelling, was prepared in a two-step radiosynthesis via 3-[18F]fluoropropyl thiocyanate as an intermediate. Two benzenesulfonate-based radiolabelling precursors were prepared by various routes. Comparing the reactivities of 3-thiocyanatopropyl nosylate and the corresponding tosylate towards [18F]fluoride the former proved to be superior accounting for labelling yields of up to 85%. Conditions for a reliable transformation of 3-[18F]fluoropropyl thiocyanate to the corresponding sulfonyl chloride with the potential for automation have been identified. The reaction of 3-[18F]fluoropropanesulfonyl chloride with eight different aliphatic and aromatic amines was investigated and the identity of the resulting 18F-labelled sulfonamides was confirmed chromatographically by comparison with their nonradioactive counterparts. Even for weakly nucleophilic amines such as 4-nitroaniline the desired radiolabelled sulfonamides were accessible in satisfactory yields owing to systematic variation of the reaction conditions. With respect to the application of the 18F-fluoropropansulfonyl group to the labelling of compounds relevant as imaging agents for positron emission tomography (PET), the stability of N-(4-fluorophenyl)-3-fluoropropanesulfonamide against degradation catalysed by carboxylesterase was investigated and compared to that of the analogous fluoroacetamide

Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoroalkyl homologs

International audienc

The Use of [ 125 I] Scintigraphic In Vivo Imaging in Melanoma-Bearing Mice for a Rapid Prescreening of Vectors to Melanoma Tissue

International audienc

Radiosynthesis and Radiotracer Properties of a 7-(2-[18F]Fluoroethoxy)-6-methoxypyrrolidinylquinazoline for Imaging of Phosphodiesterase 10A with PET

International audienc

Interest and Limits of [18F]ML-10 PET Imaging for Early Detection of Response to Conventional Chemotherapy

International audienceOne of the current challenges in oncology is to develop imaging tools to early detect the response to conventional chemotherapy and adjust treatment strategies when necessary. Several studies evaluating PET imaging with 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) as a predictive tool of therapeutic response highlighted its insufficient specificity and sensitivity. The [ 18 F]FDG uptake reflects only tumor metabolic activity and not treatment-induced cell death, which seems to be relevant for therapeutic evaluation. Therefore, to evaluate this parameter in vivo , several cell death radiotracers have been developed in the last years. However, few of them have reached the clinical trials. This systematic review focuses on the use of [ 18 F]ML-10 (2-(5-[ 18 F]fluoropentyl)-2-methylmalonic acid) as radiotracer of apoptosis and especially as a measure of tumor response to treatment. A comprehensive literature review concerning the preclinical and clinical investigations conducted with [ 18 F]ML-10 was performed. The abilities and applications of this radiotracer as well as its clinical relevance and limitations were discussed. Most studies highlighted a good ability of the radiotracer to target apoptotic cells. However, the increase in apoptosis during treatment did not correlate with the radiotracer tumoral uptake, even using more advanced image analysis (voxel-based analysis). [ 18 F]ML-10 PET imaging does not meet current clinical expectations for early detection of the therapeutic response to conventional chemotherapy. This review has pointed out the challenges of applying various apoptosis imaging strategies in clinical trials, the current methodologies available for image analysis and the future of molecular imaging to assess this therapeutic response

A 18F-Labeled Fluorobutyl-Substituted Spirocyclic Piperidine Derivative as a Selective Radioligand for PET Imaging of Sigma1 Receptors

International audienc

Synthesis, Radiofluorination, and in Vivo Evaluation of Novel Fluorinated and Iodinated Radiotracers for PET Imaging and Targeted Radionuclide Therapy of Melanoma

International audienc