Organic Uptake Research Articles

Synthesis and preclinical evaluation of [18F]AlF-NOTA-Asp2-PEG2-JR11 as a novel antagonist radioligand for PET imaging of somatostatin receptor.

Somatostatin receptor (SSTR) antagonists have recently emerged as preferable radiotracers for SSTR-targeted imaging and therapy. This study aimed to design a novel SSTR antagonist, [18F]AlF-NOTA-Asp2-PEG2-JR11, and compare its preclinical performance with the previously reported antagonist, [18F]AlF-NOTA-JR11, and the agonist [68Ga]Ga-DOTA-TATE. [18F]AlF-NOTA-Asp2-PEG2-JR11 was synthesized via a one-step radiolabeling process involving [18F]AlF chelation. The binding affinity, internalization, and cellular uptake were evaluated using AR42J/SSTR + cells. Biodistribution and PET/CT imaging were conducted in mice bearing xenografted AR42J/SSTR + or HCT116/SSTR- tumor xenografts. [18F]AlF-NOTA-Asp2-PEG2-JR11 was manually synthesized within 30min with an uncorrected radiochemical yield of 39.56 ± 3.25% (n > 5) and radiochemical purity (RCP) exceeding 99% (n > 5). [18F]AlF-NOTA-Asp2-PEG2-JR11 demonstrated excellent in vivo stability over 2h (RCP > 95%). Among AR42J cells, [18F]AlF-NOTA-Asp2-PEG2-JR11 exhibited high affinity, specific uptake, and low internalization, similar to [18F]AlF-NOTA-JR11. Biodistribution and micro-PET/CT imaging studies revealed comparable tumor uptake between [18F]AlF-NOTA-Asp2-PEG2-JR11 and [18F]AlF-NOTA-JR11 (9.26 ± 0.49 vs. 10.18 ± 0.82%ID/g, p = 0.147) at 60min post-injection (p.i), both were significantly higher than [68Ga]Ga-DOTA-TATE (6.79 ± 0.29%ID/g, p = 0.001). Co-injecting the corresponding inhibitor significantly reduced the tumor uptake of all three tracers. Notably, [18F]AlF-NOTA-Asp2-PEG2-JR11 reached peak tumor uptake at 30min p.i. and exhibited the lowest uptake and fastest clearance in most normal organs, including the kidney, bone, liver, and muscle, resulting in the highest and increasing tumor-to-background ratios (TBR) over time among the three tracers. The synthesis of [18F]AlF-NOTA-Asp2-PEG2-JR11 is efficient, with high radiochemical yield and RCP. [18F]AlF-NOTA-Asp2-PEG2-JR11 exhibits excellent in vivo stability, high tumor uptake, and superior TBR, making it a promising potential tracer for imaging SSTR-positive tumors.

Organic matter processing by heterotrophic bacterioplankton in a large tropical river: Relating elemental composition and potential carbon mineralization.

River hydrology shapes the sources, concentration, and stoichiometry of organic matter within drainage basins. However, our understanding of how the microbes process dissolved organic matter (DOM) and recycle nutrients in tropical rivers needs to be improved. This study explores the relationships between elemental DOM composition (carbon/nitrogen/phosphorus: C/N/P), C and N uptake, and C mineralization by autochthonous bacterioplankton in the Usumacinta River, one of the most important fluvial systems in Mexico. Our study investigated changes in the composition and concentration of DOM and evaluated carbon dioxide (CO2)production rates (C-CO2) through laboratory experiments. We compared three sites representing the middle and lower river basins, including their transitional zones, during the rainy and dry seasons. After incubation (120 h at 25°C), the DOM decreased between 25% and 89% of C content. Notably, the initial high proportion of C in DOM in samples from the middle-forested zone and the transition led to elevated C-CO2 rates (>10 mg l-1 day-1), in contrast to the lower initial C proportion and subsequent C-CO2 rates (<7 mg l-1 day-1) in the lower river basin. We also found that dissolved organic carbon uptake and NO3- and NH4+ production were higher during the dry season than in the rainy season. The low water flow in the river during the dry season accentuated the differences in elemental composition and microbial processing of DOM among the sites, while the high water flow of the rainy season homogenized these factors. Our findings indicate that microbial metabolism operates with reduced efficiency in C-rich environments like forests, particularly when faced with high C/N and C/P ratios in DOM. This study highlights the influence of the tropical hydrological regime (rainy and dry seasons) and the longitudinal changes in the river basin (middle and lower) topography and land cover on microbial metabolism by constraining DOM characteristics, emphasizing the crucial role of elemental ratios in river DOM processing.

Novel [18F]FPG-interleukin-2 conjugate for monitoring immune checkpoint therapy with positron emission tomography

18F-interleukin-2 based PET imaging of activated T cells serves as a potential tool for non-invasive response prediction, treatment evaluation, and patient stratification in cancer immune checkpoint therapy. Herein, we report the radiolabelling of interleukin-2 (IL-2) with a novel arginine selective bioconjugation reagent, 4-[18F]fluorophenylglyoxal ([18F]FPG). Good non-decay corrected bioconjugation efficiencies of 29 ± 4 % (n = 5) were obtained for the [18F]FPG-IL-2. [18F]FPG-IL-2 uptake by the phytohemagglutinin-activated Jurkat cells (50.5 ± 1.2 %, n = 3) was significantly higher compared to the non-activated Jurkat cells (12.9 ± 1.1 %, n = 3). The [18F]FPG-IL-2 uptake was blocked by the pre-treatment of activated Jurkat cells with excess native IL-2 (22.3 ± 2.2 %, n = 3). Dynamic PET imaging and ex vivo biodistribution study of [18F]FPG-IL-2 in healthy and CT26 tumour bearing mice demonstrated hepatobiliary and renal clearance with minimal uptake in other organs and CT26 tumours. [18F]FPG-IL-2 PET imaging was applied to non-invasively monitor immune checkpoint therapy in CT26 tumour bearing mice, treated with IgG (control), ⍺PD-1 (monotherapy), and ⍺PD-1+⍺CTLA-4 (combination therapy). Significant uptake was observed in the spleens and tumours of the mice in the combination therapy group, which was associated with increased cytotoxic CD8+ T-cell infiltration and reduced tumour volumes. [18F]FPG-IL-2 based PET imaging has the potential to monitor immune checkpoint therapy.

Anthropogenic Extremely Low Volatility Organics (ELVOCs) Govern the Growth of Molecular Clusters Over the Southern Great Plains During the Springtime

AbstractNew particle formation (NPF) often drives cloud condensation nuclei concentrations and the processes governing nucleation of molecular clusters vary substantially in different regions. The growth of these clusters from ∼2 to &gt;10 nm diameters is often driven by the availability of extremely low volatility organic vapors (ELVOCs). Although the pathways to ELVOC formation from the oxidation of biogenic terpenes are better understood, the mechanistic pathways for ELVOC formation from oxidation of anthropogenic organics are less well understood. We integrate measurements and detailed regional model simulations to understand the processes governing NPF and secondary organic aerosol formation at the Southern Great Plain (SGP) observatory in Oklahoma and compare these with a site within the Bankhead National Forest (BNF) in Alabama, southeast USA. During our two simulated NPF event days, nucleation rates are predicted to be at least an order of magnitude higher at SGP compared to BNF largely due to lower sulfuric acid (H2SO4) concentrations at BNF. Among the different nucleation mechanisms in WRF‐Chem, we find that the dimethylamine (DMA) + H2SO4 nucleation mechanism dominates at SGP. We find that anthropogenic ELVOCs are critical for explaining the growth of particles observed at SGP. Treating organic particles as semisolid, with strong diffusion limitations for organic vapor uptake in the particle phase, brings model predictions into closer agreement with observations. We also simulate two non‐NPF event days observed at the SGP site and show that low‐level clouds reduce photochemical activity with corresponding reductions in H2SO4 and anthropogenic ELVOC concentrations, thereby explaining the lack of NPF.

The relationship between lung MIBG uptake and clinical response to renal denervation

Abstract Background Renal denervation (RDN) reduces the sympathetic overdrive and can optimize blood pressure control in patients with difficult-to-treat hypertension (DTH). However, a substantial proportion of patients undergoing RDN do not show a clinical response to the procedure, making it critical to identify novel and more accurate predictors. The metaiodobenzylguanidine (MIBG) scintigraphy allows non-invasive assessment of sympathetic nerve activity. Yet, studies evaluating the heart and kidney MIBG uptake as predictors of clinical response to RDN provided conflicting results, and a comprehensive evaluation of the MIBG uptake in different organs of DTH patients undergoing RDN is lacking. Purpose To explore if a more comprehensive evaluation of MBG uptake in the kidneys, heart and lungs can predict the clinical response to RDN. Methods Eighteen patients with DTH underwent evaluation of their clinical and pharmacological history, office and ambulatory BP values and levels of cardiovascular risk factors. A rest echocardiography, carotid vascular ultrasound and MIBG scintigraphy were also performed before RDN. The patient’s pharmacological history and office and ambulatory BP values were re-evaluated after 3 months from RDN. We considered responders (R) those subjects with a significant reduction of the office BP values on stable BP-lowering treatment or a reduced burden of BP-lowering medications while maintaining optimal control of the office BP. Results Ten patients could be classified as R (1 woman, mean age 49±10 years), while 7 were non-responders (NR, 2 women, mean age 53±8 years). The reduction in office systolic and diastolic BP (baseline vs 3 months) was significantly larger in R vs NR (p=0.01 for both). The burden of BP-lowering medications after the procedure was reduced by 39% in R, compared to 2% in NR (p&amp;lt;0.01). Responders had a higher baseline HR and prevalence of carotid atherosclerosis than NR (p&amp;lt;0.05 for both). In early MIBG acquisitions, the lung/mediastinum ratio on both sides showed higher MIBG uptake in R vs NR (p&amp;lt;0.05). There was a higher MIBG uptake in the right vs. left lung in the whole population and in R vs NR. In late acquisitions, only the left side showed a significant difference between R and NR (p&amp;lt;0.05). The associations between the lung/mediastinum ratio MIBG uptake and response to RDN remained significant after adjusting for the baseline clinical predictors of the RDN response. All other MIBG scintigraphy parameters were similar between groups. Conclusions Our results suggest that RDN might be less effective in patients with an advanced burden of hypertension-mediated target organ damage and confirm a higher HR as a reliable predictor of the clinical response to the procedure. We also document a novel association between the lung/mediastinum ratio MIBG uptake and response to RDN that, if confirmed in future studies, might provide a novel marker to improve the selection of patients undergoing RDN.

First-in-human study of dosimetry, safety and efficacy for [177Lu]Lu-P15-073: a novel bisphosphonate-based radioligand therapy (RLT) agent for bone metastases.

Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [177Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases. Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [177Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [99mTc]Tc-MDP bone scans. Serial planar whole-body scans monitored biodistribution over a 14-day period. Dosimetry was assessed for major organs and tumor lesions, while safety was evaluated through blood biomarkers and pain scores. Serial planar whole-body scans demonstrated rapid and substantial accumulation of [177Lu]Lu-P15-073 in bone metastases, with minimal uptake in blood and other organs. The absorbed dose in the critical organ, red marrow, was measured at (0.034 ± 0.010 mSv/MBq), with a notably low normalized effective dose (0.013 ± 0.005 mSv/MBq) compared to other 177Lu-labeled bisphosphonates. Persistent high uptake in bone metastases was observed, resulting in elevated tumor doses (median 3.12Gy/GBq). Patients exhibited favorable tolerance to [177Lu]Lu-P15-073 therapy, with no new instances of side effects. Additionally, 87.5% (7/8) of patients experienced a significant reduction in pain scale (numerical rating scale, NRS, from 5.1 ± 2.3 to 3.0 ± 1.8). The tumor-background ratio (TBRmean) of [99mTc]Tc-MDP correlated significantly with [177Lu]Lu-P15-073 uptake (P < 0.01), indicating its potential for prediction of absorbed dose. This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [177Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [177Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.

Dual-labeled anti-GD2 targeted probe for intraoperative molecular imaging of neuroblastoma

BackgroundSurgical resection is integral for the treatment of neuroblastoma, the most common extracranial solid malignancy in children. Safely locating and resecting primary tumor and remote deposits of disease remains a significant challenge, resulting in high rates of complications and incomplete surgery, worsening outcomes. Intraoperative molecular imaging (IMI) uses targeted radioactive or fluorescent tracers to identify and visualize tumors intraoperatively. GD2 was selected as an IMI target, as it is highly overexpressed in neuroblastoma and minimally expressed in normal tissue.MethodsGD2 expression in neuroblastoma cell lines was measured by flow cytometry. DTPA and IRDye® 800CW were conjugated to anti-GD2 antibody to generate DTPA-αGD2-IR800. Binding affinity (Kd) of the antibody and the non-radiolabeled tracer were then measured by ELISA assay. Human neuroblastoma SK-N-BE(2) cells were surgically injected into the left adrenal gland of 3.5-5-week-old nude mice and the orthotopic xenograft tumors grew for 5 weeks. 111In-αGD2-IR800 or isotype control tracer was administered via tail vein injection. After 4 and 6 days, mice were euthanized and gamma and fluorescence biodistributions were measured using a gamma counter and ImageJ analysis of acquired SPY-PHI fluorescence images of resected organs (including tumor, contralateral adrenal, kidneys, liver, muscle, blood, and others). Organ uptake was compared by one-way ANOVA (with a separate analysis for each tracer/day combination), and if significant, Sidak’s multiple comparison test was used to compare the uptake of each organ to the tumor. Handheld tools were also used to detect and visualize tumor in situ, and to assess for residual disease following non-guided resection.Results111In-αGD2-IR800 was successfully synthesized with 0.75-2.0 DTPA and 2–3 IRDye® 800CW per antibody and retained adequate antigen-binding (Kd = 2.39 nM for aGD2 vs. 21.31 nM for DTPA-aGD2-IR800). The anti-GD2 tracer demonstrated antigen-specific uptake in mice with human neuroblastoma xenografts (gamma biodistribution tumor-to-blood ratios of 3.87 and 3.88 on days 4 and 6 with anti-GD2 tracer), while isotype control tracer did not accumulate (0.414 and 0.514 on days 4 and 6). Probe accumulation in xenografts was detected and visualized using widely available operative tools (Neoprobe® and SPY-PHI camera) and facilitated detection ofputative residual disease in the resection cavity following unguided resection.ConclusionsWe have developed a dual-labeled anti-GD2 antibody-based tracer that incorporates In-111 and IRDye® 800CW for radio- and fluorescence-guided surgery, respectively. The tracer adequately binds to GD2, specifically accumulates in GD2-expressing xenograft tumors, and enables tumor visualization with a hand-held NIR camera. These results encourage the development of 111In-αGD2-IR800 for future use in children with neuroblastoma, with the goal of improving patient safety, completeness of resection, and overall patient outcomes.

Automatic detection and segmentation of lesions in 18 F-FDG PET/CT imaging of patients with Hodgkin lymphoma using 3D dense U-Net.

The accuracy of automatic tumor segmentation in PET/computed tomography (PET/CT) images is crucial for the effective treatment and monitoring of Hodgkin lymphoma. This study aims to address the challenges faced by certain segmentation algorithms in accurately differentiating lymphoma from normal organ uptakes due to PET image resolution and tumor heterogeneity. Variants of the encoder-decoder architectures are state-of-the-art models for image segmentation. Among these kinds of architectures, U-Net is one of the most famous and predominant for medical image segmentation. In this study, we propose a fully automatic approach for Hodgkin lymphoma segmentation that combines U-Net and DenseNet architectures to reduce network loss for very small lesions, which is trained using the Tversky loss function. The hypothesis is that the fusion of these two deep learning models can improve the accuracy and robustness of Hodgkin lymphoma segmentation. A dataset with 141 samples was used to train our proposed network. Also, to test and evaluate the proposed network, we allocated two separate datasets of 20 samples. We achieved 0.759 as the mean Dice similarity coefficient with a median value of 0.767, and interquartile range (0.647-0.837). A good agreement was observed between the ground truth of test images against the predicted volume with precision and recall scores of 0.798 and 0.763, respectively. This study demonstrates that the integration of U-Net and DenseNet architectures, along with the Tversky loss function, can significantly enhance the accuracy of Hodgkin lymphoma segmentation in PET/CT images compared to similar studies.

An Excessive K/Na Ratio in Soil Solutions Impairs the Seedling Establishment of Sunflower (Helianthus annuus L.) through Reducing the Leaf Mg Concentration and Photosynthesis

In saline conditions, establishing healthy seedlings is crucial for the productivity of sunflowers (Helianthus annuus L.). Excessive potassium (K+) from irrigation water or overfertilization, similar to sodium (Na+), could adversely affect sunflower growth. However, the effects of salt stress caused by varying K/Na ratios on the establishment of sunflower seedlings have not been widely studied. We conducted a pot experiment in a greenhouse, altering the K/Na ratio of a soil solution to grow sunflower seedlings. We tested three saline solutions with K/Na ratios of 0:1 (P0S1), 1:1 (P1S1), and 1:0 (P1S0) at a constant concentration of 4 dS m−1, along with a control (CK, no salt added), with five replicates. The solutions were applied to the pots via capillary rise through small holes at the bottom. The results indicate that different K/Na ratios significantly influenced ion-selective uptake and transport in crop organs. With an increasing K/Na ratio, the K+ concentration in the roots, stems, and leaves increased, while the Na+ concentration decreased in the roots and stems, with no significant differences in the leaves. Furthermore, an excessive K/Na ratio (P1S0) suppressed the absorption and transportation of Mg2+, significantly reducing the Mg2+ concentration in the stems and leaves. A lower leaf Mg2+ concentration reduced chlorophyll concentration, impairing photosynthetic performance. The lowest plant height, leaf area, dry matter, and shoot/root ratio were observed in P1S0, with reductions of 27%, 48%, 48%, and 13% compared to CK, respectively. Compared with CK, light use efficiency and CO2 use efficiency in P1S0 were significantly reduced by 13% and 10%, respectively, while water use efficiency was significantly increased by 9%. Additionally, improved crop morphological and photosynthetic performance was observed in P1S1 and P0S1 compared with P1S0. These findings underscore the critical role of optimizing ion composition in soil solutions, especially during the sensitive seedling stage, to enhance photosynthesis and ultimately to improve the plant’s establishment. We recommend that agricultural practices in saline regions incorporate tailored irrigation and fertilization strategies that prioritize optimal K/Na ratios to maximize crop performance and sustainability.

The emerging application of LC-based metallomics techniques to unravel the bioinorganic chemistry of toxic metal(loid)s

The on-going anthropogenic emission of toxic metal(loid) species into the environment contaminates the food supply and drinking water resources in various parts of the world. Given that inorganic pollutants cannot be degraded, their increased influx into the bloodstream of babies, children and pregnant women is inevitable. Since the ramifications of the ensuing environmental exposure on human health remain poorly defined, fundamentally new insight into their bioinorganic chemistry in organisms is urgently needed. Based on the flow of dietary constituents through organisms, the interaction of toxic metal(loid) species with biomolecules in the bloodstream deserve particular attention as they play an integral role in the mechanisms of their chronic toxicity. Gaining insight into these bioinorganic processes is hampered by the biological complexity of plasma/red blood cells and the low concentrations of the metal(loid) species of interest, but can be overcome by employing LC techniques hyphenated to atomic spectroscopic detectors (i.e. metallomics techniques). This perspective aims to highlight the potential of unconventional hyphenated separation modes to advance our understanding of the bioinorganic chemistry of toxic metal(loid) species in the bloodstream-organ system. Four examples are illustrated. The application of anion-exchange (AEX) and size-exclusion chromatography (SEC) provided new insight into the blood-based bioinorganic mechanisms that direct Cd2+ and MeHg+ to target organs. AEX chromatography also allowed to observe the formation of complexes between Hg2+ and MeHg+ with L-cysteine at pH 7.4, that are implicated in their organ uptake. Lastly, the application of reversed phase (RP) chromatography revealed a possible cytosolic mechanism by which N-acetyl-L-cysteine binds to MeHg+ in the presence of cytosolic glutathione (GSH). New insight into other bioinorganic processes may advance the regulatory framework to better protect public health.

The Development and Evaluation of a Novel Highly Selective PET Radiotracer for Targeting BET BD1.

Background/Objectives: Small molecules that interfere with the interaction between acetylated protein tails and the tandem bromodomains of BET (bromodomain and extra-terminal) family proteins are pivotal in modulating immune/inflammatory and neoplastic diseases. This study aimed to develop a novel PET imaging tracer, [11C]GSK023, that targets the N-terminal bromodomain (BD1) of BET family proteins with high selectivity and potency, thereby enriching the chemical probe toolbox for epigenetic imaging. Methods: [11C]GSK023, a radio-chemical probe, was designed and synthesized to specifically target the BET BD1. In vivo PET imaging evaluations were conducted on rodents, focusing on the tracer's distribution and binding specificity in various tissues. Blocking studies were performed to confirm the probe's selectivity and specificity. Results: The evaluations revealed that [11C]GSK023 demonstrated good uptake in peripheral organs with limited brain penetration. Further blocking studies confirmed the probe's high binding specificity and selectivity for the BET BD1 protein, underscoring its potential utility in epigenetic imaging. Conclusions: The findings suggest that [11C]GSK023 is a promising PET probe for imaging the BET BD1 protein, offering the potential to deepen our understanding of the roles of BET bro-modomains in disease and their application in clinical settings to monitor disease progression and therapeutic responses.

Technetium-99m radiolabeling of graphene quantum dots (GQDs) as a new probe for glioblastoma tumor imaging

Purpose Cancer diagnosis involves a multi-step process. Accurate identification of the tumor, staging and development of cancer cells is crucial for selecting optimal treatments to minimize disease recurrence. Quantum dots (QDs) represent an exciting class of fluorescent nanoprobes in molecular detection and targeted tumor imaging. Materials and methods In this study, graphene quantum dots (GQDs) were synthesized by pyrolysis of citric acid (CA) as a carbon precursor under high temperatures. The morphology of the obtained GQDs was first characterized using physical (TEM and DLS) and spectroscopic (fluorescence, FTIR and UV–Vis) methods. In the following,99mTc-labeled GQDs were prepared in the presence of SnCl2.2H2O as a reducing agent between 95 and 100 °C. The biodistribution and tumor targeting efficiency of radiolabeled GQDs as a novel agent for C6 glioma tumor scintigraphy in an animal model were evaluated. Furthermore, organ uptake, human serum albumin binding and tumor accumulation were measured. Results The TEM image of the prepared GQDs showed a relatively uniform size distribution in the range of diameter 6-9 nm and spherical shape. Radiolabeled GQDs showed a radiochemical yield of >97% (n = 3). Through incubation in human serum, almost 15% of 99mTc-labeled GQDs degraded after 6 h. The amount of uptake in xenograft models of glioma C6 rats was 1.10 ± 0.36% of injection dose per gram after 1 h. The kidneys, intestinal and glioma tumor sites were observed via scintigraphy imaging. Conclusion Our data suggest that 99mTc-labeled GQDs, as a new radiotracer, efficiently accumulate in the tumor site and could be included as a radiotracer for detecting glioma tumors.

Development of a Specifically Labeled 89Zr Antibody for the Noninvasive Imaging of Tumors Overexpressing B7-H3.

B7-H3 has emerged as a promising target and potential biomarker for diagnosing tumors, evaluating treatment efficacy, and determining patient prognosis. Hu4G4 is a recombinant humanized antibody that selectively targets the extracellular domain of human B7-H3. In this study, we describe the radiolabeling of hu4G4 with the positron emission tomography (PET) emitter radionuclide zirconium 89 (89Zr) and evaluate its potency as an immuno-PET tracer for B7-H3-targeted imaging by comparing it in vitro and in vivo to [89Zr]Zr-DFO-DS-5573a using various models. The radiolabeled compound, [89Zr]Zr-desferrioxamine-hu4G4 ([89Zr]Zr-DFO-hu4G4), demonstrated a high radiochemical purity (RCP) of greater than 99% and a specific activity of 74 MBq/mg following purification. Additionally, it maintained stability in human serum albumin (HSA) and acetate buffer, preserving over 90% of its RCP after 7 days. Three cell lines targeting human B7-H3(U87/CT26-CD276/GL261-CD276) were used. Flow cytometry analysis indicated that the B7-H3-positive cells (U87/CT26-CD276/GL261-CD276) had a higher B7-H3 protein level with no expression in the B7-H3-negative cells (CT26-wt/GL261-wt) (P < 0.001). Moreover, the cellular uptake was 45.71 ± 3.78% for [89Zr]Zr-DFO-hu4G4 in CT26-CD276 cells versus only 0.93 ± 0.47% in CT26-wt cells and 30.26 ± 0.70% when [89Zr]Zr-DFO-hu4G4 in CT26-CD276 cells were blocked with 100× 8H9. The cellular uptake of [89Zr]Zr-DFO-hu4G4 was akin to that observed with [89Zr]Zr-DFO-DS-5573a with no significant differences (45.71 ± 3.78 % vs 47.07 ± 0.86 %) in CT26-CD276 cells. Similarly, the CT26-CD276 mouse model demonstrated markedly low organ uptake and elevated tumor uptake 48 h after [89Zr]Zr-DFO-hu4G4 injection. PET/CT analysis showed that the tumor-to-muscle (T/M) ratios were substantially higher compared to other imaging groups: 27.65 ± 3.17 in CT26-CD276 mice versus 11.68 ± 4.19 in CT26-wt mice (P < 0.001) and 16.40 ± 0.78 when 100× 8H9 was used to block [89Zr]Zr-DFO-hu4G4 in CT26-CD276 mice (P < 0.01) at 48 h post-injection. Additionally, the tracer showed markedly high accumulation in the tumor region (22.57 ± 3.03% ID/g), comparable to the uptake of [89Zr]Zr-DFO-DS-5573a (24.76 ± 5.36% ID/g). A dosimetry estimation study revealed that the effective dose for [89Zr]Zr-DFO-hu4G4 was 2.96 × 10-01 mSv/MBq, which falls within the acceptable range for further research in nuclear medicine. Collectively, these results indicated that [89Zr]Zr-DFO-hu4G4 was successfully fabricated and applied in B7-H3-targeted tumor PET/CT imaging, which showed excellent imaging quality and tumor detection efficacy in tumor-bearing mice. It is a promising imaging agent for identifying tumors that overexpress B7-H3 for future clinical applications.

Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

Sustainable treatment of combined industrial wastewater: synergistic phytoremediation with Eichhornia crassipes, Pistia stratiotes, and Arundo donax in biofilm wetlands

This study investigates the treatment of combined wastewater from Hattar Industrial Estate using Biofilm Wetlands (BW) planted with monoculture species: Eichhornia crassipes (EAC), Pistia stratiotes (WL), and Arundo donax (GR). Each species showed distinct capabilities in organic degradation, metal uptake, and pH stabilization. BW2, planted with EAC, achieved the highest total solids (TS) and total suspended solids (TSS) removal efficiencies of 66% and 65%, respectively. GR effectively reduced initial COD concentrations from 232 mg/L to 58.67 mg/L, while EAC and WL reached reductions to 72.78 mg/L and 70.67 mg/L, respectively. Overall, the plant efficiency ranking was EAC > GR > WL. These findings underscore the potential of these plant species in synergistic BW systems, highlighting their role as natural solutions for remediating complex industrial effluents. This research contributes to advancing eco-friendly wastewater treatment approaches, suggesting promising applications for sustainable practices in industrial contexts. RESEARCH HIGHLIGHTS This research assessed the effectiveness of phytoremediation using Eichhornia crassipes, Pistia stratiotes, and Arundo donax for removing pollutants i.e. heavy metals (Cd, Pb, Ni, K, Ca, Mg, Na, Fe, Hg) nitrates, phosphates and sulfates from combined industrial wastewater of Hattar Industrial Estate Pakistan. It highlighted the potential of selected plant species’ as natural treatment systems, providing crucial insights into their efficiency. Findings contribute to understanding nature-based solutions for complex industrial effluents.

Dosimetry at cellular level for the alpha-emitting radionuclides actinium-225, astatine-211 and radium-223 for bone metastasis cells from castration resistant prostate cancer.

Objectives.The aim of this work is to evaluate energy deposition in the nucleus and cytoplasm in targeted alpha therapy of metastatic castration-resistant prostate cancer by modeling two cell lines, PC3 (osteolytic) and LNCaP C4-2 (osteoblastic), for actinium-225, astatine-211, and radium-223 and their progeny, using Monte Carlo simulations with the GATE/Geant4 code.Approach.We developed single cell and cell clusters models to Monte Carlo simulations, performed on the GATE platform version 9.3, with the GEANT4-DNA physics list emstandard_opt3_mixed_dna for At-211, Ac-225 and Ra-223 progenies. We considered three radionuclide distributions as a sources: the nucleus, the cytoplasm and the whole cell.Main results.When the nucleus was considered as a target, theS-values (N←N) calculated for At-211, Ac-225 and Ra-223 progenies were significantly higher, within 60%-90%, thanS-values (N←Cy), demonstrating less influence of cytoplasm only internalization. When the cytoplasm was considering as a target, theS-values (Cy←Cy) calculated for At-211, Ac-225 and Ra-223 progeny were significantly higher, within 30%-90%, than theS-values (Cy←N). When no progeny migration occurs and for target nucleus , the cumulativeS-values (N←N) calculated for At-211, Ac-225 and Ra-223 were significantly higher, within 50%-70%, than theS-values (N←N) computed for At-211, Ac-225, and Ra-223. Comparing the cumulativeS-values, Ac-225 and Ra-223 therapies is more effective, in terms of deposited energy in a target, than that with At-211.Significance.The data presented in this research indicates that Ac-225 therapy may be the optimum choice due to the energy deposited in the nucleus, as long as the recoil effects and redistribution of progeny are understood. In contrast, At-211 is an alternative to avoid progeny migration. However, to completely analyze the efficacy of radionuclide therapy, other parameters must be considered, such as biological half-life, stability of the transport molecule, progeny migration, excretion pathways, and uptake in different organs.

Drivers of microbial carbon biomass variability in two oceanic regions of the Gulf of Mexico

The microbial plankton community is an integral part of the pelagic ecosystem. It hosts essential functional groups that play a vital role in organic carbon production, release, uptake, and degradation within open-ocean ecosystems. Given its significance, carbon biomass estimates are urgently needed, especially in oligotrophic regions, to provide and enhance our knowledge of biogenic carbon pools. They also aid in validating biogeochemical models that characterize the functioning of these extensive marine ecosystems within the global carbon cycle. This study addresses the temporal variability of microbial community biomass in two oceanic zones: the west-central (Perdido) and southern (Coatzacoalcos) areas of the Gulf of Mexico. During three seasonally contrasting periods (nortes, rainy, and dry seasons), seawater samples were collected from the euphotic zone in both regions to estimate the carbon biomass of different pico- (<2–3 µm), nano-, and microplankton groups (>3–200 µm). Carbon biomass assessments for the microbial groups were based on their abundance and carbon conversion factors. Overall, we found a significant contribution of pico-prokaryotic components (heterotrophic bacteria, Prochloroccocus, and Synechoccocus) to the total microbial carbon stock of the euphotic zone (84–89 % global estimates). The finding suggests these microorganisms are key functional groups that drive carbon production and fate in the Gulf of Mexico ecosystem. Pico-cyanobacteria, especially Prochloroccocus, were the dominant primary producers (68–82 % total autotrophic carbon), mainly in the upper layer of the oligotrophic euphotic zone. This vertical pattern implies that the deep chlorophyll-a maximum (DCM) depth level was unrelated to a net increase in phytoplankton biomass in the three study periods. The distribution of microbial carbon biomass exhibited striking differences associated with winter mixing (the nortes season), high river discharge accompanied by cross-shelf transport (the rainy season), and the dynamics of mesoscale structures. Ecological aspects, such as the habitat preference of the organisms and the seasonal complementary development of mixotrophic and heterotrophic grazers and their prey, were also essential drivers in regulating the microbial carbon pool of both oceanic regions. The microbial carbon assessments conducted in this study contribute to identifying and quantifying key planktonic functional groups involved in the biogeochemical carbon cycle in the Gulf of Mexico open-ocean ecosystem.

Spontaneous Oxidation of Organic Matter and Ammonium Uptake from Manure Wastewater by Redox-Active Materials

Spontaneous Oxidation of Organic Matter and Ammonium Uptake from Manure Wastewater by Redox-Active Materials

A thiourea-bridged 99mTc(CO)3-dipicolylamine-2-nitroimidazole complex for targeting tumor hypoxia: Utilizing metabolizable thiourea-bridge to improve pharmacokinetics.

The 2-nitroimidazole based 99mTc-radiopharmaceuticals are widely explored for imaging tumor hypoxia. Radiopharmaceuticals for targeting hypoxia are often lipophilic and therefore, show significant uptake in liver and other vital organs. In this context, lipophilic radiopharmaceuticals with design features enabling faster clearance from liver may be more desirable. A dipicolylamine-NCS bifunctional chelator that could generate a thiourea-bridge up on conjugation to primary amine bearing molecule was used to synthesize a 2-nitroimidazole-dipicolyl amine ligand for radiolabeling with 99mTc(CO)3 core. Corresponding Re(CO)3-analogue was prepared to establish the structure of 2-nitroimidazole-99mTc(CO)3 complex prepared in trace level. The 2-nitroimidazole-99mTc(CO)3 complex showed a hypoxic to normoxic ratio of ~2.5 in CHO cells at 3 h. In vivo, the complex showed accumulation and retention in tumor with high tumor to blood and tumor to muscle ratio. The study demonstrated the utility of metabolizable thiourea-bridge in 2-nitroimidazole-99mTc(CO)3 complex in inducing faster clearance of the radiotracer from liver. The dipicolylamine-NCS bifunctional chelator reported herein can also be used for radiolabeling other class of target specific molecules with 99mTc(CO)3 core.

Bioenergetics disruption, oxidative stress, and inflammation as underlying mechanisms of tramadol-induced nephrotoxicity.

Tramadol (TR), a commonly prescribed pain reliever for moderate to severe pain, has been associated with kidney damage. This study investigates TR-induced nephrotoxicity mechanisms, focusing on its effects on renal proximal tubular cells (PTCs). The study findings demonstrate that TR disrupts PTC bioenergetic processes, leading to oxidative stress and inflammation. Significant toxicity to PTCs was observed with estimated effective concentration 50 values of 9.8 and 11.5 µM based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays, respectively. TR also interferes with the function of PTC transporters, including organic cation uptake transporter 1, organic cation transporter 2, P-glycoprotein, and multidrug resistance protein 2. Furthermore, bioenergetics assays showed that TR reduced the activities of mitochondrial complexes I and III, adenosine triphosphate production, mitochondrial membrane potential, and oxygen consumption rate while increasing lactate release. TR also increased the production of reactive oxygen species, lipid peroxidation thiobarbituric acid reactive substances end products, and the expression of the NRf2 gene while decreasing reduced glutathione (GSH-R) stores and catalase and superoxide dismutase antioxidant activities. Additionally, TR increased the production of inflammatory cytokines (TNF-α and IL-6) and their coding genes expression. Interestingly, the study found that antioxidants like GSH-R, inhibitors of IL-6 and TNF-α, and mitochondrial activating Co-Q10 could protect cells against TR-induced cytotoxicity. The study suggests that TR causes nephrotoxicity by disrupting bioenergetic processes, causing oxidative stress and inflammation, but antioxidants and agents targeting mitochondria may have protective and curative potential.