Journal of labelled compounds & radiopharmaceuticals最新文献

A synthesis of N-monodeuteriomethyl-2-substituted piperidines is described. An efficient and readily scalable anodic methoxylation of N-formylpiperidine in an undivided microfluidic electrolysis cell delivers methoxylated piperidine 3, which is a precursor to a N-formyliminium ion and enables C-nucleophiles to be introduced at the 2-position. The isotopically labelled N-deuteriomethyl group is installed using the Eschweiler–Clarke reaction with formic acid-d₂ and unlabelled formaldehyde. Monodeuterated N-methyl groups in these molecular systems possess small isotropic proton chemical shift differences important in the investigation of molecules that are able to support long-lived nuclear spin states in solution nuclear magnetic resonance.

Diabetes mellitus (DM) and insulinoma are mainly affected by the status of pancreatic β-cell mass (BCM). Development of imaging agents for BCM allows to study pancreatic β cells and the relationship between β cells and DM or insulinoma. In this study, we investigated the density of dopamine D₁ receptor on the β cells and measured BCM by statistical image processing. The pancreatic uptakes of [¹²⁵I]I-R-(+)-7-chloro-8-hydroxy-1-(3′-iodopheny1)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([¹²⁵I]I-R-(+)-TISCH), dopamine D₁ receptor tracer, in normal and diabetic rats displayed significant differences at 30 min (1.11 ± 0.08% ID/g vs. 0.63 ± 0.09% ID/g, p < 0.0001). In the presence of SCH23390, the pancreatic uptake of [¹²⁵I]I-R-(+)-TISCH at 30 min in normal rats was lower (1.01 ± 0.04% ID/g, p < 0.05). Although the blocking was not complete, [¹²⁵I]I-R-(+)-TISCH showed specific binding signals to the pancreas. Furthermore, the uptakes of [¹²⁵I]I-R-(+)-TISCH in INS-1 cells were reduced in the presence of SCH23390 at different concentrations. [¹²⁵I]I-R-(+)-TISCH displayed a respectable uptake in insulinoma. Overall, [¹²⁵I]I-R-(+)-TISCH provided specific binding signals to pancreatic β cells. Although the specific signal may not be sufficient for imaging in vivo, the dopamine D₁ receptor can still be considered as a potential target for studying BCM. Further investigation will be required to optimize the ligand.

[¹⁸F]SynVesT-1 (also known as [¹⁸F]SDM-8 or [¹⁸F]MNI-1126) is a potent and selective synaptic vesicle glycoprotein 2 (SV2A) positron emission tomography (PET) imaging agent. In order to fulfill the increasing clinical demand of an ¹⁸F-labeled SV2A PET ligand, we have developed a fully automated procedure to provide a sterile and pyrogen-free good manufacturing procedure (GMP)-compliant product of [¹⁸F]SynVesT-1 suitable for clinical studies in humans. [¹⁸F]SynVesT-1 is synthesized via a rapid copper-mediated radiofluorination protocol. The procedure was developed and established on a commercially available module, TracerMaker (ScanSys Laboratorieteknik ApS, Copenhagen, Denmark), a synthesis platform originally developed to conduct carbon-11 radiochemistry. From ~130 GBq (end-of-bombardment), our newly developed procedure enabled us to prepare [¹⁸F]SynVesT-1 in an isolated radioactivity yield of 14,220 ± 800 MBq (n = 3), which corresponds to a radiochemical yield (RCY) of 19.5 ± 0.5%. The radiochemical purity (RCP) and enantiomeric purity of each of the final formulated batches exceeded 98%. The overall synthesis time was 90 min and the molar activity was 330 ± 60 GBq/μmol (8.9 ± 1.6 Ci/μmol). The produced [¹⁸F]SynVesT-1 was stable over 8 h at room temperature and is suitable for in vivo PET imaging studies in human subjects.

In this concise practitioner protocol, the radiochemical synthesis of 2′-deoxy-2′-[¹⁸F]fluoro-9-β-d-arabinofuranosylguanine ([¹⁸F]FAraG) suitable for human positron emission tomography (PET) studies is described and the results from validation productions are presented. The high specific activity (sometimes referred to as molar activity) radiotracer product is prepared as a sterile, apyrogenic solution that conforms to current Good Manufacturing Practice (cGMP) requirements established by the U.S. Food and Drug Administration.

Fast and reasonable low-scale (200 nmol) syringe-made synthesis of ¹⁵N-labeled oligonucleotides representing DNA trinucleotide codons is communicated. All codons were prepared by solid-phase controlled pore glass synthesis column technique via the phosphoramidite method. Twenty-four labeled oligonucleotides covering the DNA genetic code alphabet were prepared using commercially available reagents and affordable equipment in a reasonably short period of time, with acceptable yields and purity for direct applications in mass spectrometry.

In this practitioner protocol, the optimization of the radiochemical synthesis of [¹⁸ F]fluoroestradiol (FES) on the Synthra RNplus research automated platform is described in detail and a quality control (QC) summary of three validation productions is presented. In comparison with published synthesis methods developed on other platforms, the yield was considerably improved (40%-45% ndc). The other important improvement is the reduction of the required concentration of H₂ SO₄ avoiding the production of high concentrations of acidic vapors that can deteriorate the module. Purification was achieved by solid phase extraction, and the required adaptation of an external heating plate to the module to evaporate the ethanol is also described. The product was obtained with high radiochemical purity and fulfilled all the requirements of current Good Manufacturing Practice (cGMP). The final product is formulated as a sterile, pyrogen-free solution suitable for human injection. To the best of our knowledge, this is the first report of FES production using this type of module.

Radioactive iodine isotopes play a pivotal role in radiopharmaceuticals. Large-scale production of multi-patient dose of radioiodinated nuclear medicines requires high concentration of radioiodine. We demonstrate that tetrabutylammonium chloride and methyltrioctylamonium chloride are effective phase transfer reagents to concentrate iodide-124, iodide-125 and iodide-131 from the corresponding commercial water solutions. The resulting concentrated radioiodide, in the presence of either phase transfer reagent, does not hamper the chemical reactivity of aqueous radioiodide in the copper (II)-mediated one-pot three-component click chemistry to produce radioiodinated iodotriazoles.

In this study, quality control parameters such as radiochemical yield, radiochemical purity, and in vitro stability of gallium (⁶⁸ Ga)-prostate-specific membrane antigen-11 ([⁶⁸ Ga]Ga-PSMA11) radiopharmaceutical obtained in a research laboratory with three different synthesis algorithms were evaluated and compared. Gallium (⁶⁸ Ga) chloride precursor to be used in labeling in all three methods was obtained by using ITG brand ⁶⁸ Ge/⁶⁸ Ga generator. The first method for the [⁶⁸ Ga]Ga-PSMA11 radiopharmaceutical was performed with the automated synthesis module, which is widely used in clinical practice. Its radiochemical yield, quality assurance, and stability met expectations. Radiolabeling success, suitability of quality control parameters, and in vitro stability of [⁶⁸ Ga]Ga-PSMA11 radiopharmaceutical performed with ANMI kit were examined. The final product showed success in ⁶⁸ Ga-complexation kinetics. All quality control criteria performed met the expectation for clinical applications. Direct cold labeling of PSMA11 ligand with sodium bicarbonate buffer was examined. Results were similar to the ANMI kit. Considering that all three methods are successful in radiochemical labeling, labeling with NaHCO₃ buffer shows the labeling preference when we choose the cheap, practical, and easy labeling option.

The PET tracer [¹⁸ F]F-AraG, an arabinosyl guanine analog, has shown promise for visualizing activated T cells in multiple diseases. Herein, a practitioner's protocol is described, in which the PET tracer is prepared using minimal equipment and manual actions, making it widely accessible for preclinical applications.