PSMA PET/CT SUVmax as a prognostic biomarker in patients with metachronous metastatic hormone-sensitive prostate cancer (mHSPC).

BACKGROUND: Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate 68Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy. MATERIAL AND METHODS: Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent 68 Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons. RESULTS: A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered. CONCLUSIONS: PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.

Revealing the CO Coverage-Driven C-C Coupling Mechanism for Electrochemical CO2 Reduction on Cu2O Nanocubes via Operando Raman Spectroscopy.

Electrochemical reduction of carbon dioxide (CO2RR) is an attractive route to close the carbon cycle and potentially turn CO2 into valuable chemicals and fuels. However, the highly selective generation of multicarbon products remains a challenge, suffering from poor mechanistic understanding. Herein, we used operando Raman spectroscopy to track the potential-dependent reduction of Cu2O nanocubes and the surface coverage of reaction intermediates. In particular, we discovered that the potential-dependent intensity ratio of the Cu-CO stretching band to the CO rotation band follows a volcano trend similar to the CO2RR Faradaic efficiency for multicarbon products. By combining operando spectroscopic insights with Density Functional Theory, we proved that this ratio is determined by the CO coverage and that a direct correlation exists between the potential-dependent CO coverage, the preferred C-C coupling configuration, and the selectivity to C2+ products. Thus, operando Raman spectroscopy can serve as an effective method to quantify the coverage of surface intermediates during an electrocatalytic reaction.

Nanostructure of nickel-promoted indium oxide catalysts drives selectivity in CO2 hydrogenation.

Metal promotion in heterogeneous catalysis requires nanoscale-precision architectures to attain maximized and durable benefits. Herein, we unravel the complex interplay between nanostructure and product selectivity of nickel-promoted In2O3 in CO2 hydrogenation to methanol through in-depth characterization, theoretical simulations, and kinetic analyses. Up to 10 wt.% nickel, InNi3 patches are formed on the oxide surface, which cannot activate CO2 but boost methanol production supplying neutral hydrogen species. Since protons and hydrides generated on In2O3 drive methanol synthesis rather than the reverse water-gas shift but radicals foster both reactions, nickel-lean catalysts featuring nanometric alloy layers provide a favorable balance between charged and neutral hydrogen species. For nickel contents >10 wt.%, extended InNi3 structures favor CO production and metallic nickel additionally present produces some methane. This study marks a step ahead towards green methanol synthesis and uncovers chemistry aspects of nickel that shall spark inspiration for other catalytic applications.

Emergence of Potential-Controlled Cu-Nanocuboids and Graphene-Covered Cu-Nanocuboids under Operando CO2 Electroreduction.

The electroreduction of CO2 (CO2RR) is a promising strategy toward sustainable fuels. Cu is the only Earth-abundant and pure metal capable of catalyzing CO2-to-hydrocarbons conversion with significant Faradaic efficiencies; yet, its dynamic structure under operando CO2RR conditions remains unknown. Here, we track the Cu structure operando by electrochemical scanning tunneling microscopy and Raman spectroscopy. Surprisingly, polycrystalline Cu surfaces reconstruct forming Cu nanocuboids whose size can be controlled by the polarization potential and the time employed in their in situ synthesis, without the assistance of organic surfactants and/or halide anions. If the Cu surface is covered by a graphene monolayer, smaller features with enhanced catalytic activity for CO2RR can be prepared. The graphene-protecting layer softens the 3D morphological changes that Cu-based catalysts suffer when exposed to aggressive electrochemical environments and allows us to track the kinetic roughening process. This novel strategy is promising for improving Cu long-term stability, and consequently, it could be used as a platform to ultimately control product selectivity.

Electrochemical Reduction of Carbon Dioxide to 1-Butanol on Oxide-Derived Copper.

The electroreduction of carbon dioxide using renewable electricity is an appealing strategy for the sustainable synthesis of chemicals and fuels. Extensive research has focused on the production of ethylene, ethanol and n-propanol, but more complex C4 molecules have been scarcely reported. Herein, we report the first direct electroreduction of CO2 to 1-butanol in alkaline electrolyte on Cu gas diffusion electrodes (Faradaic efficiency=0.056 %, j1-Butanol =-0.080 mA cm-2 at -0.48 V vs. RHE) and elucidate its formation mechanism. Electrolysis of possible molecular intermediates, coupled with density functional theory, led us to propose that CO2 first electroreduces to acetaldehyde-a key C2 intermediate to 1-butanol. Acetaldehyde then undergoes a base-catalyzed aldol condensation to give crotonaldehyde via electrochemical promotion by the catalyst surface. Crotonaldehyde is subsequently electroreduced to butanal, and then to 1-butanol. In a broad context, our results point to the relevance of coupling chemical and electrochemical processes for the synthesis of higher molecular weight products from CO2 .

Quasi-degenerate states and their dynamics in oxygen deficient reducible metal oxides.

The physical and chemical properties of oxides are defined by the presence of oxygen vacancies. Experimentally, non-defective structures are almost impossible to achieve due to synthetic constraints. Therefore, it is crucial to account for vacancies when evaluating the characteristics of these materials. The electronic structure of oxygen-depleted oxides deeply differs from that of the native forms, in particular, of reducible metal oxides, where excess electrons can localize in various distinct positions. In this perspective, we present recent developments from our group describing the complexity of these defective materials that highlight the need for an accurate description of (i) intrinsic vacancies in polar terminations, (ii) multiple geometries and complex electronic structures with several states attainable at typical working conditions, and (iii) the associated dynamics for both vacancy diffusion and the coexistence of more than one electronic structure. All these aspects widen our current understanding of defects in oxides and need to be adequately introduced in emerging high-throughput screening methodologies.

Statistical learning goes beyond the d-band model providing the thermochemistry of adsorbates on transition metals.

The rational design of heterogeneous catalysts relies on the efficient survey of mechanisms by density functional theory (DFT). However, massive reaction networks cannot be sampled effectively as they grow exponentially with the size of reactants. Here we present a statistical principal component analysis and regression applied to the DFT thermochemical data of 71 C[Formula: see text]-C[Formula: see text] species on 12 close-packed metal surfaces. Adsorption is controlled by covalent ([Formula: see text]-band center) and ionic terms (reduction potential), modulated by conjugation and conformational contributions. All formation energies can be reproduced from only three key intermediates (predictors) calculated with DFT. The results agree with accurate experimental measurements having error bars comparable to those of DFT. The procedure can be extended to single-atom and near-surface alloys reducing the number of explicit DFT calculation needed by a factor of 20, thus paving the way for a rapid and accurate survey of whole reaction networks on multimetallic surfaces.

Atomic-scale engineering of indium oxide promotion by palladium for methanol production via CO2 hydrogenation.

Metal promotion is broadly applied to enhance the performance of heterogeneous catalysts to fulfill industrial requirements. Still, generating and quantifying the effect of the promoter speciation that exclusively introduces desired properties and ensures proximity to or accommodation within the active site and durability upon reaction is very challenging. Recently, In2O3 was discovered as a highly selective and stable catalyst for green methanol production from CO2. Activity boosting by promotion with palladium, an efficient H2-splitter, was partially successful since palladium nanoparticles mediate the parasitic reverse water-gas shift reaction, reducing selectivity, and sinter or alloy with indium, limiting metal utilization and robustness. Here, we show that the precise palladium atoms architecture reached by controlled co-precipitation eliminates these limitations. Palladium atoms replacing indium atoms in the active In3O5 ensemble attract additional palladium atoms deposited onto the surface forming low-nuclearity clusters, which foster H2 activation and remain unaltered, enabling record productivities for 500 h.

Origin of the Selective Electroreduction of Carbon Dioxide to Formate by Chalcogen Modified Copper.

The electrochemical reduction of atmospheric CO2 by renewable electricity opens new routes to synthesize fuels and chemicals, but more selective and efficient catalysts are needed. Herein, by combining experimental and first-principles studies, we explain why chalcogen modified copper catalysts are selective toward formate as the only carbon product. On the unmodified copper, adsorbed CO2 is the key intermediate, yielding carbon monoxide and formate as carbon products. On sulfur, selenium, or tellurium modified copper, chalcogen adatoms are present on the surface and actively participate in the reaction, either by transferring a hydride or by tethering CO2 thus suppressing the formation of CO. These results highlight the active role of chalcogen centers via chemical steps and point toward basicity as the key descriptor for the stability and selectivity of these catalysts.

Microkinetics of alcohol reforming for H2 production from a FAIR density functional theory database.

The large-scale production of hydrogen from biomass under industrial conditions is fundamental for a sustainable future. Here we present a multiscale study of the available reforming technologies based on a density functional theory open database that allows the formulation of linear scaling relationships and microkinetics. The database fulfills the FAIR criteria: findability, accessibility, interoperability and reusability. Moreover, it contains more than 1000 transition states for the decomposition of C2 alcohols on close-packed Cu, Ru, Pd, and Pt surfaces. The microkinetic results for activity, selectivity toward H2, and stability can be directly mapped to experiments, and the catalytic performance is controlled by various types of poisoning. Linear scaling relationships provide valid quantitative results that allow the extrapolation to larger compounds like glycerol. Our database presents a robust roadmap to investigate the complexity of biomass transformations through the use of small fragments as surrogates when investigated under different reaction conditions.

Initial Stages in the Formation of Nickel Phosphides.

Metal phosphides have emerged as a new powerful class of materials that can be employed as heterogeneous catalysts in transformations mainly to generate new energy vectors and the valorization of renewables. Synthetic protocols based on wet techniques are available and are based on the decomposition of the organic layer decorating the nanoparticles. For nickel, the phosphine of choice is trioctylphosphine, and this leads to the formation of NiPx materials. However, the temperature at which the decomposition starts has been found to depend on the quality of the nickel surface. Density functional theory, DFT, holds the key to analyze the initial steps of the formation of these phosphide materials. We have found how clean nickel surfaces, either (111) or (100), readily breaks the ligand P-C bonds. This triggers the process that leads to the replacement of a surface nickel atom by P and concomintantly forms a Ni adatom on the surface surrounded by two methyl groups, thus starting the formation of the NiPx phase. The whole process requires low energies, in agreement with the low temperature found in the experiments, 150 °C. In contrast, if the surface is oxidized, the reaction does not proceed at low temperatures and oxygen vacancies need to be created first to start the P-C bond breaking on the Ni-clean patches. Our results show that the cleaner the surface is, the milder the reactions are required for the NiPx formation, and thus they pave the way for gentler synthetic protocols that can improve the control of these materials.

Diversity at the Water-Metal Interface: Metal, Water Thickness, and Confinement Effects.

The structure and properties of water films in contact with metal surfaces are crucial to understand the chemical and electrochemical processes involved in energy-related technologies. The nature of thin water films on Pd, Pt, and Ru has been investigated by first-principles molecular dynamics to assess how the chemistry at the water-metal surface is responsible for the diversity in the behavior of the water layers closer to the metal. The characteristics of liquid water: the radial distribution functions, coordination, and fragment speciation appear only for unconfined water layers of a minimum of 1.4 nm thick. In addition, the water layer is denser in the region closest to the metal for Pd and Pt, where seven- and five-membered ring motifs appear. These patterns are identical to those identified by scanning tunneling microscopy for isolated water bilayers. On Ru densification at the interface is not observed, water dissociates, and protons and hydroxyl groups are locked at the surface. Therefore, the acid-base properties in the area close to the metal are not perturbed, in agreement with experiments, and the bulk water resembles an electric double layer. Confinement affects water making it closer to ice for both structural and dynamic properties, thus being responsible for the higher viscosity experimentally found at the nanoscale. All these contributions modify the solvation of reactants and products at the water-metal interface and will affect the catalytic and electrocatalytic properties of the surface.

Treatment of facial cutaneous carcinoma with high-dose rate contact brachytherapy with customized molds.

BACKGROUND: The main treatment given for initial stage facial epitheliomas is surgery, although there are alternatives. We present our results with Ir-192 high-dose rate (HDR) contact brachytherapy. METHODS AND MATERIALS: Fifty-one epitheliomas, with a mean size of 1.5 cm and a maximum thickness of 3mm, were treated with HDR contact brachytherapy by means of customized molds, with plastic tubes on bolus for flat surfaces and on wax molds for the nose. A total dose of 48-57 Gy, 3-4 Gy/fraction three times a week, was administered. RESULTS: After a median followup of 45 months, five tumors relapsed (9.8%), four of them on the tip of the nose. The 5-year actuarial local control rate was 89%, 100% for flat surfaces, and 83% for the nose. All of them were salvaged with surgery. The treatment was well tolerated, 21.6% developed severe acute toxicity, with good or very good late cosmetic results. CONCLUSION: HDR contact brachytherapy is a good alternative to treat facial epitheliomas with a maximum thickness of 3mm. Tip of the nose tumors are not well covered with this technique and a different procedure is required.

Efficacy of high-dose-rate interstitial brachytherapy in patients with oral tongue carcinoma.

PURPOSE: To evaluate the results of high-dose-rate (HDR)-interstitial brachytherapy (ISBT) in oral tongue carcinomas. METHODS AND MATERIALS: Between September 1999 and August 2007, 50 patients were treated for oral tongue carcinoma with HDR-ISBT. The patient's mean age was 58 years. Forty-two patients were in T1-2 stage and 8 patients were in T3 stage; 16 patients were in N+ stage and 34 patients in N0 stage. Exclusive ISBT was given to 17 patients (34%) in T1-2 N0 stage and complementary to external beam radiotherapy (EBRT) to 33 patients (66%). A perioperative technique was performed on 14 patients. The median total dose was 44 Gy when HDR was used alone (4 Gy per fraction) and 18 Gy when complementary to 50 Gy EBRT (3 Gy per fraction). RESULTS: The median followup was 44 months. Actuarial disease-free survival rates at 3 and 5 years were 81% and 74%, respectively. Local failure developed in 7 patients. Actuarial local control (LC) rates were 87% and 79% at 3 and 5 years in T1-2 stage 94.5% and 91% and T3 stage 43% and 43% (with salvage surgery). Exclusive HDR cases showed LC in 100% of the cases, and the combined group (EBRT+HDR) showed LC in 80% and 69% of the cases at 3 and 5 years (p=0.044). Soft-tissue necrosis developed in 16% and bone necrosis in 4% of the cases. CONCLUSIONS: HDR brachytherapy is an effective method for the treatment of oral tongue carcinoma in low-risk cases. Doses per fraction between 3 and 4 Gy yield LC and complication rates similar to low-dose rate. The perioperative technique promises encouraging results.