Application of Dynamic [18F]FDG PET/CT Multiparametric Imaging Leads to an Improved Differentiation of Benign and Malignant Lung Lesions.

PURPOSE: To evaluate the potential of whole-body dynamic (WBD) 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) multiparametric imaging in the differential diagnosis between benign and malignant lung lesions. PROCEDURES: We retrospectively analyzed WBD PET/CT scans from patients with lung lesions performed between April 2020 and March 2023. Multiparametric images including standardized uptake value (SUV), metabolic rate (MRFDG) and distribution volume (DVFDG) were visually interpreted and compared. We adopted SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for semi-quantitative analysis, MRmax and DVmax values for quantitative analysis. We also collected the patients' clinical characteristics. The variables above with P-value < 0.05 in the univariate analysis were entered into a multivariate logistic regression. The statistically significant metrics were plotted on receiver-operating characteristic (ROC) curves. RESULTS: A total of 60 patients were included for data evaluation. We found that most malignant lesions showed high uptake on MRFDG and SUV images, and low or absent uptake on DVFDG images, while benign lesions showed low uptake on MRFDG images and high uptake on DVFDG images. Most malignant lesions showed a characteristic pattern of gradually increasing FDG uptake, whereas benign lesions presented an initial rise with rapid fall, then kept stable at a low level. The AUC values of MRmax and SUVmax are 0.874 (95% CI: 0.763-0.946) and 0.792 (95% CI: 0.667-0.886), respectively. DeLong's test showed the difference between the areas is statistically significant (P < 0.001). CONCLUSIONS: Our study demonstrated that dynamic [18F]FDG PET/CT imaging based on the Patlak analysis was a more accurate method of distinguishing malignancies from benign lesions than conventional static PET/CT scans.

Characteristics of whole-body dynamic 18F-FDG PET/CT Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters.

Background: Dynamic course of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak muti-parametric imaging spatial distribution in the targeted tissues may reveal highly useful clinical information about the tissue's metabolic properties. The characteristics of the Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters may provide reference for the clinical application of this new technology. Methods: A total of 27 patients with pathologically diagnosed lung cancer underwent whole-body dynamic 18F-FDG PET/CT examination before treatment. Parametric images of metabolic rate of FDG (MRFDG) and Patlak intercept (or distribution volume; DV) were generated using Patlak reconstruction. The values of primary lung cancer lesions, target-to-background ratio (TBR), and contrast-to-noise ratio (CNR) were investigated using contour delineation and boundary delineation. Statistical analysis was performed to analyze the relationship between multi-parametric images and clinicopathological features, and to compare the effects of contour delineation and boundary delineation on quantitative parameters. Results: MRFDG images showed higher TBR and CNR than did standardized uptake value (SUV) images. There were significant differences in MRFDG-max, MRFDG-mean, and MRFDG-peak among groups with different tumor diameters and pathology types (P<0.05). Moreover, the metabolic parameters of MRFDG were higher in patients with tumor diameters ≥3 cm and squamous carcinoma. The differences of the maximum and peak values of MRFDG and DV were not statistically significant in the different outlining method subgroups (all P>0.05). However, the difference of the mean values of MRFDG and DV were statistically significant in the different outline method groupings (all P<0.05). Conclusions: Dynamic 18F-FDG PET/CT Patlak multi-parametric imaging can obtain quantitative values for lung cancer with high TBR and CNR. Moreover, the multi-parameters are various from different pathology types to tumor size. Different delineation methods have a greater influence on the mean value of quantitative parameters.

Prognostic value of whole-body dynamic 18F-FDG PET/CT Patlak in diffuse large B-cell lymphoma.

Objective: This study aims to investigate the significance of interim whole-body dynamic 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak parameters for predicting the prognosis of patients with diffuse large B-cell lymphoma. To estimate the predictive value of the whole-body dynamic 18F-FDG PET/CT Patlak parameter for 2-year progression-free survival (PFS) and 2-year overall survival (OS). Methods: This study reports the findings of 67 patients with diffuse large B-cell lymphoma (DLBCL). These patients underwent interim whole-body dynamic 18F-FDG PET/CT scans from June 2021 to January 2023 at the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University. The predictive values of maximum standard uptake value (SUVmax), maximum of net glucose uptake rate (Kimax) and the predictive model combining Kimax and interim treatment response on the prognosis of patients was analyzed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival curves and log-rank tests were used for survival analysis. Univariate and multivariate analyses were performed to screen for independent prognostic risk factors. Results: After a median follow-up of 18 months, 21 patients (31.3%) experienced disease recurrence or death. The cut-off values for the SUVmax and the Kimax were 6.1 and 0.13 µmol min-1·ml-1, respectively. Ann Arbor stage, IPI, SUVmax, Kimax and interim treatment response were associated with PFS and OS in the univariate analysis. However, only Kimax and interim treatment response were independent influences on PFS and OS in multivariate analysis. Conclusion: Interim whole-body dynamic 18F-FDG PET/CT Patlak imaging has significant prognostic value in patients with DLBCL. Among them, the interim dynamic parameter Kimax showed the best predictive value for prognosis compared with the interim SUVmax and interim treatment response. The predictive model established by Kimax and the interim treatment response allowed for the accurate stratification of the prognostic risk of DLBCL.

Improved Clinical Workflow for Whole-Body Patlak Parametric Imaging Using Two Short Dynamic Acquisitions.

Objective: We sought to explore the feasibility of shorter acquisition times using two short dynamic scans for a multiparametric PET study and the influence of quantitative performance in shortened dynamic PET. Methods: Twenty-one patients underwent whole-body dynamic 18F-FDG PET/CT examinations on a PET/CT (Siemens Biograph Vision) with a total scan time of 75 min using continuous bed motion for Patlak multiparametric imaging. Two sets of Patlak multiparametric images were produced: the standard MRFDG and DVFDG images (MRFDG-std and DVFDG-std) and two short dynamic MRFDG and DVFDG images (MRFDG-tsd and DVFDG-tsd), which were generated by a 0-75 min post injection (p.i.) dynamic PET series and a 0-6 min + 60-75 min p.i. dynamic PET series, respectively. The maximum, mean, and peak values of the standard and two short dynamic multiparametric acquisitions were obtained and compared using Passing-Bablok regression and Bland-Altman analysis. Results: High correlations were obtained between MRFDG-tsd and MRFDG-std, and between DVFDG-tsd and DVFDG-std for both normal organs and all lesions (0.962 ≦ Spearman's rho ≦ 0.982, p < 0.0001). The maximum, mean, and peak values of the standard and two short dynamic multiparametric acquisitions were also in agreement. For normal organs, the Bland-Altman plot showed that the mean bias of MRFDG-max, MRFDG-mean, and MRFDG-peak was -0.002 (95% CI: -0.032-0.027), -0.002 (95% CI: -0.026-0.023), and -0.002 (95% CI: -0.026-0.022), respectively. The mean bias of DVFDG-max, DVFDG-mean, and DVFDG-peak was -3.3 (95% CI: -24.8-18.2), -1.4 (95% CI: -12.1-9.2), and -2.3 (95% CI: -15-10.4), respectively. For lesions, the Bland-Altman plot showed that the mean bias of MRFDG-max, MRFDG-mean, and MRFDG-peak was -0.009 (95% CI: -0.056-0.038), -0.004 (95% CI: -0.039-0.031), and -0.004 (95% CI: -0.036-0.028), respectively. The mean bias of DVFDG-max, DVFDG-mean, and DVFDG-peak was -8.4 (95% CI: -42.6-25.9), -4.8 (95% CI: -20.2-10.6), and -4.0 (95% CI: -23.7-15.6), respectively. Conclusions: This study demonstrates the feasibility of using two short dynamic scans that include the first 0-6 min and 60-75 min scans p.i. for Patlak multiparametric images, which can increase patient throughout for parametric analysis.

Photoinduced Arylation of Acridinium Salts: Tunable Photoredox Catalysts for C-O Bond Cleavage.

A photoinduced arylation of N-substituted acridinium salts has been developed and has exhibited a high functional group tolerance (e.g., halogen, nitrile, ketone, ester, and nitro). A broad range of well-decorated C9-arylated acridinium-based catalysts with fine-tuned photophysical and photochemical properties, namely, excited-state lifetimes and redox potentials have been synthetized in a one-step procedure. These functionalized acridinium salts were later evaluated in the photoredox-catalyzed fragmentation of 1,2-diol derivatives (lignin models). Among them, 2-bromophenyl substituted N-methyl acridinium has outperformed all photoredox catalysts, including commercial Fukuzumi's catalyst, for the selective CßO-Ar bond cleavage of diol monoarylethers to afford 1,2-diols in good yields.

Application of Nucleic Acid Frameworks in the Construction of Nanostructures and Cascade Biocatalysts: Recent Progress and Perspective.

Nucleic acids underlie the storage and retrieval of genetic information literally in all living organisms, and also provide us excellent materials for making artificial nanostructures and scaffolds for constructing multi-enzyme systems with outstanding performance in catalyzing various cascade reactions, due to their highly diverse and yet controllable structures, which are well determined by their sequences. The introduction of unnatural moieties into nucleic acids dramatically increased the diversity of sequences, structures, and properties of the nucleic acids, which undoubtedly expanded the toolbox for making nanomaterials and scaffolds of multi-enzyme systems. In this article, we first introduce the molecular structures and properties of nucleic acids and their unnatural derivatives. Then we summarized representative artificial nanomaterials made of nucleic acids, as well as their properties, functions, and application. We next review recent progress on constructing multi-enzyme systems with nucleic acid structures as scaffolds for cascade biocatalyst. Finally, we discuss the future direction of applying nucleic acid frameworks in the construction of nanomaterials and multi-enzyme molecular machines, with the potential contribution that unnatural nucleic acids may make to this field highlighted.

Urease: a highly efficient biocatalyst for synthesis of polyhydroquinolines and polyhydroacridines from the ammonia formed in situ.

Urease, a nickel-dependent enzyme, has a powerful catalytic activity to decompose urea into ammonia via hydrolysis reaction under mild condition. In the present work, urease was employed for the synthesis of two series of polyhydroquinoline and polyhydroacridine derivatives via one-pot condensation of the ammonia generated in situ from urea, aryl aldehydes, and dimedone or ethyl acetoacetate (i.e., Hantzsch-type reaction) in water under mild green condition. The valuable features of this enzymatic method are mild reaction conditions, short reaction times, wide substrate toleration, and high yield of products. The present work provides a novel enzymatic catalysis to synthesize polyhydroquinolines and polyhydroacridines and expands the application of urease in organic synthesis.

Synchronized independent narrow-band single photons and efficient generation of photonic entanglement.

We create independent, synchronized single-photon sources with built-in quantum memory based on two remote cold atomic ensembles. The synchronized single photons are used to demonstrate efficient generation of entanglement. The resulting entangled photon pairs violate a Bell's inequality by 5 standard deviations. Our synchronized single photons with their long coherence time of 25 ns and the efficient creation of entanglement serve as an ideal building block for scalable linear optical quantum information processing.

Reversal of mdrl gene-dependent multidrug resistance in multidrug resistance human leukemia cell line K562/ADM using short hairpin RNA expression vectors / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the role of reversal multidrug resistance (MDR) using short hairpin RNA (shRNA) expression vectors in multidrug resistance human leukemia cell line K562/ADM.</p><p><b>METHODS</b>The oligonucleotides with 19-mer hairpin structure were synthesized. The shRNA expression vectors were constructed and introduced into K562/ADM cells. Expression of mdr1 mRNA was assessed by RT-PCR, and P-gp expression was determined by Western blot. The apoptosis and sensitivity of the K562/ADM cells to doxorubicin were quantified by flow cytometry and methyl thiazolyl tetrazolium (MTT) assays, respectively. Cellular daunorubicin accumulation was assayed by laser confocal scanning microscope (LCSM).</p><p><b>RESULTS</b>In positive clones of K562/ADM cells stably transfected with pSilencer 3.1-HI neo mdr1-A and mdr1-B shRNA expression vectors, RT-PCR showed that mdr1 mRNA expression was significantly reduced to 35.9% (P < 0.05), 27.5% (P < 0.01), respectively. Western blot showed that P-gp expression was significantly and specifically inhibited. Resistance against doxorubicin was decreased from 79-fold to 38-fold (P < 0.05), 30-fold (P < 0.01) respectively. Furthermore, the fluorescence intensity of K562/ADM cells was increased significantly compared with the control. shRNA vectors significantly enhanced the cellular daunorubicin accumulation. The percent of the apoptosis cell was significantly enhanced to 18.1% (P < 0.05) , 54.4% (P < 0.01) respectively.</p><p><b>CONCLUSIONS</b>shRNA expression vectors can effectively reverse MDR, and restore the sensitivity of drug-resistance K562/ADM cells to conventional chemotherapeutic agents.</p>

Reversal of MDR1 gene-dependent multidrug resistance using short hairpin RNA expression vectors / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>RNA interference using short hairpin RNA (shRNA) can mediate sequence-specific inhibition of gene expression in mammalian cells. A vector-based approach for synthesizing shRNA has been developed recently. Overexpression of P-glycoprotein (P-gp), the MDR1 gene product, confers multidrug resistance (MDR) to cancer cells. In this study, we reversed MDR using shRNA expression vectors in a multidrug-resistant human breast cancer cell line (MCF-7/AdrR).</p><p><b>METHODS</b>The two shRNA expression vectors were constructed and introduced into MCF-7/AdrR cells. Expression of MDR1 mRNA was assessed by RT-PCR, and P-gp expression was determined by Western Blot and immunocytochemistry. Apoptosis and sensitization of the breast cancer cells to doxorubicin were quantified by flow cytometry and methyl thiazolyl tetrazolium (MTT) assays, respectively. Cellular daunorubicin accumulation was assayed by laser confocal scanning microscopy (LCSM). Statistical significance of differences in mean values was evaluated by Student's t tests. P < 0.05 was considered statistically significant.</p><p><b>RESULTS</b>In MCF-7/AdrA cells transfected with MDR1-A and MDR1-B shRNA expression vectors, RT-PCR showed that MDR1 mRNA expression was reduced by 40.9% (P < 0.05), 30.1% (P < 0.01) (transient transfection) and 37.6% (P < 0.05), 28.0% (P < 0.01) (stable transfection), respectively. Western Blot and immunocytochemistry showed that P-gp expression was significantly and specifically inhibited. Resistance against doxorubicin was decreased from 162-fold to 109-fold (P < 0.05), 54-fold (P < 0.01) (transient transfection) and to 108-fold (P < 0.05), 50-fold (P < 0.01) (stable transfection). Furthermore, shRNA vectors significantly enhanced the cellular daunorubicin accumulation. The combination of shRNA vectors and doxorubicin significantly induced apoptosis in MCF-7/AdrR cells.</p><p><b>CONCLUSIONS</b>shRNA expression vectors effectively reduce MDR expression in a sustained fashion and can restore the sensitivity of drug-resistant cancer cells to conventional chemotherapeutic agents.</p>

Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs.

Carbamazepine (CBZ) and zonisamide (ZNS) are effective antiepileptic drugs (AEDs) for the treatment of epilepsy and mood disorder. One of the mechanisms of action of CBZ and ZNS is inactivation of voltage-gated Na+ channel (VGSC). However, the major mechanism(s) of action of these AEDs is not clear yet. We have been exploring novel targeting mechanisms for the antiepileptic actions of CBZ and ZNS during the past ten years. In this report, we describe our hypothesis regarding the new targeting mechanisms for the antiepileptic action of AEDs. We determined an interaction between these AEDs and inhibitors of both voltage-sensitive Ca2+ channels (VSCCs) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) on neurotransmitter exocytosis using microdialysis. Perfusion with therapeutic concentrations of CBZ and ZNS increased basal neurotransmitter release. This stimulatory action was predominantly inhibited by inhibitors of N-type VSCC and syntaxin. CBZ and ZNS increased Ca2+-evoked release, an action selectively inhibited by inhibitors of N-type VSCC and syntaxin. CBZ and ZNS reduced K+-evoked release, an action predominantly inhibited by inhibitors of P-type VSCCs and synaptobrevin. These actions of CBZ and ZNS on neurotransmitter exocytosis could be observed under the condition of inhibition of VGSC using perfusion with tetrodotoxin. Our findings enhance our understanding of the mechanisms of action of CBZ and ZNS as AEDs, which possibly reduce P-type VSCCs/synaptobrevin-related exocytosis mechanisms during the depolarization stage, and simultaneously enhance N-type VSCCs/syntaxin-related exocytosis mechanisms at the resting stage.