Journal of labelled compounds & radiopharmaceuticals最新文献

Radiolabeled aptamers are promising molecular probes for bioimaging because of their potential for high specificity, stability, and rapid clearance from nontarget tissues. They are single-stranded oligonucleotides labeled with radionuclides such as technetium-99m (⁹⁹ᵐTc), fluorine-18 (¹⁸F), and gallium-68 (⁶⁸Ga) to enable precise imaging via single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The versatility of radiolabeling strategies can provide opportunities to enhance biostability and pharmacokinetics while improving imaging sensitivity. In cancer theranostics, radiolabeled aptamers can allow early detection and treatment as well as facilitate effective monitoring of therapeutic responses. The applications of radiolabeled aptamers extend to infectious disease imaging, enabling real-time tracking of infections. Despite these advances, challenges such as rapid renal clearance, immunogenicity, and the need for clinical validation persist, catalyzing further research focused on enhancing the stability of radiolabeled aptamers, improving radiolabeling efficacy, and optimizing biodistribution. Emerging strategies, including nanoparticle conjugation and hybrid bioimaging, offer a great perspective for advancing the field. This article highlights recent advancements in radiolabeled aptamers in terms of their development, bioimaging applications, and research directions to address their limitations.

Synthesis of the key building block, 2-thiophenemethanamine-²H₅ hydrochloride, was achieved using mild conditions and purification methods in three steps from commercially available thiophene-²H₄, with an overall yield of 61.6% and an overall isotopic enrichment of 87.6%. 2-thiophenemethanamine-²H₅ hydrochloride has the potential to be a useful intermediate in the synthesis of isotopically labelled compounds of pharmaceutical interest.

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.

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.