Journal of labelled compounds & radiopharmaceuticals最新文献

A safe and economical synthetic method for one new carbon-14 labelled 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-[¹⁴C-pyrazolo]-1Hpyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one, [¹⁴C-pyrazolo]-Ibrutinib (2) was prepared with [¹⁴C]-barium carbonate as starting material, achieving a total yield of 19% with radiochemical and chemical purities exceeding 98%. The synthesis pathway was compared with existing methods, particularly those described in Janssen's patent applications, which offer higher yields but with more complex synthetic processes and lower purity. Despite the existing literature reporting the synthesis of ¹³C-labelled Ibrutinib, the ¹⁴C labelled method described here provides a viable alternative, particularly in some application fields necessitating the radioactive isotopic tracer technique. This work underscores the ongoing need for improved synthetic routes that offer higher yields, milder reaction conditions, and lower costs in light of the growing interest in Ibrutinib due to its clinical efficacy and commercial potential.

Carbon-11 (¹¹C)-labeled radiotracers are invaluable tools in positron emission tomography (PET), enabling real-time visualization of biochemical processes with high sensitivity and specificity. Among the various ¹¹C synthons, cyclotron-produced [¹¹C]CO₂ is a fundamental precursor, though its direct incorporation into complex molecules has traditionally been limited by its low reactivity, gaseous form, and short half-life. Recent advances in [¹¹C]CO₂ fixation chemistry through both nonphotocatalytic and photocatalytic methods have significantly expanded its utility in the synthesis of structurally diverse compounds, including carboxylic acids, carbonates, carbamates, amides, and ureas. This review summarizes key developments in [¹¹C]CO₂ radiolabeling strategies, with critical evaluation of substrate scope, radiochemical yield, molar activity, and clinical translation potential. These advances collectively expand the synthetic versatility of [¹¹C]CO₂ and pave the way for the development of structurally diverse and clinically translatable PET imaging agents.

A peptide-based, hypoxia-inducible factor-1 α (HIF-1α) specific PET tracer for tumor hypoxia imaging is reported. It was prepared with a rapid Al¹⁸F labeling method with high stability. Al¹⁸F-CLLFVY specifically binds to HIF-1α with high affinity and shows higher uptake in cells under hypoxia. Al¹⁸F-CLLFVY demonstrated comparable tumor uptake to ¹⁸F-FMISO and better contrast.

(S,S)-2-(α-(2-[¹⁸F]Fluoro[dideutero]methoxyphenoxy)benzyl)morpholine ([¹⁸F]FMeNER-D₂), which is used to image the norepinephrine transporter in the brain via positron emission tomography (PET), is typically radiosynthesized by O-fluoromethylating norethylreboxetine (NER) with [¹⁸F]bromofluoromethane-d₂ using a fully automated ¹⁸F-labeling synthesizer with a two-pot unit. We simplified the automated radiosynthesis of [¹⁸F]FMeNER-D₂ through the use of a straightforward one-pot method to prepare [¹⁸F]fluoromethyl-d₂-tosylate as the fluoromethylating agent (avoiding the need to azeotropically dry [¹⁸F]F⁻ in advance), which was then reacted with NER. The reaction conditions were optimized, with [¹⁸F]FMeNER-D₂ synthesized using an ¹⁸F-labeling synthesizer equipped with a one-pot unit. As a result, a synthesis time, radiochemical yield based on total [¹⁸F]F⁻, molar activity, and radiochemical purity of 66 ± 4.7 min (n = 7), 9.0% ± 0.8% (n = 3), 130–275 GBq/μmol (n = 7), and > 97% (n = 7), respectively, were obtained at the end of synthesis. In conclusion, we successfully synthesized [¹⁸F]FMeNER-D₂ using a simplified one-pot, fully automated, ¹⁸F-fluoromethylation method in an ¹⁸F-labeling synthesizer.

In the present study, the influence of activated carbon (AC) on mineralization, degradation, extractable residues, and bound residue formation of ¹⁴C-sulfamethoxazole and ¹⁴C-acetaminophen was investigated. The results showed that AC facilitated the dissipation of ¹⁴C-sulfamethoxazole and ¹⁴C-acetaminophen and their formation of bound residue and exerted a significant inhibitory effect on their mineralization. The addition of 0.05%–2% AC showed an extraordinarily strong adsorption capacity of acetaminophen with K_d values of 47.2–409.8 times higher than that in the nonamended soil, as compared with 21.0–2273.4 times for sulfamethoxazole. An inverse relationship was found between sorption strength and mineralization or degradation kinetics. The effect of AC was likely due to its higher organic carbon (OC) content and the enhancement of surface areas and pore volumes where additional sites might be provided for binding or conjugation interactions with sulfamethoxazole or acetaminophen or their transformation products. Results from the present study clearly highlighted the significance of AC for influencing the fate of sulfamethoxazole and acetaminophen and stressed that sorption was potentially a critical factor in controlling the fate processes in soil.

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.