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The aim of this study is to synthesize I-labeled 2-(4-iodophenethyl)-2-methylmalonic acid ([I]IMA) for the development of new apoptosis imaging tracer. The optimized radiolabeling procedure provided [I]IMA with high radiochemical yield (75.5 ± 5.2 %) and radiochemical purity (>99 %) within 100 min. Specific radioactivity of [I]IMA was 31.0 MBq/μmol. Biodistribution study of [I]IMA was carried out using ICR mouse and the result showed the uptake values in apoptotic cells of the testes of the male mice were 1.7-3.2 fold higher than those of leg muscle. Therefore, [I]IMA will be a promising radiotracer for in vivo SPECT imaging of apoptotic cells. [ABSTRACT FROM AUTHOR]

Herein we report an efficient method for iodine radioisotope labeling of cyclooctyne-containing molecules using copper-free click reaction. For this study, radioiodination using the tin precursor 2 was carried out at room temperature to give 125 I-labeled azide ([ 125 I] 1 ) with high radiochemical yield (85%) and excellent radiochemical purity. Dibenzocyclooctyne (DBCO) containing cRGD peptide and gold nanoparticle were labeled with [ 125 I] 1 at 37 °C for 30 min to give triazoles with good radiochemical yields (67–95%). We next carried out tissue biodistribution study of [ 125 I] 1 in normal ICR mice to investigate the level of organ accumulation which needs to be considered for pre-targeted in vivo imaging. Large amount of [ 125 I] 1 distributed rapidly in liver and kidney from bloodstream and underwent rapid renal and hepatobiliary clearance. Moreover [ 125 I] 1 was found to be highly stable (>92%) in mouse serum for 24 h. Therefore [ 125 I] 1 could be used as a potentially useful radiotracer for pre-targeted imaging. Those results clearly indicated that the present radiolabeling method using copper free click reaction would be quite useful for both in vitro and in vivo labeling of DBCO group containing molecules with iodine radioisotopes. [ABSTRACT FROM AUTHOR]

Concern about environmental exposure to hazardous substances has grown over the past several decades, because these substances have adverse effects on human health. Methods used to monitor the biological uptake of hazardous substances and their spatiotemporal behavior in vivo must be accurate and reliable. Recent advances in radiolabeling chemistry and radioanalytical methodologies have facilitated the quantitative analysis of toxic substances, and whole-body imaging can be achieved using nuclear imaging instruments. Herein, we review recent literature on the radioanalytical methods used to study the biological distribution, changes in the uptake and accumulation of hazardous substances, including industrial chemicals, nanomaterials, and microorganisms. We begin with an overview of the radioisotopes used to prepare radiotracers for in vivo experiments. We then summarize the results of molecular imaging studies involving radiolabeled toxins and their quantitative assessment. We conclude the review with perspectives on the use of radioanalytical methods for future environmental research. [ABSTRACT FROM AUTHOR]

In recent years, several catalyst-free site-specific reactions have been investigated for the efficient conjugation of biomolecules, nanomaterials, and living cells. Representative functional group pairs for these reactions include the following: (1) azide and cyclooctyne for strain-promoted cycloaddition reaction, (2) tetrazine and trans-alkene for inverse-electron-demand-Diels–Alder reaction, and (3) electrophilic heterocycles and cysteine for rapid condensation/addition reaction. Due to their excellent specificities and high reaction rates, these conjugation methods have been utilized for the labeling of radioisotopes (e.g., radiohalogens, radiometals) to various target molecules. The radiolabeled products prepared by these methods have been applied to preclinical research, such as in vivo molecular imaging, pharmacokinetic studies, and radiation therapy of cancer cells. In this review, we explain the basics of these chemical reactions and introduce their recent applications in the field of radiopharmacy and chemical biology. In addition, we discuss the significance, current challenges, and prospects of using bioorthogonal conjugation reactions. [ABSTRACT FROM AUTHOR]

5-Chloro-2-methyl-4-isothiazolin-3-one (CMIT) and 2-methyl-4-isothiazolin-3-one (MIT) used as preservatives in various products, including humidifier disinfectants, presents substantial health hazards. This research delves into the toxicological assessments of CMIT/MIT in the respiratory system using animal models. Through the synthesis of radiolabeled [14C]CMIT and [14C]MIT, we investigated the biological uptake and in vivo behaviors of CMIT/MIT in the respiratory tissues following intratracheal exposure. Quantitative whole-body autoradiography (QWBA) revealed significant persistence of CMIT/MIT in lung tissue. In addition, radio high-performance liquid chromatography (radio-HPLC) with tandem mass spectrometry (LC-MS/MS) was employed for metabolite profiling and identification. Notably, around 28% of the radiolabel was retained in tissue after the extraction step, suggesting covalent binding of CMIT/MIT and their metabolites with pulmonary biomolecules. This observation demonstrates the propensity of the electrophilic isothiazolinone ring in CMIT/MIT to undergo chemical interactions with biothiols in proteins and enzymes, fostering irreversible alterations of biomolecules. Such accumulations of transformations could result in direct toxicity at both cellular and organ levels. Additionally, the detection of metabolites, including a MIT dimer conjugated with glutathione (GSH), as analyzed by mass spectrometry indicates the possible reduction of cellular GSH levels and subsequent oxidative stress. This investigation offers an in-depth insight into the toxic mechanisms of CMIT/MIT, underlying their capability to engage in complex formations with biomacromolecules and induce pronounced respiratory toxicity. These results highlight the imperative for stringent safety assessments of these chemicals, advocating for improved public health and safety measures in the use of chemicals. [Display omitted] • The radiolabeled CMIT and MIT were synthesized using radioactive carbon (14C). • The SUV of CMIT/MIT in lung was determined to be 6.01 after 0.083 h post exposure. • In the analysis of metabolites, the parent structures of CMIT/MIT were not observed. • Some metabolites were found to be conjugated with glutathione. • Approximately 28% of the radiolabel was bound to pulmonary biomolecules. [ABSTRACT FROM AUTHOR]

Benzylalkyldimethylammonium chloride (BAC), a quaternary ammonium compound (QAC), is utilized in industrial and biomedical applications for antimicrobial purposes. Since the coronavirus disease (COVID-19) outbreak, various types of BAC-containing household chemicals have been produced. BACs have several adverse effects; however, their biological uptake, translocation, and excretion in animal models (essential for better understanding in vivo behavior and toxicological impact) remain unclear. In this study, we performed the first biodistribution and whole-body imaging studies of BAC in male Sprague Dawley rats, using two different administration routes. Quantitative whole-body autoradiography (QWBA) data obtained for intranasal 14C-labeled BAC ([14C]C12-BAC) exposure showed substantial uptake values for the respiratory organs (e.g. 346 ng g−1 of lung at 3 h post administration) and the radiotracer was transported to other internal organs. The amount of radiotracer in the heart, adrenal gland, and pancreas were 198, 1410, and 186 ng g−1 tissue respectively at 168 h following exposure. Autoradiograms obtained after intravenous injection also showed high accumulation and slow excretion in these organs. The cumulative excretion analysis revealed that approximately 6.4% of the administered radioactivity remained in rats after a week. The results indicated that continuous inhalation exposure to BAC leads to potential toxic effects in extrapulmonary organs and the respiratory tract. Thus, the radiolabeling method utilized may help assess various synthetic QACs in living subjects. [Display omitted] • The radiolabeled benzylalkyldimethylammonium chloride (BAC) was synthesized. • Biological uptake and in vivo behavior of BAC were assessed using the radiotracer. • 14C-labeled BAC was administered in rats via the intranasal and intravenous routes. • After the inhalation exposure, BAC was translocated to extrapulmonary organs. • Significant accumulations were observed in the heart, adrenal gland, and pancreas. [ABSTRACT FROM AUTHOR]

[Display omitted] • The biodistribution of CMIT/MIT was assessed using a 14C-labeled radiotracer. • After exposure via the inhalation routes, CMIT/MIT is rapidly distributed to the lungs. • Intratracheal exposure induces greater lung damage than intranasal instillation. • The amount of CMIT/MIT in the lungs is positively associated with the toxicity. A variety of isothiazolinone-containing small molecules have been registered and used as chemical additives in many household products. However, their biodistribution and potential harmful effects on human health, especially respiratory effects, were not yet identified in sufficient detail. The purpose of this study was to investigate whether a biocide comprising a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) could reach the lungs and induce lung injury when exposure occurs by two administration routes involving the respiratory tract: intratracheal and intranasal instillation. To investigate the biodistribution of CMIT/MIT, we quantified the uptake of 14C-labeled CMIT/MIT in experimental animals for up to seven days after intratracheal and intranasal instillation. In the toxicity study, lung injury was assessed in mice using total inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung histopathology. The results of the biodistribution study indicated that CMIT/MIT were rapidly distributed throughout the respiratory tract. Using quantitative whole-body autoradiogram analysis, we confirmed that following intranasal exposure, CMIT/MIT reached the lungs via the respiratory tract (nose–trachea–lung). After 5 min post intratracheal and intranasal instillation, the amount of radiotracer ([14C]CMIT/MIT) in the lungs was 2720 ng g−1 and 752 ng g−1 tissue, respectively, and lung damage was observed. A higher amount of the radiotracer resulted in higher toxicity. Both intratracheal and intranasal instillation of CMIT/MIT increased inflammatory cell counts in the BALF and induced injuries in the alveoli. The frequency and the severity scores of injuries caused by intratracheal instillation were approximately-four to five times higher than those induced by intranasal instillation. Therefore, we concluded that CMIT/MIT could reach the lungs following nasal and intratracheal exposure and cause lung injuries, and the extent of injury was dependent on the exposure dose. [ABSTRACT FROM AUTHOR]