Vacuum ultraviolet photon-mediated production of [F-18]F-2

The chemistry of F-2 and its derivatives are amenable to facile aliphatic or aromatic substitution, as well as electrophilic addition. The main limitation in the use of [F-18]F-2 for radiopharmaceutical synthesis is the low specific activity achieved by the traditional methods of production. The highest specific activities, 55GBq/mol, for [F-18]F-2 have been achieved so far by using electrical discharge in the post-target production of [F-18]F-2 gas from [F-18]CH3F. We demonstrate that [F-18]F-2 is produced by illuminating a gas mixture of neon/F-2/[F-18]CH3F with vacuum ultraviolet photons generated by an excimer laser. We tested several illumination chambers and production conditions. The effects of the initial amount of [F-18]F-, amount of carrier F-2, and number of 193-nm laser pulses at constant power were evaluated regarding radiochemical yield and specific activity. The specific activity attained for [F-18]F-2-derived [F-18]NFSi was 10.3 +/- 0.9GBq/mol, and the average radiochemical yield over a wide range of conditions was 6.7% from [F-18]F-. The production can be improved by optimization of the synthesis device and procedures. The use of a commercially available excimer laser and the simplicity of the process can make this method relatively easy for adaptation in radiochemistry laboratories

Radiosynthesis and Preclinical Evaluation of an α2A-Adrenoceptor Tracer Candidate, 6-[18F]Fluoro-marsanidine

Purpose: The α2-adrenoceptors mediate many effects of norepinephrine and epinephrine, and participate in the regulation of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. Of the three receptor subtypes, only α2A and α2C are found in the brain in significant amounts. Subtype-selective positron emission tomography (PET) imaging of α2-adrenoceptors has been limited to the α2C subtype. Here, we report the synthesis of 6-[18F]fluoro-marsanidine, a subtype-selective PET tracer candidate for α2A-adrenoceptors, and its preclinical evaluation in rats and mice.Procedures: 6-[18F]Fluoro-marsanidine was synthesized using electrophilic F-18 fluorination with [18F]Selectfluor bis(triflate). The tracer was evaluated in Sprague Dawley rats and in α2A-knockout (KO) and wild-type (WT) mice for subtype selectivity. In vivo PET imaging and ex vivo brain autoradiography were performed to determine the tracer distribution in the brain. The specificity of the tracer for the target was determined by pretreatment with the subtype-non-selective α2-agonist medetomidine. The peripheral biodistribution and extent of metabolism of 6-[18F]fluoro-marsanidine were also analyzed.Results: 6-[18F]Fluoro-marsanidine was synthesized with [18F]Selectfluor bis(triflate) in a radiochemical yield of 6.4 ± 1.7 %. The molar activity was 3.1 to 26.6 GBq/μmol, and the radiochemical purity was > 99 %. In vivo studies in mice revealed lower uptake in the brains of α2A-KO mice compared to WT mice. The results for selectivity were confirmed by ex vivo brain autoradiography. Blocking studies revealed reduced uptake in α2A-adrenoceptor-rich brain regions in pretreated animals, demonstrating the specificity of the tracer. Metabolite analyses revealed very rapid metabolism of 6-[18F]fluoro-marsanidine with blood-brain barrier-permeable metabolites in both rats and mice.Conclusion: 6-[18F]Fluoro-marsanidine was synthesized and evaluated as a PET tracer candidate for brain α2A-adrenoceptors. However, rapid metabolism, extensive presence of labeled metabolites in the brain, and high non-specific uptake in mouse and rat brain make 6-[18F]fluoro-marsanidine unsuitable for α2A-adrenoceptor targeting in rodents in vivo.</p

Comparison of high and low molar activity TSPO tracer [18F]F-DPA in a mouse model of Alzheimer’s disease

[18F]F-DPA, a novel translocator protein 18 kDa (TSPO)-specific radioligand for imaging neuroinflammation, has to date been synthesized with low to moderate molar activities (Am’s). In certain cases, low Am can skew the estimation of specific binding. The high proportion of the non-radioactive component can reduce the apparent-specific binding by competitively binding to receptors. We developed a nucleophilic synthesis of [18F]F-DPA resulting in high Am (990 ± 150 GBq/µmol) and performed in vivo comparison with low Am (9.0 ± 2.9 GBq/µmol) [18F]F-DPA in the same APP/PS1-21 and wild-type mice (injected masses: 0.34 ± 0.13 µg/kg and 38 ± 15 µg/kg, respectively). The high level of microgliosis in the APP/PS1-21 mouse model enables good differentiation between diseased and healthy animals and serves better to distinguish the effect of differing Am on specific binding. The differing injected masses affect the washout profile and shape of the time–activity curves. Ratios of standardized uptake values obtained with high and low Am [18F]F-DPA demonstrate that there is a 1.5-fold higher uptake of radioactivity in the brains of APP/PS1-21 animals when imaging is carried out with high Am [18F]F-DPA. The differences between APP/PS1-21 and wild-type animals showed higher significance when high Am was used.</p

Diastereoselective synthesis of tetraalkyl (R,R)-1,2-cyclohexylene-diamino-di-phosphonates bearing thiophene, furan and pyrrole moieties. Computational and experimental study on their formation

cited By 1International audienceDiastereoselective additions of dialkyl phosphites to three diimines bearing DACH moiety and thiophene, furan or pyrrole rings were studied in the aspect of their stereochemistry, structure of predominant products and mechanism. For these reasons, analysis of reaction mixture, X-ray studies of products, UV-photoelectron spectroscopy and ionization energies of the starting imines were performed experimentally while reaction profiles were calculated at the CAM-B3LYP/6-311G(d,p) level of theory. The calculated energy barriers corresponding to the gas phase are significantly low and seem to explain why the products are formed relatively easily

Ultrafast click chemistry with fluorosydnones.

We report the synthesis and reactivity of 4-fluorosydnones, a unique class of mesoionic dipoles displaying exquisite reactivity towards both copper-catalyzed and strain-promoted cycloaddition reactions with alkynes. Synthetic access to these new mesoionic compounds was granted by electrophilic fluorination of σ-sydnone Pd(II) precursors in the presence of Selectfluor. Their reactions with terminal and cyclic alkynes were found to proceed very rapidly and selectively, affording 5-fluoro-1,4-pyrazoles with bimolecular rate constants up to 10(4)  m(-1)  s(-1) , surpassing those documented in the literature with cycloalkynes. Kinetic studies were carried out to unravel the mechanism of the reaction, and the value of 4-fluorosydnones was further highlighted by successful radiolabeling with [(18) F]Selectfluor