Radiolabeled amino acids (AAs) are an important class of imaging agents for PET and SPECT that target the increased levels of AA transport by many tumor cells. System L AA transport has been a major focus of tracer development, and work in this field has led to several tracers that are effective for imaging brain tumors. Emerging data also support the use of certain radiolabeled AAs for neuroendocrine tumors and prostate cancer. Recently, new 18 F-labeled AAs have been developed that target transporters other than system L, including system A, glutamine, xCT, and cationic AA transporters. This review provides an overview of this class of molecular imaging agents and highlights the current status of oncologic imaging with radiolabeled AAs in terms of tracer considerations and key clinical applications.

Covalently bonded carbon nitride (CN) has stimulated extensive attention as a metal-free semiconductor. However, because of the complexity of polymeric structures, the acquisition of critical roles of each molecular constituent in CN for photocatalysis remains elusive. Herein, we clarify the fundamental active units of CN in photocatalysis by synthesizing CN with more detailed molecular structures. Enabled by microwave synthesis, the as-prepared CN consists of distinguishable melem (M1) and its incomplete condensed form (M2). We disclose rather than the traditional opinion of being involved in the whole photocatalytic processes, M1 and M2 make primary contributions in light absorption and charge separation, respectively. Meanwhile, oxygen molecules are unusually observed to be activated by participating in the photoexcited processes via electronic coupling mainly to M2. As a result, such CN has a higher activity, which was up to 8 times that of traditional bulk CN for photocatalytic oxidation of tetracycline in water.

Due to the toxicity of mercury catalysts, a non-mercury heterogeneous catalyst for acetylene hydrochlorination has been widely investigated. In this review, we introduce the development of Au-based catalysts, Ru-based catalysts, other metal catalysts and a carbon nitride catalyst. The effect of the promoter and the carbon support property on the catalytic performance of the AuCl 3 catalyst is discussed in detail and the potential application of other catalysts is also reviewed on the basis of experimental and theoretical studies. At present, it is predicted that an Au-based catalyst may be the optimal candidate catalyst for industrial application in the production of polyvinyl chloride from calcium carbide, but other catalysts should still be further investigated to improve their catalytic performance and their cost advantages.

Purpose: The P2X7 receptor, an adenosine triphosphate (ATP)-gated purinoreceptor, has emerged as one of the key players in neuroinflammatory processes. Therefore, developing a positron emission tomography (PET) tracer for imaging of P2X7 receptors in vivo presents a promising approach to diagnose, monitor, and study neuroinflammation in a variety of brain disorders. To fulfill the goal of developing a P2X7 PET ligand as a biomarker of neuroinflammation, [ 18 F]JNJ-64413739 has been recently disclosed. Procedures: We evaluated [ 18 F]JNJ-64413739 in a rat model of neuroinflammation induced by an intracerebral injection of lipopolysaccharide (LPS). In vivo brain uptake was determined by PET imaging. Upregulation of neuroinflammatory biomarkers was determined by quantitative polymerase chain reaction (qPCR). Distribution of the tracer in the brain was determined by ex vivo autoradiography (ARG). The specificity of [ 18 F]JNJ-64413739 was confirmed by performing blocking experiments with the P2X7 antagonist JNJ-54175446. Results: Brain regions of rats injected with LPS had a significantly increased uptake (34 % ± 3 % s.e.m., p = 0.036, t test, standardized uptake value measured over the entire scanning period) of [ 18 F]JNJ-64413739 relative to the corresponding brain regions of control animals injected with phosphate-buffered saline (PBS). The uptake in the contralateral regions and cerebellum was not significantly different between the groups of animals. The increase in uptake of [ 18 F]JNJ-64413739 at the LPS-injected site observed by PET imaging was concordant with ex vivo ARG, upregulation of neuroinflammatory biomarkers, and elevated P2X7 expression levels. Conclusions: While further work is needed to study [ 18 F]JNJ-64413739 in other types of neuroinflammation, the current results favorably characterize [ 18 F]JNJ-64413739 as a potential PET tracer of central neuroinflammation.

Sulfinamides were synthesized from sulfonyl chlorides using a procedure involving the in situ reduction of sulfonyl chlorides. The reaction is broad in scope and easy to perform.Sulfinamides, especially chiral sulfinamides, play vital roles in the modern asymmetric chemistry. 1 Furthermore, sulfinamides can also act as N-sulfinyl protecting group in ease of removal under mild conditions. 2 Even though there are various procedures reported for the preparation of sulfinamides from sulfinic acids 3 , sulfinates 4 , sulfinyl chlorides 5 , disulfides 6 , and homolytic substitution at the sulfur atom 7 , these reactions often require two or more synthetic steps. A one-step process would be useful and increase the exploration of sulfinamide chemistry.Sulfinamides are useful compounds and can be transformed to a number of other important functional groups. 8 For example, they can be converted to sulfonimidoyl chlorides, whose chemistry is both interesting and useful. 9 We reported that benzothiazines can be prepared from N-aryl sulfinamides by oxidation with t-butyl hypochlorite and subsequent treatment with an alkene or alkyne in the presence of a Lewis acid. (Scheme 1). 10 The requisite sulfinamide was prepared from a sulfinyl choride in high yield. While sulfinyl chlorides are not exceptionally difficult to make, they are sensitive to hydrolysis and require preparation using noxious reagents such as thionyl chloride. We thought that a procedure to quickly access sulfinamides would be useful in both exploring sulfinamide chemistry and derivatives such as sulfonimidoyl chlorides.A number of years ago Sharpless 11 reported the synthesis of sulfinate esters from sulfonyl chlorides by a one-pot reductive esterification reaction using either phosphites as the reducing agent. Attempts to prepare sulfinamides by the Sharpless group were not successful. We thought however, that the modification of the synthesis of sulfinate esters introduced by Toru 12 , which used triarylphophines as the reductant, would be suitable for the synthesis of such compounds. This letter reports the realization of that idea.We began our studies by simply using Toru's procedure for sulfinate ester formation. 11 The results are summarized in Table 1. When a CH 2 Cl 2 solution of triphenylphosphine was added to the mixture of TsCl, TEA (10 equivalents) and BzNH 2 in CH 2 Cl 2 at 0 °C, only sulfonamide 6 and PPh 3 were detected by the NMR analysis of the crude mixture (entry 1). However, a small change in the addition sequence offered an encouraging result. When PPh 3 and benzylamine in CH 2 Cl 2 were added to a mixture of triethylamine and tosyl chloride, the desired HarmataM@Missouri.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript sulfinamide was isolated in 62% yield, (entry 2). Only a 14% yield of sulfinamide, accompanied by 40% sulfonamide, was isolated when the reaction was performed by the addition of PPh 3 to TsCl in CH 2 Cl 2 over 1 hour followed by addition of a mixture of BzNH 2 and T...

(18)F-labeled amino acids are an important class of imaging agents for positron emission tomography (PET) that target the increased rates of amino acid transport by many tumor cells. This class of tracers is structurally diverse, and the biological and imaging properties of a given (18)F-labeled amino acid depends largely upon its mechanism of transport. The system L amino acid transport system has been a major focus of tracer development in this field, but more recently (18)F-labeled amino acids have been developed for other transporters including system A, glutamine, glutamate and cationic amino acid transport systems. Radiolabeled amino acids are best established for brain tumor imaging, but there are emerging applications in other types of cancer such as neuroendocrine tumors and prostate cancer. This review provides an overview of (18)F-labeled amino acids for oncologic imaging in terms of design considerations, radiosynthetic methods, and key clinical applications.

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The P2X7 receptor is an adenosine triphosphate-gated ion channel, which is abundantly expressed in glial cells within the central nervous system and in the periphery. P2X7 receptor activation leads to the release of the proinflammatory cytokine IL-1β in the brain, and antagonism of the P2X7 receptor is a novel therapeutic strategy to dampen adenosine triphosphate-dependent IL-1β signaling. PET ligands for the P2X7 receptor will not only be valuable to assess central target engagement of drug candidates but also hold promise as surrogate markers of central neuroinflammation. Herein we describe the in vitro and in vivo evaluation of 18 F-JNJ-64413739, an 18 F-labeled PET ligand for imaging the P2X7 receptor in the brain. Methods: P2X7 receptor affinity and specificity, pharmacokinetics, metabolic stability, blood-brain barrier permeability, and off-target binding of JNJ-64413739 were evaluated in a series of in vitro, ex vivo, and in vivo assays. 18 F-JNJ-64413739 was radiolabeled via a one-step nucleophilic aromatic substitution. The tracer was also studied in rhesus macaques, and PET images were analyzed with an arterial plasma input function-based Logan graphical analysis. Results: The potency (half-maximal inhibitory concentration) of the P2X7 receptor antagonist JNJ-64413739 is 1.0 ± 0.2 nM and 2.0 ± 0.6 nM at the recombinant human and rat P2X7 receptor, respectively, and the binding affinity is 2.7 nM (rat cortex binding assay) and 15.9 nM (human P2X7 receptor). In nonhuman primate PET imaging studies, dose-dependent receptor occupancy of JNJ-54175446 was observed in 2 rhesus monkeys. At a 0.1 mg/kg dose (intravenous) of JNJ-54175446, the receptor occupancy was calculated to be 17% by Logan graphical analysis, whereas a dose of 2.5 mg/kg yielded a receptor occupancy of 60%. Conclusion: The preclinical evaluation of 18 F-JNJ-64413739 demonstrates that the tracer engages the P2X7 receptor. Reproducible and dose-dependent receptor occupancy studies with the P2X7 receptor antagonist JNJ-54175446 were obtained in rhesus monkeys. This novel PET tracer exhibits in vitro and in vivo characteristics suitable for imaging the P2X7 receptor in the brain and warrants further studies in humans.