Increased Prostate-Specific Membrane Antigen Uptake in a Gallbladder Stone.

ABSTRACT: An Al 18F-prostate-specific membrane antigen (PSMA) Q PET/CT scan was performed in a 67-year-old man to identify any potential recurrent prostate cancer lesions, which revealed no recurrent or metastatic lesions. However, a large gallbladder stone with increased PSMA uptake was incidentally detected, which could be a potential pitfall in the interpretation of PSMA PET imaging.

Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy.

Background: Radiotherapy (RT) may trigger systemic antitumor immunity, manifesting as regression of non-irradiated lesions (abscopal effect). Intracellular adhesion molecule-1 (ICAM-1) is a key molecule involved in the abscopal effect of RT. However, the specific function of ICAM-1 in CD8+ T cells during antitumor immune responses remains unclear. Herein, we investigated whether noninvasive imaging of ICAM-1 can be used to annotate CD8+ T-cell function, thereby better selecting combinational therapy to enhance the antitumor immunity induced by RT. Methods: Using knockout mouse models, we investigated the role of ICAM-1 expressed on CD8+ T cells in the antitumor immunity of RT and conducted drug screening guided by ICAM-1-targeted noninvasive imaging. Results: The systemic antitumor effect of RT relies on the expression of ICAM-1 on CD8+ T cells. ICAM-1 expression is essential for CD8+ T-cell activation, proliferation, and effector function. Noninvasive annotation of the proliferation and effector function of CD8+ T cells by ICAM-1-targeted imaging identified VS-6063, a focal adhesion kinase inhibitor, as a new adjuvant to augment systemic antitumor immunity of RT in an immunologically "cold" tumor model. Mechanistically, VS-6063 overcomes the physical barriers in tumors and promotes the migration and infiltration of CD8+ T cells primed by RT into distant tumors. Conclusion: Our findings highlight that molecular imaging of ICAM-1 levels provides a dynamic readout of the proliferation and effector function of tumor-infiltrating CD8+ T cells, which facilitates the high-throughput exploitation of new combinational drugs to maximize the systemic antitumor effect of RT.

Comparison of 18 F-FDG and 18 F-FAPI PET/CT Findings of Signet-Ring Cell Carcinoma of the Stomach.

ABSTRACT: A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.

A one-pot approach to prepare stretchable and conductive regenerated silk fibroin/CNT films as multifunctional sensors.

Silk fibroin (SF)-based materials are characterized by their outstanding biocompatibility and biodegradability and are considered as the most promising candidates for next-generation flexible electronics. In order to generate such devices, SF can be mixed with carbon nanotubes (CNTs) which feature excellent mechanical, electrical, and thermal properties. However, obtaining regenerated SF with homogeneous dispersion of CNTs in a sustainable manner represents a challenging task, mainly due to the difficulty in overcoming van der Waals forces and strong π-π interactions that hold together the CNT structure. In this study, a one-pot strategy for fabricating SF/CNT films is proposed by designing SF as a modifier of CNTs through non-covalent interactions with the assistance of aqueous phosphoric acid solution. Glycerol (GL) was introduced, endowing the SF/GL/CNT composite film with excellent flexibility and stretchability. The sustainable strategy greatly simplifies the preparation process, avoiding dialysis of SF and the use of artificial dispersants. The as-fabricated SF/GL/CNT films showed an excellent mechanical strength of 1.20 MPa and high sensitivity with a gauge factor of up to 13.7 toward tensile deformation. The composite films had a sensitive monitoring capability for small strains with detection limits as low as 1% and can be assembled into versatile sensors to detect human movement. Simultaneously, the composite films showed a superb thermosensitive capacity (1.64% °C-1), which satisfied the requirement of real-time and continuous skin temperature monitoring. We anticipate that the presented one-pot strategy and the prepared composite films could open a new avenue for forthcoming technologies for electronic skins, personal health monitoring, and wearable electronics.

Conformational enantiodiscrimination for asymmetric construction of atropisomers.

Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1'-bi-2-naphthol (BINOL) unit which are connected via a C-O single bond. The two conformers of the catalyst induced by the rotation about the C-O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1'-binaphthyl-2,2'-diamine (BINAM) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.

Multi-lesion radiomics of PET/CT for non-invasive survival stratification and histologic tumor risk profiling in patients with lung adenocarcinoma.

OBJECTIVES: This study investigates the ability of machine learning (ML) models trained on clinical data and 2-deoxy-2-[18F]fluoro-D-glucose(FDG) positron emission tomography/computed tomography (PET/CT) radiomics to predict overall survival (OS), tumor grade (TG), and histologic growth pattern risk (GPR) in lung adenocarcinoma (LUAD) patients. METHODS: A total of 421 treatment-naive patients with histologically-proven LUAD and available FDG PET/CT imaging were retrospectively included. Four cohorts were assessed for predicting 4-year OS (n = 276), 3-year OS (n = 280), TG (n = 298), and GPR (n = 265). FDG-avid lesions were delineated, and 2082 radiomics features were extracted and combined with endpoint-specific clinical parameters. ML models were built for the prediction of 4-year OS (M4OS), 3-year OS (M3OS), tumor grading (MTG), and histologic growth pattern risk (MGPR). A 100-fold Monte Carlo cross-validation with 80:20 training to validation split was employed as a performance evaluation for all models. The association between the M4OS and M3OS predictions with OS was assessed by the Kaplan-Meier survival analysis. RESULTS: The area under the receiver operator characteristics curve (AUC) was the highest for M4OS (AUC 0.88, 95% confidence interval (CI) 86.7-88.7), followed by M3OS (AUC 0.84, CI 82.9-84.9), while MTG and MGPR performed equally well (AUC 0.76, CI 74.4-77.9, CI 74.6-78, respectively). Predictions of M4OS (hazard ratio (HR) -2.4, CI -2.47 to -1.64, p < 0.05) and M3OS (HR -2.36, CI -2.79 to -1.93, p < 0.05) were independently associated with OS. CONCLUSION: ML models are able to predict long-term survival outcomes in LUAD patients with high accuracy. Furthermore, histologic grade and predominant growth pattern risk can be predicted with satisfactory accuracy. KEY POINTS: • Machine learning models trained on pre-therapeutic PET/CT radiomics enable highly accurate long-term survival prediction of patients with lung adenocarcinoma. • Highly accurate survival predictions are achieved in lung adenocarcinoma patients despite heterogenous histologies and treatment regimens. • Radiomic machine learning models are able to predict lung adenocarcinoma tumor grade and histologic growth pattern risk with satisfactory accuracy.

Solitary Periaortic Tuberculous Granuloma Mimicking Neoplastic Disease on 18 F-FDG PET/CT.

ABSTRACT: Solitary tuberculoma of periaortic space is extremely rare. We report a case of periaortic tuberculous granuloma revealed by 18 F-FDG PET/CT in a 51-year-old woman without pulmonary or any other organ involvement. Awareness of this rare but possible atypical presentation of tuberculosis is helpful for the differential diagnosis of periaortic mass.

Antibacterial thyme oil-loaded zwitterionic emulsion hydrogels.

Emulsion hydrogels are structurally composite materials combining the advantages of emulsions and hydrogels with the ability to accommodate hydrophobic and hydrophilic components in one system. It is a promising strategy for the excellent encapsulation and delivery of many bioactive ingredients. In this work, the thyme oil-loaded zwitterionic emulsion hydrogels are constructed by the cellulose acetoacetate-horseradish peroxidase-hydrogen peroxide-initiated (CAA-HRP-H2O2-initiated) ternary enzyme-mediated polymerization of the thyme oil-in-water (O/W) emulsions stabilized by cellulose acetoacetate (CAA). CAA is the key component in the system, acting as the emulsifier and the polymerization mediator simultaneously. The formed zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogel network provides emulsion hydrogels with good hydration capacity and potential anti-fouling performance. The thyme oil-loaded zwitterionic emulsion hydrogels exhibit interconnected, uniform, and adjustable porous structures with tunable mechanical properties, antifouling performance, good biocompatibility, and excellent antibacterial activity against S. aureus and E. coli. These results all demonstrate that the ternary enzyme-mediated polymerization of zwitterionic monomers in the continuous phase of O/W emulsion templates is a facile and efficient strategy to encapsulate hydrophobic bioactive ingredients.

Verification of Duodenobiliary Reflux With SPECT/CT Imaging.

ABSTRACT: Duodenobiliary reflux is believed to be 1 of the causes of recurrent bacterial cholangitis. We reported a 65-year-old woman with intermittent epigastric pain for 20 years. She was diagnosed with cholelithiasis in the past, and she still had recurrent abdominal pain after the stone was removed. The patient was suspected of having duodenobiliary reflux and received duodenobiliary reflux imaging. After oral administration of 700 mL water containing 5 mCi 99mTc-DTPA, SPECT/CT images of the abdomen were acquired. Abnormal radioactivity was seen in the common bile duct, indicating the presence of duodenobiliary reflux.

Organocatalytic asymmetric formal [3 + 2] cycloaddition reaction of isocyanoacetates with saccharin-derived 1-azadienes.

An efficient organocatalytic diastereo- and enantioselective formal [3 + 2] cycloaddition reaction of α-isocyanoacetates with saccharin-derived 1-azadienes catalyzed by a dihydroquinine derived squaramide catalyst has been investigated, and it furnished the corresponding directly linked benzo[d]isothiazole 1,1-dioxide-dihydropyrroles with two adjacent tertiary-quaternary stereocenters in high yields (up to 98%), with moderate to excellent stereoselectivities (up to >20 : 1 dr and 97% ee) under mild conditions.

Asymmetric synthesis of dihydrocoumarins via catalytic sequential 1,6-addition/transesterification of α-isocyanoacetates with para-quinone methides.

A catalytic asymmetric synthesis of 3,4-dihydrocoumarins with adjacent tertiary-quaternary stereocenters by 1,6-addition/transesterification cascade reaction of α-isocyanoacetates with ortho-hydroxyphenyl-substituted para-quinone methides (p-QMs) has been developed. Using a combination of dihydroquinidine-derived aminophosphine and silver nitrate as a binary catalytic system, moderate to good yields, excellent diastereoselectivities (>20 : 1 dr) and good to excellent enantioselectivities (up to 94% ee) were achieved for a wide range of isocyanoacetates and p-QMs.

Cinchona Alkaloid Squaramide-Catalyzed Asymmetric Ugi-Type Reaction of Isocyanoacetates with C,N-Cyclic Azomethine Imines: Access to Chiral Oxazole-Substituted Tetrahydroisoquinolines.

We reported herein an unexpected cinchona alkaloid-derived squaramide-catalyzed asymmetric two-component Ugi-type reaction of α-aryl-substituted isocyanoacetates with C,N-cyclic azomethine imines, which provides concise access to optically active C1-oxazole-substituted tetrahydroisoquinolines in good yields (86-93%) and high enantioselectivities (up to 98% enantiomeric excess) under mild conditions.

A better prediction of progression-free survival in diffuse large B-cell lymphoma by a prognostic model consisting of baseline TLG and %ΔSUVmax.

In the era of rituximab, the International Prognostic Index (IPI) has been inefficient in initial risk stratification for patients with R-CHOP-treated diffuse large B-cell lymphoma (DLBCL). To estimate the predictive values of PET/CT quantitative parameters and three prognostic models consisting of baseline and interim parameters for three-year progression-free survival (PFS), we conducted an analysis of 85 patients in China with DLBCL underwent baseline and interim PET/CT scans and treated at the Department of Hematology of Peking University Third Hospital from November 2012 to November 2017. The PET/CT parameters, viz. the baseline and interim values of standardized uptake value (SUVmax ), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), and their rates of change, were analyzed by a receiver operating characteristics curve, Kaplan-Meier analysis, and log-rank test. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was also included in the multivariate Cox hazards model. Owing to the strong correlation between TMTV and TLG at baseline and interim (Pearson's correlation coefficient, r = 0.823, P-value = 0.000, and 0.988, P-value = 0.000, respectively), only TLG was included in the multivariate Cox hazards model, where TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% showed predictive value independently (HR = 10.42, 95% CI 2.35-46.30, P = 0.002, and HR = 4.86, 95% CI 1.27-18.54, P = 0.021, respectively). Replacing TLG in the equation, TMTV0 and TMTV1 both showed significantly predictive abilities like TLG (HR = 8.22, 95% CI 1.86-32.24, P = 0.005, and HR = 2.96, 95% CI 1.16-7.54, P = 0.023, respectively). After dichotomy, NCCN-IPI also gave a significant performance (P = 0.035 and P = 0.010, respectively, in TLG and TMTV models). The baseline variables, that is, TMTV0 , TLG0 and dichotomized NCCN-IPI, and the interim variables TMTV1 and %ΔSUVmax , presented independent prognostic value for PFS. In prognostic model 2 (TLG0  + %ΔSUVmax ), the group with TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% recognized 19 (82.6%) of the relapse or progression events, which showed the best screening ability among three models consisting of baseline and interim PET/CT parameters.

Early detection value of 18F-FDG-PET/CT for drug-induced lung injury in lymphoma.

Recent studies have not only shown better prognosis of lymphoma with the advancement of therapeutic drug development, but also suggested more attention should be paid to drug-induced lung injury. Early diagnosis is critical for treatment of drug-induced lung injury. 18F-FDG-PET/CT, the standard imaging method for prognosis evaluation of Hodgkin's lymphoma and some non-Hodgkin's lymphoma, has also shown the potential for early detection of drug-induced lung injury in our study. A total of 579 lymphoma patients evaluated by 18F-FDG-PET/CT between June 2016 and March 2018 are studied retrospectively. Clinical and imaging characteristics are described in 32 patients (average age of 55), who were diagnosed with drug-induced lung injury. The incidence of drug-induced lung injury was 5.53% (32/579); most of the chemotherapy regimens include rituximab (90.63%, 29/32). Twelve patients demonstrated fever, cough, and dyspnea, and the other 20 had no significant symptoms. 18F-FDG-PET/CT showed multiple or diffused distribution of ground glass and patchy shadows, with increased FDG uptake in both lungs (SUVmax 2.28 ± 1.13, standardized uptake ratio-blood pool, SUR-BP = 0.59-4.07, median SUR-BP 1.32). SUVmax and SUR-BP in patients with symptoms (SUVmax 3.03 ± 1.33 and SUR-BP 2.12 ± 1.06) were significantly higher than in those without symptoms (SUVmax 1.84 ± 0.70 and SUR-BP 1.18 ± 0.48) (P = 0.002 for both SUVmax and SUR-BP). After temporary drug withdrawal, changing chemotherapy regimens, and corticosteroid usage, the pulmonary lesions in all patients were relieved, confirmed with chest CT. Drug-induced lung injury can be a co-finding during 18F-FDG-PET/CT assessment of lymphoma. With positive correlation between FDG uptake and symptoms, 18F-FDG-PET/CT provided value in early detection of lung injury in asymptomatic patients.

Organocatalyzed asymmetric tandem conjugate addition-protonation of isocyanoacetates to 2-chloroacrylonitrile.

An efficient organocatalytic asymmetric tandem conjugate addition-protonation of α-substituted isocyanoacetates to 2-chloroacrylonitrile catalyzed by dihydroquinine-derived thiourea has been investigated, affording the corresponding adducts with two non-adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) along with good to excellent diastereo- and enantioselectivities (up to 20 : 1 dr, up to 95% ee) under mild conditions. The adduct can also be transformed into chiral γ-lactam by synthetic transformations.

Diastereo- and enantioselective Mannich/cyclization cascade reaction of isocyanoacetates with cyclic sulfamide ketimines by cinchona alkaloid squaramide/AgOAc cooperative catalysis.

We have developed an efficient diastereo- and enantioselective Mannich/cyclization cascade reaction of α-substituted isocyanoacetates with 4-aryl-3-carbonyl-1,2,5-thiadiazole-1,1-dioxide type cyclic sulfamide ketimines cooperatively catalyzed by cinchona alkaloid-derived squaramide and AgOAc. The corresponding optically active 2,3,3a,4-tetrahydroimidazo[1,5-b][1,2,5]thiadiazole-1,1-dioxide derivatives were obtained in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >20 : 1 dr, up to 94% ee).

Focally Increased FDG Activity in the Liver Related to Hydropic Degeneration.

A 50-year-old man, who had diffuse large B-cell lymphoma in the neck and just finished 4 cycles of chemotherapy, presented to our department to evaluate the status of the disease. FDG PET/CT revealed a focally increased activity in the right lobe of the liver. However, pathological examination showed hepatocyte hydropic degeneration with associated inflammatory cells without evidence of malignancy.

Cinchona Alkaloid Squaramide-Catalyzed Asymmetric Michael Addition of α-Aryl Isocyanoacetates to ß-Trifluoromethylated Enones and Its Applications in the Synthesis of Chiral ß-Trifluoromethylated Pyrrolines.

Cinchona alkaloid squaramide can effectively catalyze the asymmetric Michael addition of α-aryl isocyanoacetates to ß-trifluoromethylated enones, affording the corresponding adducts with an adjacent chiral tertiary carbon center bearing a CF3 group and a quaternary carbon center in moderate to good yields along with excellent stereoselectivities. The adduct can be easily transformed into biologically attractive chiral ß-trifluoromethylated pyrroline carboxylate in high yield via an isocyano group hydrolysis/cyclization/dehydration cascade reaction by treating with acid. The one-pot enantioselective Michael addition/isocyano group hydrolysis/cyclization/dehydration sequential protocol has also been investigated.

Cinchona alkaloid squaramide/AgOAc cooperatively catalyzed diastereo- and enantioselective Mannich/cyclization cascade reaction of isocyanoacetates and cyclic trifluoromethyl ketimines.

An efficient diastereo- and enantioselective Mannich-type/cyclization cascade reaction of α-substituted isocyanoacetates and cyclic trifluoromethyl ketimines cooperatively catalyzed by cinchona alkaloid-derived multi-hydrogen-bonding donor squaramide and AgOAc has been investigated, affording the optically active trifluoromethyl-substituted tetrahydroimidazo[1,5-c]quinazoline derivatives in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >15:1 dr, up to 98% ee) under mild conditions.

Cinchona alkaloid squaramide catalyzed enantioselective hydrazination/cyclization cascade reaction of α-isocyanoacetates and azodicarboxylates: synthesis of optically active 1,2,4-triazolines.

An efficient enantioselective hydrazination/cyclization cascade reaction of α-substituted isocyanoacetates to azodicarboxylates catalyzed by Cinchona alkaloid derived squaramide catalysts has been investigated, affording the optically active 1,2,4-triazolines in excellent yields (up to 99%) and good to excellent enantioselectivities (up to 97% ee) under mild conditions.