Radiosynthesis, in vitro and preliminary in vivo evaluation of the novel glutamine derived PET tracers [18F]fluorophenylglutamine and [18F]fluorobiphenylglutamine

INTRODUCTION: Glucose has been deemed the driving force of tumor growth for decades. However, research has shown that several tumors metabolically shift towards glutaminolysis. The development of radiolabeled glutamine derivatives could be a useful molecular imaging tool for visualizing these tumors. We elaborated on the glutamine-derived PET tracers by developing two novel probes, namely [(18)F]fluorophenylglutamine and [(18)F]fluorobiphenylglutamine MATERIALS AND METHODS: Both tracers were labelled with fluorine-18 using our recently reported ruthenium-based direct aromatic fluorination method. Their affinity was evaluated with a [(3)H]glutamine inhibition experiment in a human PC-3 and a rat F98 cell line. The imaging potential of [(18)F]fluorophenylglutamine and [(18)F]fluorobiphenylglutamine was tested using a mouse PC-3 and a rat F98 tumor model. RESULTS: The radiosynthesis of both tracers was successful with overall non-decay corrected yields of 18.46 ± 4.18 % (n=10) ([(18)F]fluorophenylglutamine) and 8.05 ± 3.25 % (n=5) ([(18)F]fluorobiphenylglutamine). In vitro inhibition experiments showed a moderate and low affinity of fluorophenylglutamine and fluorobiphenylglutamine, respectively, towards the human ASCT-2 transporter. Both compounds had a low affinity towards the rat ASCT-2 transporter. These results were endorsed by the in vivo experiments with low uptake of both tracers in the F98 rat xenograft, low uptake of [(18)F]FBPG in the mice PC-3 xenograft and a moderate uptake of [(18)F]FPG in the PC-3 tumors. CONCLUSION: We investigated the imaging potential of two novel PET radiotracers [(18)F]FPG and [(18)F]FBPG. [(18)F]FPG is the first example of a glutamine radiotracer derivatized with a phenyl group which enables the exploration of further derivatization of the phenyl group to increase the affinity and imaging qualities. We hypothesize that increasing the affinity of [(18)F]FPG by optimizing the substituents of the arene ring can result in a high-quality glutamine-based PET radiotracer. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: We hereby report novel glutamine-based PET-tracers. These tracers are tagged on the arene group with fluorine-18, hereby preventing in vivo defluorination, which can occur with alkyl labelled tracers (e.g. (2S,4R)4-[(18)F]fluoroglutamine). [(18)F]FPG shows clear tumor uptake in vivo, has no in vivo defluorination and has a straightforward production. We believe this tracer is a good starting point for the development of a high-quality tracer which is useful for the clinical visualization of the glutamine transport

Recombinant peptide fusion proteins enable palladium nanoparticle growth

The soluble fraction of bacterial lysates containing repeat units of a metal binding domain (Pd4) fused to the carrier protein Green Fluorescent Protein (GFPuv) was used to direct palladium nanoparticle synthesis on the order of 2 nm. Characterization confirmed the synthesis of highly ordered materials, as evident by microscopy and elemental analysis, demonstrating the fact that crude bacterial lysates containing fusion peptides may be used in lieu of expensive, pure peptide

Covalent Organic Frameworks for the Capture, Fixation, or Reduction of CO2

Covalent organic frameworks (COFs) are porous crystalline organic polymers which have been the subject of immense research interest in the past 10 years. COF materials are synthesized by the covalent linkage of organic molecules bonded in a repeating fashion to form a porous crystal that is ideal for gas adsorption and storage. Chemists have strategically designed COFs for the purpose of heterogeneous catalysis of gaseous reactants. Presented in this critical review are efforts toward developing COFs for the sequestration of CO2 from the atmosphere. Researchers have determined the CO2 adsorption capabilities of several COFs is competitive with the highest surface area materials. Engineering the pore environment of COFs with chemical moieties that interact with CO2 have increased the CO2 adsorption performance. The installation of CO2 binding moieties in the COF has made possible the selective adsorption of CO2 over other gases such as N2. The high degree of control of internal pore composition in COFs is coupled with high CO2 adsorption to develop heterogeneous catalysts for the conversion of CO2 to value added products. Two notable examples of this catalysis are the fixation of CO2 to epoxides for the synthesis of cyclic carbonates and the reduction of CO2 to CO. Recent examples of COFs for the capture of CO2 will be discussed followed by COF catalysts which use CO2 as a feedstock for the production of value-added products

Cycloplatinated(II) Complexes Bearing 1,1′-Bis(diphenylphosphino)ferrocene Ligand: Biological Evaluation and Molecular Docking Studies

In this study, the cytotoxic activities of structurally related cycloplatinated(II) complexes containing chelating and bridging 1,1′-bis(diphenylphosphino)ferrocene (dppf) ligand derived from a wide range of C^N cyclometalating ligands (vpy = deprotonated 2-vinylpyridine, bzq = deprotonated benzo[h]quinoline, bpy = deprotonated 2,2′-bipyridine, bpyO = deprotonated 2,2′-bipyridine N-oxide, and ppy = deprotonated 2-phenylpyridine), were evaluated against human lung (A549), ovarian (SKOV3) and breast (MCF-7) cancer cell lines. The most cytotoxic compounds, 2a, 2c and 2d, effectively produced cell death by inducing apoptosis in the A549, SKOV3 and MCF-7 cancer cell lines. In addition, the molecular docking simulation was performed to determine the specific binding mode and the orientation of binding to DNA. According to the results of biological evaluation, the dppf-containing cycloplatinated(II) complexes exhibited strong interactions with DNA as well as high cytotoxicity and apoptosis-inducing activities to human cancer cell line. The present study suggests that precise rational design of new platinum-based complexes would result in the preparation of potential anticancer drugs, which can induce facile apoptosis

Nano-2-(dimethylamino)-N-(silica-n-propyl)-N,N-dimethylethanaminium chloride as a novel basic catalyst for the efficient synthesis of pyrido[2,3-d:6,5-d′]dipyrimidines

This study describes the synthesis and characterization of nano-2-(dimethylamino)-N-(silica-n-propyl)-N,N-dimethylethanaminium chloride {nano-[DMSPDE][Cl]}, and its application as a highly effective, heterogeneous and recyclable basic catalyst for the promotion of a useful organic reaction. The catalyst was characterized using FT-IR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) and energy-dispersive X-ray spectroscopy (EDS) methods. The nanocatalyst was successfully used to facilitate the solvent-free preparation of pyrido[2,3-d:6,5-d′]dipyrimidines by the multi-component reaction of 2-thiobarbituric acid, arylaldehydes and ammonium acetate. Nano-[DMSPDE][Cl] furnished the products in high yields and in short reaction times, and showed no significant loss of activity after multiple runs. It is noteworthy that, in the literature, pyrido[2,3-d:6,5-d′]dipyrimidines have been synthesized using Lewis or acidic catalysts; however, in this work, a basic catalyst has been applied for their preparation

Micro-flow Nanocatalysis: Synergic Effect of TfOH@SPIONs and Micro-flow Technology as an Efficient and Robust Catalytic System for the Synthesis of Plasticizers

The combination of continuous flow technology with immobilizing of only 0.13 mol% of triflic acid (TfOH) on silica-encapsulated superparamagnetic iron oxide nanoparticles (SPIONs) under solvent-free conditions successfully provided a powerful, efficient, and eco-friendly route for the synthesis of plasticizers. The turnover frequency value in micro-flow conditions varied in the range of 948.7 to 7384.6 h−1 compared to 403.8 to 3099 h−1 for in-flask. This technique works efficiently, encouraging future applications of micro-flow nano-catalysis in green chemistry

(Benzyl isocyanide)gold(I) pyrimidine‐2‐thiolate complex: Synthesis and biological activity

The reaction of [(Me2S)AuCl] with an equimolar amount of benzyl isocyanide (PhCH2NC) ligand led to the formation of complex [(PhCH2NC)AuCl] (1). The solid‐state structure of 1 was determined using the X‐ray diffraction method. Through a salt metathesis reaction, the chloride ligand in 1 was replaced by pyrimidine‐2‐thiolate (SpyN−) to afford the complex [(PhCH2NC)Au(η1‐S‐Spy)] (2), which was characterized spectroscopically. The cytotoxic activities of 1 and 2 were evaluated against three human cancer cell lines: ovarian carcinoma (SKOV3), lung carcinoma (A549) and breast carcinoma (MCF‐7). Complex 2 showed higher cytotoxicity than cisplatin against SKOV3 and MCF‐7 cancer cell lines. It showed a strong anti‐proliferative activity with IC50 of 7.80, 6.26 and 6.14 μM, compared with that measured for cisplatin which was 7.62, 12.36 and 11.47 μM, against A549, SKOV3 and MCF‐7 cell lines, respectively. The induction of cellular apoptosis by 2 was also studied on MCF‐7 cell line. Our results indicated that 2 could induce apoptosis in cancerous cells in a dose‐dependent manner