Journal of labelled compounds & radiopharmaceuticals最新文献

Triazolinediones are an important class of derivatization agents that have found application in various research disciplines. Their unique reactivity often allows precise and selective tagging of relevant molecular scaffolds to facilitate structural elucidation, tracking in biological systems, and stabilization of labile compounds. Recent research efforts mainly focused on the development of novel fluorescent and ionizable or isotopically labeled tags improving the quantification and identification of the parent molecule by suitable analytical methods. However, these concepts often lack the ability to improve properties facilitating the analysis by nuclear magnetic resonance (NMR) spectroscopy. We herein describe the first synthesis of ¹³C and ¹⁵N labeled [3,5-¹³C₂,4-¹⁵ N]4-phenyl-1,2,4-triazoline-3,5-dione utilizing the Cookson/Zinner–Deucker synthesis of urazoles. The introduced isotopic labels are ideally suited to support the structural elucidation of unknown and complex derivatization mixtures by NMR, thereby exploiting the increased sensitivity of detecting long-range J_HC and additional J_CC and J_CN couplings within the derivatized compounds of interest.

A labeling technique was developed for the imidazoline I₂ receptor ligand 2-(3-fluoro-tolyl)-4, 5-dihydro-1H-imidazole (FTIMD) using Pd(0)-mediated ¹¹C-carbomethoxylation with [¹¹C]CO, followed by imidazoline ring formation with ethylenediamine-trimethylaluminium (EDA-AlMe₃). To achieve this, [¹¹C]CO was passed through a methanol (MeOH) solution containing 3-fluoro-4-methylphenylboronic acid (1), palladium (II) acetate (Pd [OAc]₂), triphenylphosphine (PPh₃), and p-benzoquinone (PBQ). The mixture was then heated at 65°C for 5 min. EDA was introduced into the reaction mixture, and MeOH was completely evaporated at temperatures exceeding 100°C. The dried reaction mixture was combined with an EDA-AlMe (1:1) toluene solution and heated at 145°C for 10 min. Portions of the reaction mixture were analyzed through high-performance liquid chromatography, resulting in [¹¹C]FTIMD with 26% (n = 2) decay-corrected radiochemical yield (RCY). This method could be utilized for various arylborons to produce [2-¹¹C]imidazolines 4a–h with RCYs ranging from low to moderate. Notably, [2-¹¹C]benazoline was obtained with a moderate RCY of 65%. The proposed technique serves as an alternative to the Grignard method, which uses [¹¹C]CO to generate a [2-¹¹C]-labeled imidazoline ring.

The veterinary drug nitrofurazone (5-nitro-2-furaldehyde semicarbazone) exhibits excellent antimicrobial properties but its application in food-producing animals is prohibited. The illegal use of nitrofurazone is regularly monitored by food regulatory agencies. Currently, semicarbazide (SEM) is used as a marker of nitrofurazone exposure. However, the use of SEM as a marker of nitrofurazone is under scrutiny after evidence of a high incidence of false positive tests. To overcome the current dilemma, it is necessary to identify a nitrofurazone-specific marker analyte which requires conducting nitrofurazone metabolism studies in food-producing animals. The use of carbon-14 labeled nitrofurazone would facilitate metabolism studies and structural elucidation of nitrofurazone metabolites of possible utility as a marker compound. In the present work, a synthetic method is described to procure radiolabeled nitrofurazone that incorporates ¹⁴C- carbon at the semicarbazide moiety. The method incorporates ¹⁴C-carbon via employing readily available and more economically affordable [¹⁴C]-urea compared with [¹⁴C]-semicarbazide. To the best of our knowledge, there is no report on the synthesis of 5-nitro-2-furaldehyde [¹⁴C]-semicarbazone from ¹⁴C-urea. The developed method involves monoamination of [¹⁴C]-urea followed by a condensation reaction with 5-nitro-2-furaldehyde to produce 5-nitro-2-furaldehyde [¹⁴C]-semicarbazone in 85% yield with greater than 98% radiochemical purity.

Fast and straightforward incorporation of radionuclides into pharmaceutically relevant molecules is one of the main barriers to preclinical and clinical tracer research. Late-stage direct incorporation of cyclotron-produced [¹¹C]CO₂ to afford carbon-11-labeled radiopharmaceuticals has the potential to provide ready-to-inject positron emission tomography agents in less than an hour. The present work describes photocatalyzed carboxylation of alkylbenzene derivatives to afford ¹¹C-phenylacetic acids. Reaction conditions and scope are investigated followed by application of this methodology to the preparative radiosynthesis of [¹¹C]fenoprofen, a nonsteroidal anti-inflammatory drug.

Acetaminosalol labeling reaction with technetium-99m was optimized, and the radiocomplex was obtained in a high radiochemical yield of 98.9 ± 0.6% and high stability (>30 h). The tracer was characterized, and its binding to the PPARγ receptor was assessed in silico. To reduce radiation exposure to non-target organs and increase accumulation in the colon, the tracer was formulated as pH-sensitive microspheres with a mean particle size of 201 ± 2.1 μm, a polydispersity index of 0.18, a 25.3 ± 3.6 zeta potential, and 98.6 ± 0.33% entrapment efficiency. The system suitability was assessed in vivo in normal and ulcerative rats, and the biodistribution profile in the colon showed 56.5 ± 1.4% localization within 4 h. Blocking study suggested the selectivity of the tracer to the target receptor. Overall, the reported data encouraged the potential use of the labeled microspheres to target ulcerative colitis.

The α4β2 nicotinic acetylcholine receptor (nAChR) ligand 2-[¹⁸F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ([¹⁸F]nifene) has been synthesized in 10% decay-corrected radiochemical yield using the IBA Synthera® platform (IBA Cyclotron Solutions, Louvain-la-Neuve, Belgium) with an integrated fluidic processor (IFP). Boc-nitronifene served as the precursor, and 20% trifluoroacetic acid (TFA) was used to deprotect the Boc-group after radiolabeling. By omitting the solvent extraction step after radiolabeling, the process was simplified to a single step with no manual intervention. [¹⁸F]Nifene was obtained in decay-corrected radiochemical yields of 10 ± 2% (n = 20) and radiochemical purity >99%. Typical specific radioactivities of 2700–4865 mCi/μmole (100–180 GBq/μmol) were measured at the end of synthesis; total synthesis times were about 1 h 40 min.

Nanobodies (Nbs) hold significant potential in molecular imaging due to their unique characteristics. However, there are challenges to overcome when it comes to brain imaging. To address these obstacles, collaborative efforts and interdisciplinary research are needed. This article aims to raise awareness and encourage collaboration among researchers from various fields to find solutions for effective brain imaging using Nbs. By fostering cooperation and knowledge sharing, we can make progress in overcoming the existing limitations and pave the way for improved molecular imaging techniques in the future.

The tyrosine kinase MET (hepatocyte growth factor receptor) is activated or mutated in a wide range of cancers and is often correlated with a poor prognosis. Precision medicine with positron emission tomography (PET) can potentially aid in the assessment of tumor biochemistry and heterogeneity, which can prompt the selection of the most effective therapeutic regimes. The selective MET inhibitor PF04217903 (1) formed the basis for a bioisosteric replacement, leading to the deoxyfluorinated analog [¹⁸F]2. [¹⁸F]2 could be synthesized with a “hydrous fluoroethylation” protocol in 6.3 ± 2.6% radiochemical yield and a molar activity of >50 GBq/μmol. In vitro autoradiography indicated that [¹⁸F]2 selectively binds to MET in PC3 tumor tissue, and in vivo biodistribution in mice showed predominantly a hepatobiliary excretion along with a low retention of radiotracer in other organs.

We, herein, report the synthesis of ¹³C₂-labeled natural products from the mugineic acid and avenic acid family. These phytosiderophores (“plant iron carriers”) are built up from non-proteinogenic amino acids and play a key role in micronutrient uptake in gramineous plants. In this work, two central building blocks are prepared from labeled starting materials (¹³C₂-bromoacetic acid, ¹³C₂-glycine) and further employed in our recently reported divergent, branched synthetic strategy delivering eight isotopically labeled phytosiderophores. The required labeled building blocks (¹³C₂-l-allylglycine and a related hydroxylated derivative) were prepared via enantioselective phase-transfer catalysis and enantio- and diastereoselective aldol condensation with a chiral auxiliary, respectively, both potentially valuable themselves for other synthetic routes toward labeled (natural) products.

Nucleophilic copper-mediated radioiodination (CMRI) of organoboronic precursors with radioiodides is a promising method of radioiodination. The previously reported CMRI has demonstrated its great potential and scope of labeling for the radiosynthesis of radioiodine-labeled compounds. However, the reported protocols (using a small amount/volume of radioactivity) are practically not reproducible in large-scale CMRI, in which the radioactivity was usually provided in a bulk alkaline solution. A large amount of water and a strong base are incompatible with CMRI. To overcome these issues in large-scale CMRI, we have developed a simple protocol for large-scale CMRI. The bulk water was removed under a flow of inert gas at 110°C, and the strong base (i.e., NaOH) was neutralized with an acid, pyridinium p-toluenesulfonate or p-toluenesulfonic acid. In the model reactions of [¹²³I]KX-1, a PARP-1 radioligand for Auger radiotherapy, radiochemical conversions were significantly improved after neutralization of the base, and the addition of additional acids was tolerated and favorable for the reactions. Using this protocol, [¹²³I]KX-1 was radiosynthesized from 20 mCi (0.74 GBq) of [¹²³I]iodide in high radiochemical yields, high radiochemical purity, and high molar activity. This protocol should be applicable to the radiosynthesis of other compounds with radioiodine via CMRI.