Journal of labelled compounds & radiopharmaceuticals最新文献

The synthesis of tritium-labelled glycine transporter 1 inhibitor Org24598 is reported. Because of the instability of the Org24598 skeleton under hydrogenation conditions, a synthetic approach using an in-house prepared tritium-labelled alkylating agent ([³H]MeI, SA = 26.2 Ci/mmol) was employed. Alternative methods of labelling are discussed.

[1′-¹³C]Citric acid (1) was efficiently prepared from dimethyl 1,3-acetonedicarboxylate in two steps as a probe for a breath test. The synthetic method was selected because of the yield and reproducibility. Compound 1 was orally administrated to rats, and the time course of the increase of ¹³CO₂/¹²CO₂ ratios (Δ¹³CO₂) in their breath was successfully followed, indicating the metabolism of 1. Thus, the ¹³C-breath test using 1 is a promising method to evaluate tricarboxylic acid (TCA) cycle flux.

The σ-1 receptor is a non-opioid transmembrane protein involved in various human pathologies including neurodegenerative diseases, inflammation, and cancer. The previously published ligand [¹⁸F]FTC-146 is among the most promising tools for σ-1 molecular imaging by positron emission tomography (PET), with a potential for application in clinical diagnostics and research. However, the published six- or four-step synthesis of the tosyl ester precursor for its radiosynthesis is complicated and time-consuming. Herein, we present a simple one-step precursor synthesis followed by a one-step fluorine-18 labeling procedure that streamlines the preparation of [¹⁸F]FTC-146. Instead of a tosyl-based precursor, we developed a one-step synthesis of the precursor analog AM-16 containing a chloride leaving group for the S_N2 reaction with ¹⁸F-fluoride. ¹⁸F-fluorination of AM-16 led to a moderate decay-corrected radiochemical yield (RCY = 7.5%) with molar activity (A_m) of 45.9 GBq/μmol. Further optimization of this procedure should enable routine radiopharmaceutical production of this promising PET tracer.

One of the key strategies for radiochemical research facilities is the automation of synthesis processes. Unnecessary manual operations increase the radiation exposure of personnel, while simultaneously threatening the reliability of syntheses. We have previously reported an affordable open-source system comprising 3D-printed continuous flow reactors, a custom syringe pump, and a pressure regulator that can be used to perform radiofluorinations. In this paper, we address additional essential processes that are needed for radiotracer development and synthesis, with the aim of making laboratory work safer and research more efficient. We have designed and evaluated a fully automated system for rapidly and effectively processing and drying aqueous [¹⁸F]fluoride that can be directly connected to the cyclotron. This process relies on triflyl fluoride gas generation and allows nucleophilic [¹⁸F]fluoride to be prepared safely in a hotcell within 10 min and an activity recovery of 91.7 ± 1.6% (n = 5). Owing to the need for convenient radiofluorinated prosthetic ligands, we have adapted our continuous flow system to produce [¹⁸F]fluoroethyl tosylate (FEOTs) and [¹⁸F]fluoroethyl triflate (FEOTf), prosthetic groups that are widely used for late-stage fluoroethylation of PET tracers. The processes as well as the radiolabeling of different groups are compared and comprehensively discussed. Having a method providing [¹⁸F]fluoroethyl tosylate (FEOTs) as well as [¹⁸F]fluoroethyl triflate (FEOTf) quickly and highly efficiently is beneficial for radiochemical research.

Riboflavin (RF, vitamin B2) plays a key role in metabolic oxidation–reduction reactions, especially in the mitochondrial reprogramming of energy metabolism. Riboflavin transporter 3 (RFVT3) is a vital section of the mitochondrial network and involved in riboflavin homeostasis and production of adenosine triphosphate (ATP). The abnormal expression of RFVT3 is closely associated with the occurrence and progression of multiple diseases. Therefore, it is vital to understand the riboflavin internalization pathway under pathological conditions by addressing the abnormal expression of RFVT3, which could be a highly valuable biomarker for the early diagnosis and effective therapy of various diseases.

Primary aldosteronism (PA) is the leading secondary cause of hypertension. Determining whether one (unilateral) or both (bilateral) adrenal glands are the source of PA in a patient remains challenging, and yet it is a critical step in the decision whether to recommend potentially curative surgery (adrenalectomy) or lifelong medical therapy (typically requiring multiple drugs). Recently, we have developed a fluorine-18 radiopharmaceutical [¹⁸F]CETO to permit greater access to PA molecular imaging. Herein, we report an automated synthesis of this radiotracer. To manufacture the radiopharmaceutical routinely for clinical PET studies, we implemented an automated radiosynthesis method on a Synthra RNplus© synthesiser for which Cl-tosyletomidate was used as the precursor for radiolabelling via nucleophilic [¹⁸F]fluorination. [¹⁸F]CETO was produced with 35 ± 1% (n = 7), decay corrected and 25 ± 4% (n = 7) non-decay corrected radiochemical yield with molar activities ranging from 150 to 400 GBq/μmol. The GMP compliant manufacturing process produces a sterile formulated [¹⁸F]CETO injectable solution for human use as demonstrated by the results of quality control. Automation of the radiosynthesis of [¹⁸F]CETO should facilitate uptake by other adrenal centres and increase access to molecular imaging in PA.

AZD4747 is a KRAS^G12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [¹¹C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [¹¹C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

Carbon-11 (¹¹C) is a widely used radionuclide for positron emission tomography (PET) owing to the omnipresence of carbon atoms in organic molecules. While its half-life of 20.4 min is ideal for imaging and dosimetry, it also limits the synthetic possibilities. As such, the development of fast and easy, high-yielding synthesis methods is crucial for the application of ¹¹C-labeled tracers in humans.

In this study, we present a novel and efficient method for the reaction of [¹¹C]CO₂ with amine precursors using benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP) to access ¹¹C-labeled ureas. Our method is extremely fast as it only requires transfer of [¹¹C]CO₂ into a solution with precursor and BOP at room temperature, where it reacts momentary into the desired ¹¹C-labeled urea. This simple procedure makes it possible to radiolabel urea directly from [¹¹C]CO₂ without the need for advanced equipment, making the method applicable for all laboratories where [¹¹C]CO₂ is available. We synthesized a small series of aliphatic symmetrical and non-symmetrical ¹¹C-labeled ureas using this method, and achieved good to excellent yields.

The novelty of our study lies in the fact that peptide coupling reagent BOP is used for the first time in radiochemistry to activate [¹¹C]CO₂, facilitating its reaction with amines to obtain ¹¹C-labeled ureas.

The synthesis of a ¹⁴C-labeled C-18 functionalized steroid (as referred as EM-6798) that will serve as a probe for the research of novel antiandrogens has been accomplished. This radioactive steroid was obtained in nine steps by coupling racemic N-cyclohexyl-1-(3′-hydroxy[U-¹⁴C]phenyl)propylamine with protected 18-bromomethyl-3,17-androstenedione. Incorporation of the radiolabel on the C-18 side chain was achieved using commercially available 3-bromo[U-¹⁴C]phenol. Alkylation of N-cyclohexyl-1-(3′-hydroxy[U-¹⁴C]phenyl)propylamine with 3-ethylenedioxy-18-bromomethyl-3,17-androstenedione furnished after reduction and deprotection, [phenyl-U-¹⁴C]EM-6798 in a 20% overall yield from 3-bromo[U-¹⁴C]phenol at a specific activity of 156 μCi/mg with 97.9% radiochemical purity as determined by HPLC.

Nitrofurazone usage in food-producing animals is prohibited in most countries, including the United States. Regulatory agencies regularly monitor its use in domestic, export/import animals' food products by measuring the semicarbazide (SEM) metabolite as a biomarker of nitrofurazone exposure. However, the use of SEM is controversial because it is also produced in food naturally and thus gives false positive results. A cyano-metabolite, 4-cyano-2-oxobutyraldehyde semicarbazone (COBS), is proposed as an alternate specific marker of nitrofurazone to distinguish nitrofurazone from treated or untreated animals. A synthetic method was developed to produce COBS via metallic hydrogenation of nitrofurazone. The product was isolated and characterized by one- and two-dimensional nuclear magnetic spectroscopy (NMR) experiments, Fourier-transform infrared spectroscopy (FT-IR), and mass spectrometry. The developed synthetic procedure was further extended to synthesize isotopically labeled 4-[¹³C]-cyano-2-oxo- [2, 3, 4-¹³C₃]-butyraldehyde semicarbazone. Labeled COBS is useful as an internal standard for its quantification in food-producing animals. Thus, the developed method provides a possibility for its commercial synthesis to procure COBS. This is the first synthesis of the alternate specific marker metabolite of nitrofurazone for possible usage in regulatory analysis to solve a real-world problem.