Journal of labelled compounds & radiopharmaceuticals最新文献

This study aimed to evaluate the targeted diagnostic imaging and therapeutic applications of SNW-1 nanoparticles. The nanoparticles were synthesized using microwave technique and characterized in terms of size, zeta potential, morphology, and chemical structure. The results demonstrated that the quasispherical and planar nanoparticles with the size of 370.4 nm and zeta potential of 0.4 mV were synthesized. Then, the nanoparticles were labeled with technetium-99m, and their in vivo biodistribution was assessed. Based on the results, the highest accumulation of the nanoparticles was observed in the bladder, liver, kidney, and heart tissues of the rabbits, respectively, while in the rat, the highest accumulation was observed in the liver, bladder, and heart tissues, respectively. In the rabbits, on average, the accumulation of the nanoparticles in the bladder was 7.4-, 8.7-, and 44.1-fold higher than that of the liver, kidney, and heart, respectively, while in the rat, the accumulation of the nanoparticles in the liver was 8.4- and 20.3-fold higher compared to that of the bladder and heart, respectively. The high bladder accumulation of the SNW-1 nanoparticles can be indicated by their high clearance, making them especially appropriate for kidney imaging and therapeutic applications.

The radiosynthesis of the systemic fungicide for oomycete disease control Benalaxyl-M and its two most relevant soil metabolites was developed from the versatile common [phenyl-U-¹⁴C]N-(2,6-dimethylphenyl)-D-alanine methyl ester intermediate 4 by reaction with Meldrum's acid and subsequent hydrolysis of the ester group. The triflate of the methyl ester of (S)-lactic acid 6 employed in the synthesis of [phenyl-U-14C]N-(2,6-dimethylphenyl)-D-alanine methyl ester allows us an optimal use of the labelled [phenyl-U-14C]2,6-dimethylaniline. The greater reactivity of the triflate of the methyl ester of (S)-lactic acid compared to the analogous p-toluenesulfonate or methanesulfonate allows the reaction to occur at room temperature with higher enantiomeric purity and better yield.

Three novel ¹⁴C-labelled isotopologues of the psychoactive agents psilocin, psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) were synthesised, all labelled at the 2-position of the indole. The syntheses involved incorporating the 3-dimethylaminoethyl substituent common to all three substances onto a 4- or 5-substituted indole intermediate via successive treatments with oxalyl chloride, dimethylamine and reduction with lithium aluminium hydride.

Psilocybin-2-¹⁴C with a specific activity of 234 μCi/mg exhibited limited stability, but a 5.5-fold radio dilution with unlabelled psilocybin afforded material that maintained a radiochemical purity exceeding 97.5% after 1-month storage at ≤ −70°C. The stability of 5-MeO-DMT-2-¹⁴C succinate salt with a specific activity of 173 μCi/mg was assessed over a more extended storage period, and after 6 months at ≤ −70°C the radiochemical purity was 98.0%, supporting its use in long-term studies.

The radiolabelled psilocybin-2-¹⁴C and 5-MeO-DMT-2-¹⁴C succinate represent new tools for in vivo pharmacokinetic and metabolic studies with psychedelic tryptamines. These novel derivatives may offer enhanced metabolic stability and facilitate more precise ADME and mass balance studies. Future research will explore their behaviour in biological systems to support necessary studies toward regulatory approval of both psilocybin and 5-MeO-DMT for treating mental health disorders such as depression, anxiety and post-traumatic stress disorder.

N-((1R,4R)-4-(3-Chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (ARV-110) is a proteolysis-targeting chimera (PROTAC) designed against the androgen receptor (AR), which shows great potential for treating AR-dependent diseases, such as prostate cancer. To support preclinical safety evaluations as well as studies of drug metabolism and pharmacokinetics, two versions of carbon-14-labeled ARV-110 were synthesized: N-((1R,4R)-4-(3-chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-[1,3-¹⁴C2]dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (¹⁴C-ARV-110-a) and N-((1R,4R)-4-(3-chloro-4-[cyano-¹⁴C]cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (¹⁴C-ARV-110-b). The synthesis of ¹⁴C-ARV-110-a was initiated from 1,2-dibromo-4,5-difluorobenzene and zinc cyanide-¹⁴C (Zn(¹⁴CN)₂), while ¹⁴C-ARV-110-b was prepared from 2-chloro-4-fluoro[cyano-¹⁴C]benzonitrile.

Deucravacitinib (BMS-986165) is a small molecule allosteric inhibitor of tyrosine kinase 2 (TYK2) currently approved for the treatment of moderate to severe plaque psoriasis. Tyrosine kinase 2 (TYK2) is a member of the Janus (JAK) family of non-receptor kinases that modulate the production of inflammatory cytokines. The synthesis of ¹⁴C-radiolabeled and stable-isotope labeled variants of deucravacitinib is described in this publication.

Fluorine-18 labeling of peptides and proteins is typically performed by an indirect labeling method. In this labeling approach, a labeled prosthetic group is prepared first and then conjugated to the proteins and peptides of interest. 6-[¹⁸F]fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester is a useful prosthetic group for indirect labeling. We have recently developed an efficient radiolabeling method, “fluorination on Sep-Pak,” that enables the preparation of this prosthetic group with high radiochemical yield and purity in under 10 min. A variety of biomolecules have been radiolabeled using this prosthetic group. The radiolabeling procedure was either manual or semiautomated. However, a fully automated synthesis method is essential for successful clinical translation. Therefore, we developed a fully automated reproducible radiolabeling method to prepare fluorine-18–labeled albumin using the Trasis AllinOne module. The procedure was completed in 50 min. The overall radiochemical yield was 25%–36% (decay-corrected, n = 6) using 1 mg of albumin with a radiochemical purity > 98%.

Angiogenesis, particularly driven by the overexpression of vascular endothelial growth factor (VEGF), plays a crucial role in the growth and metastasis of tumors, making VEGF a significant target in the diagnosis and therapy of non-small cell lung cancer (NSCLC). In this work, the potential of ^99mTc-labeled ranibizumab was investigated for the non-invasive diagnosis of NSCLC. To that end, ranibizumab (RNB), a VEGF-neutralizing antibody, was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza1,4,7,10-tetra(2-carbamoylmethyl) cyclododecane (TCMC) followed by labeling with technetium-99m (^99mTc) using different reaction parameters. The ^99mTc-TCMC-RNB was characterized in terms of the percent radiochemical purity (% RCP) up to 6 h, in vitro stability in serum up to 16 h, internalization kinetics in A549 cells, and biodistribution using the NSCLC Sprague Dawley rat model. The ^99mTc-labeled TCMC-RNB exhibited 98.3 ± 0.2% RCP in normal saline, stability in rat serum with an overall decay of 32.10% within 18 h, and specific binding to A549 NSCLC cells. Biodistribution studies showed significant tumor uptake. These findings suggest that ^99mTc-labeled TCMC-RNB holds promise as a specific imaging agent for the diagnosis and monitoring of VEGF-related malignancies, particularly in NSCLC.