Journal of labelled compounds & radiopharmaceuticals最新文献

BI 1584142 (1) and BI 1810631 (2, zongertinib) are potent and selective HER2 tyrosine kinase inhibitors being developed for the treatment of non–small cell lung cancer. Carbon-14–labeled versions of these drug candidates were needed to study their absorption, distribution, metabolism, and excretion in animals and in humans. BI 1584142 and BI 1810631 differ in two moieties; the former contains a piperazine and the latter a 4-aminopiperidine. Therefore, a common carbon-14–labeled intermediate like the sulfoxide [¹⁴C]-8 was prepared in four radioactive steps and used to provide [¹⁴C]-1 and [¹⁴C]-2 in two and three extra steps, respectively. Deuterium-labeled 1 and 2 were also synthesized as internal standards, using piperazine-d₈ and 4-aminopiperidine-d₉ for bioanalytical studies and other studies.

We describe the synthesis and preclinical assessment of a novel technetium-99m-labeled 5α-reductase (5AR) inhibitor, a 5AR-targeting drug, a target enzyme of prostate cancer (PCa) pathology, as a SPECT imaging probe. Finasteride was attached to 6-hydrazinonicotinic acid (HYNIC) with HYNIC NHS ester chemistry. The HYNIC–finasteride conjugate was identified by NMR, IR, MP analysis, high-resolution ESI MS ([M + H]+ m/z 507.3190, Δppm −3.9), and RP HPLC (Rt 13.9 min, > 98% purity). ⁹⁹ᵐTc radiolabeling using tricine/EDDA co-ligands resulted in > 98% radiochemical purity. The radiotracer was highly stable in vitro (> 91% in PBS at 4 h; ≥ 68% in serum at 16 h) and had a logP value of −1.25 ± 0.08, with good hydrophilicity. Saturation binding assays in LNCaP cells had 5AR, with Kd and Bmax values of 3.10 ± 0.7 nM and 82.44 ± 3.2 fmol/10⁶ cells. Biodistribution studies in LNCaP xenograft-bearing mice showed high tumor uptake (5.62% ± 0.32% ID/g at 4 h), which reduced in blocked groups (1.25% ± 0.18% ID/g). SPECT images offered selective tumor accumulation with good tumor-to-normal tissue contrast and renal clearance in tumor-bearing rabbits. These findings suggest that ⁹⁹ᵐTc-HYNIC–finasteride is a promising SPECT radiotracer for noninvasive 5AR imaging in PCa.

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.