Journal of labelled compounds & radiopharmaceuticals最新文献

Carbon-14 labeling is fundamentally important for supporting the development of new agrochemicals and pharmaceuticals. Given its critical importance, continued innovation in technologies and methodologies for radiolabeling should be strongly encouraged to better support the radiochemistry community. However, a persistent gap often exists between technological breakthroughs and their broad adoption by the scientific community. To help bridge this gap, we have developed a Practitioner Protocol detailing a recent method from our laboratory. This protocol describes how to produce ¹⁴C-labeled carbon monoxide ([¹⁴C]CO) directly from the universal precursor, [¹⁴C]carbon dioxide ([¹⁴C]CO₂). We hope this protocol will facilitate the adoption and implementation of this technology in other radiochemistry laboratories, thereby enhancing radiolabeling capabilities across the field.

Florasulam is a triazolopyrimidine herbicide that controls broadleaf and grass weeds in cereal crops and turf. It acts as an acetolactase synthase (ALS) inhibitor, blocking the synthesis of essential amino acids required for plant growth. Due to its potency, florasulam is effective at very low application rates making it cost-effective with reduced environmental off-target effects. As is common practice, florasulam has been subject to periodic reviews by regulatory agencies during re-registration requirements since its introduction into the market in 1998. The goal of these reviews is to ensure that the herbicide carries out its intended use without creating adverse side effects to humans and the environment. Since scientific methods are continually evolving and being developed, global regulatory agencies can require additional studies to address data gaps for pesticide renewals. During this re-registration process for florasulam, new environmental fate studies were conducted to meet new European Food Safety Authority (EFSA) guidelines. Consequently, florasulam-[triazole(¹³C,¹⁵N₂)] and florasulam-[phenyl(¹³C₆)] stable isotopes were synthesized to support the re-registration process.

The use of medicinal plants as anti-cancer agents has attracted the attention of researchers. A method is needed for screening the anti-cancer effects on HER-2 receptors. In this study, a simple method based on radioligand binding studies was developed for primary screening of medicinal plants on HER-2 receptors in vitro. Trastuzumab was conjugated to HYNIC in a chemical reaction using NHS-HYNIC. HYNIC-Trastuzumab was radiolabeled with [99mTc] using SnCl₂ as a reducing agent and tricine as a coligand. Biological activities of [99mTc]Tc-HYNIC-Trastuzumab were determined in saturation binding studies using the SKBR3 cell line. The IC₅₀ of Mentha pulegium was determined in competition with [99mTc]Tc-HYNIC-Trastuzumab on the SKBR3 cell line. Radiochemical purity was ≥ 90% ± 2.08%. Based on the results, radiolabeled Trastuzumab maintained its biological activity after labeling (immunoreactivity = 83%, K_d = 7.049 ± 1.861 nM). The IC₅₀ of Mentha pulegium was 31.3 ± 1.3 μg/mL. [99mTc]Tc-HYNIC-Trastuzumab can be used as a radioligand in competition binding studies for primary screening of medicinal plants, peptides, and small molecules in vitro on HER-2 receptors.

[¹⁴C]2-Iminothiolane ([¹⁴C]2-IT) served as a highly informative analytical tool to determine the rate of lysine thiolation and total addition of 2-IT to a monoclonal antibody. Specific activity measurements on [¹⁴C]2-IT modified mAbs found that lysine thiolation with 2-IT is linear regarding time and dependent on buffer strength. Conjugation with a fluorescent maleimide directly linked the free thiol-to-antibody ratio (FTAR) to the [¹⁴C]2-IT-to-antibody ratio ([¹⁴C]ITAR), providing accurate predictive information on the true number of sites proficient for payload conjugation and, by comparison with conjugation with the cytotoxic payload, quantified the absorbance from the nonconjugated cyclized N-substituted 2-iminothiolane adduct that created “phantom” drug-to-antibody ratios (PhDAR). Hydrolytic loss of the nonconjugated cyclized N-substituted 2-iminothiolane adduct was investigated using carbon-14 based radioquantitative HPLC, mass spectral analysis, and orthogonal [¹⁴C]ITAR and DAR measurements of the isolated [¹⁴C]mAb. These measurements combined to demonstrate that significant amounts of the cyclized products were shed from the [¹⁴C]ADC as [¹⁴C]thiobutyrolactone.

Radiolabelled compound stability studies are an essential requirement to support human Absorption, Distribution, Metabolism and Excretion (hADME) clinical studies. This paper assesses the suitability of stability data extrapolation for carbon-14 labelled compounds following the principles set out in ICH Q1E guidelines. Data from seven stability studies at specific activities ranging from 8.2 to 81.0 μCi/mg have been assessed. Predictive models were employed to extrapolate stability data and determine extended retest periods, which were then subsequently verified against actual experimental results. In all cases, the predicted extended retest period aligned with the observed data. These findings demonstrate that stability extrapolations can be used to support extended retest periods for radiolabelled compounds.

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.