18F-FDG-PET/CT-based machine learning model evaluates indeterminate adrenal nodules in patients with extra-adrenal malignancies.

BACKGROUND: To assess the value of an 18F-FDG-positron emission tomography/computed tomography (PET/CT)-based machine learning model for distinguishing between adrenal benign nodules (ABNs) and adrenal metastases (AMs) in patients with indeterminate adrenal nodules and extra-adrenal malignancies. METHODS: A total of 303 patients who underwent 18F-FDG-PET/CT with indeterminate adrenal nodules and extra-adrenal malignancies from March 2015 to June 2021 were included in this retrospective study (training dataset (n = 182): AMs (n = 97), ABNs (n = 85); testing dataset (n = 121): AMs (n = 68), ABNs (n = 55)). The clinical and PET/CT imaging features of the two groups were analyzed. The predictive model and simplified scoring system for distinguishing between AMs and ABNs were built based on clinical and PET/CT risk factors using multivariable logistic regression in the training cohort. The performances of the predictive model and simplified scoring system in both the training and testing cohorts were evaluated by the areas under the receiver operating characteristic curves (AUCs) and calibration curves. The comparison of AUCs was evaluated by the DeLong test. RESULTS: The predictive model included four risk factors: sex, the ratio of the maximum standardized uptake value (SUVmax) of adrenal lesions to the mean liver standardized uptake value, the value on unenhanced CT (CTU), and the clinical stage of extra-adrenal malignancies. The model achieved an AUC of 0.936 with a specificity, sensitivity and accuracy of 0.918, 0.835, and 0.874 in the training dataset, respectively, while it yielded an AUC of 0.931 with a specificity, sensitivity, and accuracy of 1.00, 0.735, and 0.851 in the testing dataset, respectively. The simplified scoring system had comparable diagnostic value to the predictive model in both the training (AUC 0.938, sensitivity: 0.825, specificity 0.953, accuracy 0.885; P = 0.5733) and testing (AUC 0.931, sensitivity 0.735, specificity 1.000, accuracy 0.851; P = 1.00) datasets. CONCLUSIONS: Our study showed the potential ability of a machine learning model and a simplified scoring system based on clinical and 18F-FDG-PET/CT imaging features to predict AMs in patients with indeterminate adrenal nodules and extra-adrenal malignancies. The simplified scoring system is simple, convenient, and easy to popularize.

Base-Promoted Reactions of Organostibines with Alkynes and Organic Halides to Give Chalcogenated (Z)-Olefins and Ethers.

Herein, with air-stable chalcogenated stibines (Sb-ER) as organometallic chalcogenating reagents, we developed base-promoted (Z)-hydrochalcogenation of alkynes with DMSO/DMSO-d6 as hydrogen/deuterium sources, giving chalcogenated (Z)-olefins in good yields and with excellent regioselectivity. These reagents, easily synthesized from halostibines with in situ generated [Zn(ER)2] at room temperature within a few minutes, could be also used in the base-promoted C(sp3)-S(Se) cross-coupling with C(sp3)-X and copper-catalyzed C(sp2)-S(Se) cross-coupling with C(sp2)-X (X = F, CI, Br, I) under mild conditions. This protocol could also be simply extended to organobismuth complexes (Bi-ER) with good functional tolerance.

Pd-Catalyzed Cross-Coupling of Sb-Aryl Stibines with Halogenomethyl Arenes to Give Unsymmetirc Diarylmethanes.

Herein, we describe a general method for the synthesis of unsymmetric diarylmethanes from (hetero)aryl methyl halides and Sb-aryl stibines. This protocol shows a broad substrate scope and a good functional group tolerance. Drug molecules, including beclobrate 3al and bifemelane 3as, and drug derivatives, including celecoxib 3p, ibuprofen 3ao, and probenecid 3ap, were efficiently synthesized on a gram scale. The possible mechanism is proposed on the basis of the results of control experiments.

Pd-Catalyzed Cross-Coupling of Organostibines with Styrenes to Give Unsymmetric (E)-Stilbenes and (1E,3E)-1,4-Diarylbuta-1,3-dienes and Fluorescence Properties of the Products.

A general and effective palladium-catalyzed cross-coupling of organostibines with styrenes to give (E)-olefins was disclosed. By the use of an organostibine reagent, this method can produce unsymmetric (E)-1,2-diarylethylenes and (1E,3E)-1,4-diarylbuta-1,3-dienes in good yields with high E/Z selectivity and good functional group tolerance. Resveratrol and DMU-212 were synthesized in high yield. The protocol can be extended to the synthesis of (1E,3E,5E)-1,6-diphenylhexa-1,3,5-triene in 40% yield. Products 5e, 5f, and 7a showed good photoluminescence quantum yields ranging from 72 to 99%.

Nickel- and Palladium-Catalyzed Cross-Coupling Reactions of Organostibines with Organoboronic Acids.

A strategy for the formation of antimony-carbon bond was developed by nickel-catalyzed cross-coupling of halostibines. This method has been applied to the synthesis of various triaryl- and diarylalkylstibines from the corresponding cyclic and acyclic halostibines. This protocol showed a wide substrate scope (72 examples) and was compatible to a wide range of functional groups such as aldehyde, ketone, alkene, alkyne, haloarenes (F, Cl, Br, I), and heteroarenes. A successful synthesis of arylated stibine 3 a in a scale of 34.77 g demonstrates high synthetic potential of this transformation. The formed stibines (R3 Sb) were then used for the palladium-catalyzed carbon-carbon bond forming reaction with aryl boronic acids [R-B(OH)2 ], giving biaryls with high selectivity, even the structures of two organomoieties (R and R') are very similar. Plausible catalytic pathways were proposed based on control experiments.

Two novel cocrystals of lamotrigine with isomeric bipyridines and in situ monitoring of the cocrystallization.

Crystal engineering strategy was applied to develop new solid forms of lamotrigine. Two novel cocrystals of lamotrigine forming with 4,4'-bipyridine (2:1) and 2,2'-bipyridine cocrystal (1:1.5) were successfully obtained by neat grinding and liquid assisted grinding. The novel cocrystals were fully characterized and confirmed by X-ray diffraction, thermal and spectroscopic analysis. DXRxi Raman microscope was also used to identify the cocrystals. The factors such as solvent and the structure of coformers which influenced the cocrystal formation were discussed. Furthermore, the novel cocrystals were both obtained by slurry crystallization. Process analytical technologies including focused beam reflectance measurement and attenuated total reflectance Fourier Transform Infrared were applied to investigate the cocrystallization process and the mechanism. HPLC analysis showed that the dissolution rate and the solubility of the two novel cocrystals were both improved.