Synthesis of the key building block, 2-thiophenemethanamine-H hydrochloride, was achieved using mild conditions and purification methods in three steps from commercially available thiophene-H, with an overall yield of 61.6% and an overall isotopic enrichment of 87.6%. 2-thiophenemethanamine-H hydrochloride has the potential to be a useful intermediate in the synthesis of isotopically labelled compounds of pharmaceutical interest.

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 [C]-8 was prepared in four radioactive steps and used to provide [C]-1 and [C]-2 in two and three extra steps, respectively. Deuterium-labeled 1 and 2 were also synthesized as internal standards, using piperazine-d and 4-aminopiperidine-d for bioanalytical studies and other studies.

In order to reduce the development of antibiotic and chemical resistance in bacterial phytopathogens like Ralstonia solanacearum, which causes bacterial wilt disease, bacteriophages are a safe and efficient biocontrol method. This research will explore how to use radioisotopes to track the bacteriophage absorption by plants from roots to leaves as a means for improving phage persistence and thereby the control of bacterial wilt disease caused by R. solanacearum. We have investigated the uptake and delivery of R. solanacearum-specific bacteriophages in tomato plants. Transferring phage through roots to leaves showed a gradual increase over time until reaching the maximal at 120 min, where the percentage of bacteriophage reaches 21.95% of the total amount of the injected radiation dose, which is considered a good sign for the ability of bacteriophage to reach the leaves and infect the pathogen through its transport system if injected directly into soil. Demonstrating in-plant translocation of R. solanacearum-specific bacteriophages and their effect of reducing bacterial wilt symptoms may significantly contribute to a better control of R. solanacearum and promote further investigations on the penetration and translocation of phages into plants.

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 AlF labeling method with high stability. AlF-CLLFVY specifically binds to HIF-1α with high affinity and shows higher uptake in cells under hypoxia. AlF-CLLFVY demonstrated comparable tumor uptake to F-FMISO and better contrast.

Carbon-11 (C)-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 C synthons, cyclotron-produced [C]CO 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 [C]CO 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 [C]CO radiolabeling strategies, with critical evaluation of substrate scope, radiochemical yield, molar activity, and clinical translation potential. These advances collectively expand the synthetic versatility of [C]CO and pave the way for the development of structurally diverse and clinically translatable PET imaging agents.

A safe and economical synthetic method for one new carbon-14 labelled 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-[C-pyrazolo]-1Hpyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one, [C-pyrazolo]-Ibrutinib (2) was prepared with [C]-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 C-labelled Ibrutinib, the C 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.

As the field of radiochemistry moves toward the rapid development and translation of radiopharmaceuticals, the radiosynthetic methodology and manufacturing are becoming more and more refined. As the use of radiopharmaceuticals in clinical research is one of the primary goals of radiochemistry research, compliance with cGMP regulations is a key factor in radiosynthesis developments. This review is primarily focused on the automation of the radiosynthesis on modules, with a special focus on the use of disposable cassettes for the reactors and flow-paths. This review aims to cover the developments and current state-of-the-art for cassette-based radiosynthesis of carbon-11 radiopharmaceuticals.

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). ᵐTc 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/10 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 ᵐTc-HYNIC-finasteride is a promising SPECT radiotracer for noninvasive 5AR imaging in PCa.

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-C]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.

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.

Muscimol, a potent GABA receptor agonist and psychoactive alkaloid found in Amanita mushrooms, is widely used as a tool compound in neurochemical research. Despite its importance, synthetic access to [H]muscimol of high specific activity has remained limited due to the challenges associated with conventional labeling strategies. Herein, we report a novel synthetic approach for the preparation of [H]muscimol based on the reduction of a suitably protected amide precursor using in situ generated tritioborane (BT·THF). The precursor was synthesized in four steps from dimethyl acetylenedicarboxylate, and subsequent electrophilic reduction afforded [H]benzyl-protected muscimol in a radiochemical yield of 44 mCi (1.63 GBq) and a molar activity of 48.3 Ci/mmol (1.79 TBq/mmol). Final deprotection with HBr in acetic acid yielded [H]muscimol·HBr in > 95% radiochemical purity. The method avoids the use of bulk tritiated water employed in established synthetic protocols and enables safe, reliable, and efficient access to this valuable radioligand for applications in GABA receptor studies.

(S,S)-2-(α-(2-[F]Fluoro[dideutero]methoxyphenoxy)benzyl)morpholine ([F]FMeNER-D), 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 [F]bromofluoromethane-d using a fully automated F-labeling synthesizer with a two-pot unit. We simplified the automated radiosynthesis of [F]FMeNER-D through the use of a straightforward one-pot method to prepare [F]fluoromethyl-d-tosylate as the fluoromethylating agent (avoiding the need to azeotropically dry [F]F in advance), which was then reacted with NER. The reaction conditions were optimized, with [F]FMeNER-D synthesized using an F-labeling synthesizer equipped with a one-pot unit. As a result, a synthesis time, radiochemical yield based on total [F]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 [F]FMeNER-D using a simplified one-pot, fully automated, F-fluoromethylation method in an F-labeling synthesizer.

Radiolabeled alcohols have been investigated for their use in the measurement of cerebral blood flow for years. In particular, [C]butanol has been employed as a freely diffusible tracer with appreciable tissue retention and good solubility in both lipid and aqueous compartments. It is an appropriate radiotracer for the assessment of blood supply and for the comparative evaluation of substrate utilization with blood flow. Herein, we describe a no-carrier-added [C]butanol radiosynthesis using the GE FASTLab 2 to leverage the benefits of a cassette-based workflow, and we compare it to our legacy radiosynthesis using GE TracerLab FX modules. Using the FASTLab 2, [C]butanol was synthesized in 21 min with a radiochemical yield of 4%-8% (n = 3) and a radiochemical purity of > 90%. Synthesis on the FASTLab was fast, reliable, and comparable to syntheses using TracerLab FX modules.

In the present study, the influence of activated carbon (AC) on mineralization, degradation, extractable residues, and bound residue formation of C-sulfamethoxazole and C-acetaminophen was investigated. The results showed that AC facilitated the dissipation of C-sulfamethoxazole and C-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 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.

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-[F]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%.

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-C2]dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (C-ARV-110-a) and N-((1R,4R)-4-(3-chloro-4-[cyano-C]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 (C-ARV-110-b). The synthesis of C-ARV-110-a was initiated from 1,2-dibromo-4,5-difluorobenzene and zinc cyanide-C (Zn(CN)₂), while C-ARV-110-b was prepared from 2-chloro-4-fluoro[cyano-C]benzonitrile.

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 Tc-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 (Tc) using different reaction parameters. The Tc-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 Tc-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 Tc-labeled TCMC-RNB holds promise as a specific imaging agent for the diagnosis and monitoring of VEGF-related malignancies, particularly in NSCLC.

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 C-radiolabeled and stable-isotope labeled variants of deucravacitinib is described in this publication.

Three novel C-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-C 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-C 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-C and 5-MeO-DMT-2-C 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.