Journal of labelled compounds & radiopharmaceuticals最新文献

Since first becoming commercially available in 2018, the PET radiopharmaceutical [¹⁸F]PSMA-1007 has been used widely for the diagnosis and staging of prostate cancer. A pharmacopoeia monograph first became available in 2021, prescribing a radiochemical purity specification of >91%, based on analytical results from both TLC (for [¹⁸F]fluoride impurity alone) and HPLC (for all other ¹⁸F-impurities). Though this monograph has provided clarity for the quality control testing of [¹⁸F]PSMA-1007, it prescribes a HPLC method using phosphate buffer mobile phase that may present a risk of precipitation of phosphate salts in the HPLC system. The method also requires specialised hardware not immediately available to all laboratories. This work describes the development of a simple, rapid reversed-phase HPLC method utilising 0.1 M ammonium formate mobile phase for the accurate assessment of both [¹⁸F]fluoride impurity and overall radiochemical purity in a single test. This method is especially useful for assessment of product stability over time. A more accurate TLC method for [¹⁸F]fluoride impurity is also described.

A radiochemical synthesis of [¹⁸F]DK222, a peptide binder of programmed death ligand 1 protein, suitable for human PET studies is described, and results from validation productions are presented. The high specific activity radiotracer product is prepared as a sterile, apyrogenic solution that conforms to current Good Manufacturing Practice (cGMP) requirements. In addition, the production is extended to use a commercial synthesizer platform (General Electric FASTlab 2).

We report here the detailed radiosynthesis of [¹⁸F]mG4P027, a metabotropic glutamate receptor 4 (mGluR4) PET radiotracer, which showed superior properties to the currently reported mGluR4 radiotracers. The radiosynthesis in the automated system has been challenging, therefore we disclose here the major limiting factors for the synthesis via step-by-step examination. And we hope this thorough study will help its automation for human use in the future.

Pretargeting imaging has gained a lot of prominence, due to its excellent bioorthogonality and improved imaging contrast compared to conventional imaging. A new iodo tetrazine (Tz) derivative has been synthesized and further developed into the corresponding iodine-125 (¹²⁵I) analog (12), via the trimethylstannane precursor. Radiolabeling with either N-chlorosuccinimide or chloramine-T, in either MeCN or MeOH proceeded with a radiochemical conversion (RCC) of >80%. Subsequent deprotection only proved successful, among the tested conditions, when the radiolabeled Tz was stirred in 6-M HCl_(aq.) at 60°C for 2.5 h. To the best of our knowledge, this is the first H-tetrazine labeled with iodine. In vivo investigations on the pretargeting ability of 12 are currently under way.

This paper describes the deuterium-labelling of alkylnitroaromatics by base-catalysed exchange with deuterium oxide. As the alkyl protons alpha to the aromatic ring are the most acidic sites in the molecule, regioselective hydrogen isotope exchange at this benzylic location leads to a regiospecifically deuterated product. The exchange labelling takes place in good yields and with high atom% abundance in the presence of an appropriate nitrogen base. Alkylated 2,4-dinitrobenzenes deuterate at room temperature under catalysis by triethylamine, whilst alkylated 2-nitro- or 4-nitrobenzenes and related mono-nitroaromatics require higher temperatures and catalysis by 1,5-diazobicyclo[4.3.0]non-5-ene (DBN). The labelling reactions require an inert gas atmosphere, but otherwise are simple and high yielding with no obvious byproducts. Those compounds in which the benzylic protons are in an ortho-orientation with respect to the nitro group label somewhat more slowly than the analogues where there is a para relationship. In addition, higher alkyl homologues undergo benzylic deuteration at slower rates than methyl.

Ibrutinib is an oral medication for the treatment of B cell malignancies. During its clinical development, a stable isotopologue of ibrutinib was required for the assessment of the drug's absolute oral bioavailability via intravenous microdosing. The following work describes a 10-step, gram-scale production of carbon-13 labeled ibrutinib from [¹³C₆]phenol (¹³C₆, 99%) in 31% overall yield with >99% chemical purity and >99% enantiomeric excess (ee), suitable for intravenous microdosing in humans.

In recent years, clinical imaging with ⁸⁹ Zr-based radiopharmaceuticals has been gaining significant importance in nuclear medicine. This article provides the results of a comparative study of methods for obtaining ⁸⁹ Zr solutions using ZR, Chelex-100, and TBP resins in the form of [⁸⁹ Zr]Zr-oxalate, [⁸⁹ Zr]Zr-chloride, and [⁸⁹ Zr]Zr-citrate in terms of purification and labeling efficiency. All evaluated methods allowed us to obtain ⁸⁹ Zr with high yield (>90% in 1 ml). The chemical form of ⁸⁹ Zr has a significant influence on the radiolabeling efficiency of the deferoxamine (DFO) chelator and its derivatives. Compared with [⁸⁹ Zr]Zr-oxalate, the application of [⁸⁹ Zr]Zr-chloride and [⁸⁹ Zr]Zr-citrate solutions leads to a higher efficacy of [⁸⁹ Zr]Zr-DFO complex formation. It should be noted that the sequence of mixing of the reagents during the radiolabeling reaction and the residual concentration of oxalic acid appeared to be crucial in the case of [⁸⁹ Zr]Zr-chloride. According to the experimental data, radiolabeling of DFO and its derivatives is preferable to use more stable chemical forms of ⁸⁹ Zr, such as [⁸⁹ Zr]Zr-citrate. The concept will be applied in the further studies involving antibody-based bioconjugates.

The discovery of novel imaging agents for positron emission tomography (PET) relies on medicinal chemistry best practices, including a good understanding of molecular and pharmacological properties required for the acquisition of relevant, high-quality images. This short note reviews the characteristics of a series of clinically successful imaging agents, providing guidance for the optimization of such molecular tools. PET imaging plays an important role in staging disease and in helping clinical dose selection, which is critical for the efficient development of drug candidates.

The synthesis of deuteriated tri-tert-butyl phosphine is reported. This synthesis is an adaptation of the known procedure for tri-tert-butyl phosphine via a Grignard intermediate.