Uptake Ratio Research Articles

Enhancing malting performance of harder barley varieties through ultrasound treatment

Harder kernels of barley are regarded as one of the factors that restrict water and enzyme movement within the endosperm during malting. A comprehensive study of two domestic varieties was performed for evaluating malting quality. Both β-glucan and total protein content of the Chinese domestic barley (Ganpi-6 and Kenpi-14) were significantly higher than Copeland. Grain hardness of the Chinese domestic barley was higher and water uptake ratio was lower compared with the Copeland. During germination, the expression levels of NCED1, NCED2 (major key regulatory enzymes for abscisic acid biosynthesis genes) were higher, whereas gibberelic acid (GA) synthesis genes (GA20ox1, GA2ox3, GA3ox2) were lower in the Ganpi-6, Kenpi-14 compared with Copeland. These two domestic barley varieties also showed significantly lower limit dextrinase and β-glucanase activity compared with Copeland. Ultrasound treatment improved the malting quality of Ganpi-6 by enhancing water uptake and GA synthesis gene expression increased. Therefore, these findings provided insights into the future direction on the utilization of ultrasonication for the applications towards the improvement of the harder barley variety.

Dynamic multi-pinhole collimated brain SPECT of Parkinson’s disease by [123I]FP-CIT: a feasibility study of fSPECT

We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([123I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake values were corrected for partial volume effects. Specific binding ratio (SBRcalc) was calculated, reflecting binding potential relative to non-displaceable binding (BPND) in the cortex. Additional pharmacokinetic parameters (BPND, R1, k2) were estimated using the simplified reference tissue model, revealing differences between Kahraman low-score (LS) and high-score (HS) groups. Results showed increasing striatal tracer uptake until 100 min post-injection, with consistent values afterward. Uptake and SBRcalc ratios matched visual assessment. LS patients had lower putamen than caudate nucleus tracer uptake, decreased BPND values, while R1 and k2 values were comparable to HS patients. In conclusion, dynamic multi-pinhole SPECT using DaT tracer with the extraction of pharmacokinetic parameters is feasible and could help enable early differentiation of reduced and normal DaT values.

68Ga-FAPI PET/CT as an Alternative to 18F-FDG PET/CT in the Imaging of Invasive Lobular Breast Carcinoma.

Accurate staging of invasive lobular carcinoma (ILC), a subtype of breast cancer, is vital for effective clinical management. Although 18F-FDG PET/CT is a commonly used tool, its efficacy varies across different histologic subtypes. To mitigate this challenge, our investigation delves into the potential utility of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT as an alternative for staging ILC, aiming to address a significant research gap using a more expansive patient cohort than the smaller samples commonly found in the existing literature. Methods: In this retrospective analysis, women diagnosed with primary ILC of the breast underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/CT. Both modalities were compared across all lesion locations with the used reference standard. The interval between scans was 1 wk, without any intervening treatments. Lesions were categorized visually, and tracer activity was analyzed using SUVmax, tumor-to-background uptake ratio, and uptake ratios. Both modalities were compared across various parameters, and statistical analysis was performed using SPSS 22.0. A P value of less than 0.05 was chosen to determine statistical significance. Results: The study included 23 female ILC patients (mean age, 51 y) with hormone-positive, human epidermal growth factor receptor type 2-negative tumors. Most (65%) had the luminal A subtype. 68Ga-FAPI PET/CT outperformed 18F-FDG PET/CT, with higher tumoral activity and tumor-to-background uptake ratios (P < 0.001). Primary tumors showed significantly increased uptake with 68Ga-FAPI PET/CT (P < 0.001), detecting additional foci, including multicentric cancer. Axillary lymph node metastases were more frequent and had higher uptake values with 68Ga-FAPI PET/CT (P = 0.012). Moreover, 68Ga-FAPI PET/CT identified more lesions, including bone and liver metastases. Pathologic features did not significantly correlate with imaging modalities, but a positive correlation was observed between peritumoral lymphocyte ratio and 68Ga-FAPI PET/CT-to-18F-FDG PET/CT uptake ratios (P = 0.026). Conclusion: This study underscores 68Ga-FAPI PET/CT's superiority over 18F-FDG PET/CT for ILC. 68Ga-FAPI PET/CT excels in detecting primary breast masses, axillary lymph nodes, and distant metastases; can complement 18F-FDG PET/CT in ILC; and holds potential as an alternative imaging method in future studies.

18F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases.

The use of [18F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [18F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods: We recruited 18 patients with fILD awaiting lung biopsy for [18F]FDG PET/CT. We derived a target-to-background ratio (TBR) of maximum pulmonary uptake of [18F]FDG (SUVmax) divided by the lung background (SUVmin). Consecutive paraffin-embedded lung biopsy sections were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD) (CD31 and CD105/endoglin), and glucose transporter 1. MVD was expressed as vessel area percentage per high-power field (Va%/hpf). Differences in imaging and angiogenesis markers between histologic usual interstitial pneumonia (UIP) and non-UIP were assessed using a nonparametric Mann-Whitney test. Correlation of imaging with angiogenesis markers was assessed using the nonparametric Spearman rank correlation. Univariate Kaplan-Meier survival analysis assessed the difference in the survival curves for each of the angiogenesis markers (separated by their respective optimal cutoff) using the log-rank test. Statistical analysis was performed using SPSS. Results: In total, 18 patients were followed for an average of 41.36 mo (range, 5.69-132.46 mo; median, 30.07 mo). Only CD105 MVD showed a significantly positive correlation with [18F]FDG TBR (Spearman rank correlation, 0.556; P < 0.05, n = 13). There was no correlation between [18F]FDG uptake and macrophage expression of glucose transporter 1. CD105 and CD31 were higher for UIP than for non-UIP, with CD105 reaching statistical significance (P = 0.011). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with CD105 MVD of less than 12 Va%/hpf or CD31 MVD of less than 35 Va%/hpf had a significantly better prognosis (no deaths during follow-up in the case of CD105) than did patients with higher scores of CD105 MVD (median survival, 35 mo; P = 0.041, n = 13) or CD31 MVD (median survival, 28 mo; P = 0.014, n = 13). Conclusion: Previous work has used [18F]FDG uptake in PET/CT as a biomarker in fILD. Here, we highlight a correlation between angiogenesis and [18F]FDG TBR. We show that MVD is higher for UIP than for non-UIP and is associated with mortality in patients with fILD. These data set the scene to investigate the potential role of vasculature and angiogenesis in fibrosis.

Complete separation of benzene-cyclohexene-cyclohexane mixtures via temperature-dependent molecular sieving by a flexible chain-like coordination polymer

The separation and purification of C6 cyclic hydrocarbons (benzene, cyclohexene, cyclohexane) represent a critically important but energy intensive process. Developing adsorptive separation technique to replace thermally driven distillation processes holds great promise to significantly reduce energy consumption. Here we report a flexible one-dimensional coordination polymer as an efficient adsorbent to discriminate ternary C6 cyclic hydrocarbons via an ideal molecular sieving mechanism. The compound undergoes fully reversible structural transformation associated with removal/re-coordination of water molecules and between activated and hydrocarbon-loaded forms. It exhibits distinct temperature- and adsorbate-dependent adsorption behavior which facilitates the complete separation of benzene, cyclohexene and cyclohexane from their binary and ternary mixtures, with the record-high uptake ratios for C6H6/C6H12 and C6H10/C6H12 in vapor phase and highest binary and ternary selectivities in liquid phase. In situ infrared spectroscopic analysis and ab initio calculations provide insight into the host-guest interactions and their effect on the preferential adsorption and structural transformation.

Assessment of DNA/RNA Deregulation in Cancer Using 99mTc-Labeled Thiopurine.

Background: DNA biomarkers are useful for the assessment of tumor cell proliferation. The authors aimed to synthesize a thiopurine-based ligand for evaluation of nuclear uptake and tumor localization. Materials and Methods: A 2-hydroxypropyl spacer was incorporated between a chelator (cyclam) and thiopurine ligand to produce SC-06-L1. In vitro cellular uptake and the cell/media ratios of [99mTc]Tc-SC-06-L1 were assessed in breast (MCF-7, MDA-MB-231) and ovarian (TOV-112D, OVCAR3) cancer cells. The nuclear and cytosolic uptake ratio of [99mTc]Tc-SC-06-L1 was determined in OVCAR-3 and MCF-7 cells. Cytotoxicity assays and flow cytometric analysis of cell cycle apoptosis were conducted in cancer cells treated with SC-06-L1. Imaging was conducted in tumor-bearing mice; fluorine-18-2'-fluorodeoxyglucose ([18F]FDG) was used as a control. Results: The radiochemical purity of [99mTc]Tc-SC-06-L1 was >95%. [99mTc]Tc-SC-06-L1 exhibited higher cell-to-media ratios than [18F]FDG in cancer cells. [99mTc]Tc-SC-06-L1 had high uptake in the nuclear fractions in OVCAR-3 and MCF-7 cells, with nuclear/cytosolic ratios of 8 and 2, respectively. Cytotoxicity assays showed that SC-06-L1 was non-toxic compared with azathioprine in breast and ovarian cancer cells. Conclusions: [99mTc]Tc-SC-06-L1 was stable and involved in nuclear activities. [99mTc]Tc-SC-06-L1 showed non-toxic to cancer cells and exhibited fast kinetic uptake patterns for tumor imaging. [99mTc]Tc-SC-06-L1 represents a promising biomarker for imaging purine pathway-directed systems.

Dissolved zinc in the western Bering Sea and near Kamchatka Strait: A coastal source and transport to the subarctic Pacific

Dissolved zinc (dZn) is an important micronutrient for phytoplankton in the ocean. In high nutrient low chlorophyll (HNLC) regions like the western Bering Sea basin, Zn deficiency might induce shifts in phytoplankton community species. In this study, we presented the first dZn distribution data in the western Bering Sea and near Kamchatka Strait and investigated the biogeochemical cycles of Zn in these regions. Although dZn and silicate (Si) show similar distribution patterns in the global ocean, there is an excess of dZn relative to Si in the intermediate waters of our study region, similar to that previously observed in the subarctic Pacific. The uptake and subsequent regeneration patterns of dZn, Si, and phosphate (PO4) in the study region reveal that excess dZn in the subarctic Pacific is not derived from biogenic processes, because the uptake and regeneration ratios of dZn to phosphate (PO4) cannot account for the additional dZn supplied. Instead, our analyses indicate that a significant proportion of dZn in the region originates from the non-reductive release from shelf sediments. dZn concentrations were elevated in coastal regions at the same isopycnal where excess dZn was observed in the subarctic Pacific, suggesting that some of these sediment-derived dZn were transported to the subarctic Pacific.

New Multi-Parameters Combination of Technetium-99m-Diethylene-Triamine-Pentaacetate Orbital Single-Photon Emission Computed Tomography/Computed Tomography for the Evaluation of Graves’ Orbitopathy Activity

ABSTRACT Purpose This study investigates the new combined parameters of 99mTc-DTPA orbital single-photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of Graves’ orbitopathy (GO) activity. Methods A retrospective analysis was performed on 41 patients. All the patients undergone the 99mTc-DTPA orbital SPECT/CT and were categorized into active and inactive group based on the standard combined by the clinical active score (CAS), magnet resonance imaging (MRI) and/or follow-up results. Quantitative parameters of lacrimal gland (LG) including the protruding degree of lacrimal gland herniation (LGH) and uptake ratios (URs) of region of interest (ROI) drawn on lacrimal gland and occipital bone. SPECT/CT reading results were based on visual analysis. Parameters were compared between the two groups and the diagnostic value on discrimination of GO activity was also evaluated. Results All parameters of SPECT/CT for active GO groups were significantly higher than those of the inactive groups (p<.05). There were notable linear positive correlations between the assumption standard and readings as well as combination models 2 and 3 (r = .794, r = .772, r = .760, respectively). ROC analysis indicated that model 2 provided the highest diagnostic performance, exhibiting an area under the curve (AUC) of .947, a sensitivity of 92.7%, and a specificity of 88.6%. Conclusions The combined use of SPECT/CT reading results and DTPA uptake parameters of LG offers a more objective and precise evaluation of active GO. This study further recommends 99mTc-DTPA SPECT/CT might be serving as a supplementary beneficial approach for CAS in evaluating GO activity.

Analyzing the value of delayed 18 F-FDG PET/CT images in diagnosing small colorectal cancer liver metastases in patients with hypothyroidism based on diagnostic accuracy and image standardized uptake value.

The objective of this study was to investigate the value of delayed 18F fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) images in patients with small colorectal cancer liver metastases (CRLMs) with hypothyroidism. We performed a retrospective analysis of 66 small-CRLM patients with hypothyroidism and 66 small-CRLM patients with euthyroidism, all of whom underwent dual-time-point 18 F-FDG PET/CT imaging. First, the diagnostic accuracy of PET/CT early imaging and PET/CT delayed imaging on lesions was analyzed. Next, the correlation of metabolic parameters between PET/CT early imaging and PET/CT delayed imaging was analyzed according to the grouping of all lesions. Finally, PET/CT parameters were analyzed for correlation with thyroid hormones. The diagnostic accuracy of delayed imaging in small-CRLM patients with hypothyroidism is not as good as that in small-CRLM patients with euthyroidism; PET/CT metabolic parameters are also unfavorable for the diagnosis of small-CRLM. For small-CRLM patients with hypothyroidism, the greater the thyroid-stimulating hormone level, the greater the uptake of 18 F-FDG in normal liver tissue, and the smaller the ratio of tumor lesion uptake to normal liver tissue uptake. PET/CT-delayed imaging has better performance than early imaging in small-CRLM patients with euthyroidism. However, the more severe the hypothyroidism, the worse the diagnostic delayed imaging performance. The scan time can be extended appropriately to optimize the imaging efficacy.

Adsorptive separation of Xe/Kr mixtures by microporous lanthanide metal-organic frameworks with high thermal stability

Efficient separation of Xenon (Xe) and Krypton (Kr) is a significant process for their wide industrial applications and potential environmental concerns. Owing to the inert atomic gases (Xe and Kr) nature with similar physical and chemical properties, it is a great challenge to achieve efficient separation of the Xe/Kr mixture. Herein, we report a series of microporous lanthanide based metal-organic frameworks Ln (BTC) (H2O)·(DMF)1.1 (Ln-MOF) (Dy-BTC (1), Er-BTC (2), and Yb-BTC (3)) with ultrahigh thermal stability for adsorptive Xe/Kr separation. These three isostructural Ln-MOFs consisted of lanthanide metal ions and 1,3,5-benzene dicarboxylate ligands that possess a square channel with pore sizes of 6–7 Å. By substitution of Ln ions, Yb-BTC shows the smallest pore size among the three compounds which enables its obvious higher Xe/Kr selectivity compared with the other two Ln-MOFs. Yb-BTC exhibits a moderately high Xe uptake of 2.5 mmol/g (298 K and 1 bar), and a significantly high Xe/Kr uptake ratio of 3.8, indicative of its great potential for separation of Xe/Kr mixture. The effective Xe/Kr separation ability of Yb-BTC was also confirmed by a breakthrough experiment.

High Diagnostic Accuracy of Thyroid-Stimulating Hormone (TSH) Receptor Antibodies in Distinguishing Graves' Disease and Subacute Thyrotoxicosis in the Indian Population.

Thyrotoxicosis is a common clinical condition encountered in endocrine practice. Graves' disease and subacute thyroiditis are the two common causes of thyrotoxicosis and often have overlapping clinical and biochemical features. 99mTc thyroid scintigraphy is the most commonly used confirmatory test to differentiate the two conditions but is not available in the majority of the second-tier cities of India. However, obtaining thyroid stimulating hormone (TSH) receptor antibodies (TSHrAb), another accurate test to differentiate the two conditions, in second-tier cities by outsourcing to labs in major cities is a feasible option nowadays. However, the data on the performance of TSHrAb to differentiate the two conditions in Indian patients is limited. Hence, we have evaluated the diagnostic accuracy of TSHrAb in the Indian population to differentiate Graves' disease and subacute thyroiditis. This prospective studywas conducted on 115 consecutive newly diagnosed thyrotoxicosis patients presenting to the Department of Endocrinology at a tertiary health care centre in India. Clinical parameters like throat pain, duration of symptoms, and grade of goitre were noted. Measurement of total tri-iodothyronine (TT3), total thyroxine (TT4), TSH, TSHrAb, and 99mTc thyroid scintigraphy were performed in all participants. All participants were followed up at least for six months after the recruitment. Increased tracer uptake (>4%) and/or increased thyroid to parotid trace uptake ratio (>2.5) were used to diagnose Graves' disease. Eighty-one and 34 patients were diagnosed with Graves' disease and subacute thyroiditis, respectively. TT3/TT4 ratio had low diagnostic accuracy (area under the curve (AUC): 0.6, best cut-off: 15.6, sensitivity: 53.1%, specificity: 79.4%). TSHrAb had the best AUC (0.9) to distinguish Graves' disease from subacute thyroiditis (cut-off: 2.0 IU/L, sensitivity: 97.5%, specificity: 100%). In contrast, the kit manufacturer's reference range (1.75 IU/L) was slightly more sensitive (98.8%), but less specific (94%). The TT3/TT4 ratio is not a good test to differentiate Graves' disease and subacute thyroiditis. TSHrAb is accurate in distinguishing Graves' disease from subacute thyroiditis and a level of 2.0 may be a more accurate cut-off to differentiate the two conditions in the Indian population.

Effect of Cyclosporin H on ischemic injury and neutrophil infiltration in cerebral infarct model of rats via PET imaging.

Brain ischemia-reperfusion injury is a complex process, and neuroinflammation is an important secondary contributing pathological event. Neutrophils play major roles in ischemic neuroinflammation. Once activated, neutrophils express formyl peptide receptors (FPRs), which are special receptors of a class of chemoattractants and may be potential targets to regulate the activity of neutrophils and control cerebral ischemic injury. This study was aimed to explore the ameliorating effect of Cyclosporin H (CsH), a potent FPR antagonist, on brain ischemic injury by inhibiting the activation and migration of neutrophils, and improving cerebral blood flow. We employed a middle cerebral artery occlusion (MCAO) Model on rats and performed behavioral, morphological, and microPET imaging assays to investigate the potential restoring efficacy of CsH on cerebral ischemic damages. Peptide N-cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), an antagonist to the neutrophil FPR with a high binding affinity, was used for imaging neutrophil distribution. We found that CsH had similar effect with edaravone on improving the neurobehavioral deficient symptoms after cerebral ischemia-reperfusion, and treatment with CsH also alleviated ischemic cerebral infarction. Compared with the MCAO Model group, [18F]FDG uptake ratios of the CsH and edaravone treatment groups were significantly higher. The CsH-treated groups also showed significant increases in [18F]FDG uptake at 144h when compared with that of 24h. This result indicates that like edaravone, treatment with both doses of CsH promoted the recovery of blood supply after cerebral ischemic event. Moreover, MCAO-induced cerebral ischemia significantly increased the radiouptake of [68Ga]Ga-cFLFLF at 72h after ischemia-reperfusion operation. Compared with MCAO Model group, radiouptake values of [68Ga]-cFLFLF in both doses of CsH and edaravone groups were all decreased significantly. These results showed that both doses of CsH resulted in a similar therapeutic effect with edaravone on inhibiting neutrophil infiltration in cerebral infarction. Potent FPR antagonist CsH is promisingly beneficial in attenuating neuroinflammation and improving neurobehavioral function against cerebral infarction. Therefore, FPR may become a novel target for regulating neuroinflammation and improving prognosis for ischemic cerebrovascular disorders.

Development, preclinical evaluation and preliminary dosimetry profiling of SB03178, a first-of-its-kind benzo[h]quinoline-based fibroblast activation protein-α-targeted radiotheranostic for cancer imaging and therapy

Fibroblast activation protein-α (FAP) is a marker of cancer-associated fibroblasts (CAFs) that constitute a significant portion of most carcinomas. Since it plays a critical role in tumor growth and metastasis, its timely detection to identify tumor lesions in early developmental stages using targeted radiopharmaceuticals has gained significant impetus. In the present work, two novel FAP-targeted precursors SB03178 and SB04033 comprising of an atypical benzo[h]quinoline construct were synthesized and either chelated to diagnostic radionuclide gallium-68 or therapeutic radionuclide lutetium-177, with ≥90% radiochemical purities and 22–76% decay-corrected radiochemical yields. natGa-labeled complexes displayed dose-dependent FAP inhibition, with binding potency of natGa-SB03178 being ∼17 times higher than natGa-SB04033. To evaluate their pharmacokinetic profiles, PET imaging and ex vivo biodistribution analyses were executed in FAP-overexpressing HEK293T:hFAP tumor-bearing mice. While both tracers displayed clear tumor visualization that was primarily FAP-arbitrated, with negligible uptake in most peripheral tissues, [68Ga]Ga-SB03178 demonstrated higher tumor uptake and superior tumor-to-background contrast ratios than [68Ga]Ga-SB04033. 177Lu-labeled SB03178 was subjected to tumor retention studies, mouse dosimetry profiling and mouse-to-human dose extrapolations also using the HEK293T:hFAP tumor model. [177Lu]Lu-SB03178 exhibited a combination of high and sustained tumor uptake, with excellent tumor-to-critical organ uptake ratios resulting in a high radiation absorbed dose to the tumor and a low estimated whole-body dose to humans. Our preliminary findings are considerably encouraging to support clinical development of [68Ga]Ga-/[177Lu]Lu-SB03178 theranostic pair for use in a vast majority of FAP-overexpressing neoplasms, particularly carcinomas.

Pengaruh Pupuk Hayati Jamur Mikoriza Dan Pupuk Rock Phosphate Terhadap Serapan P, Pertumbuhan serta Hasil Tanaman Cabai Rawit (Capsicum frutescens L.)

Application of mycorrhizal fungi biological fertilizers and rock phosphate fertilizers can increase plant P uptake, growth and yield of cayenne pepper (Capsicum frutescens L.). The purpose of this study was to determine the effect of the interaction between mycorrhizal fungi biofertilizer and rock phosphate fertilizer on P uptake, growth and yield of cayenne pepper. The experimental design used was a completely randomized design (CRD) factorial with 2 factors and 3 replications. The first factor was the application of 0 gr (M0), 10 g (M1) and 20 g (M2) mycorrhizal fungal biofertilizers and the second factor was the application of 0 kg rock phosphate fertilizer or the equivalent of 0 g (R0), 150 kg or 1 g (R1) and 300 kg or 2.6 g (M2). The variables observed were plant height, number of fruit planted, fruit fresh weight, plant fresh weight, root volume, root infection, plant dry weight, root shoot ratio and P uptake. The observed data were tested using analysis of variance (ANOVA) and tested further. using Duncan multiple range test (DMRT) at 95% confidence level. The results showed that there was no interaction between the application of mycorrhizal fungi biofertilizers and rock phosphate fertilizers. Application of mycorrhizal fungal biofertilizer (M1) can increase the degree of root infection by 72.22%, the number of fruit planted, fruit fresh weight, plant fresh weight, plant dry weight, root volume, root infection, P uptake and root shoot ratio. Application of rock phosphate fertilizer can also increase the number of fruit plants, plant fresh weight, plant dry weight, root volume and P uptake.&#x0D;

Preclinical evaluation of 68Ga-labeled peptide CK2 for PET imaging of NRP-1 expression in vivo.

Neuropilin-1 (NRP-1) is a multifunctional protein involved in a variety of biological processes such as angiogenesis, tumorigenesis and immunomodulation. It was usually overexpressed in many cancer cell lines and correlated with poor prognosis of breast cancer. Positron emission tomography (PET) is an advanced imaging technique for detecting the function and metabolism of tumor-associated molecules in real time, dynamically, quantitatively and noninvasively. To improve the level of early diagnosis and evaluate the prognosis of breast cancer, an NRP-1 targeting peptide-based tracer [68Ga]Ga-NOTA-PEG4-CK2 was designed to sensitively and specifically detect the NRP-1 expression in vivo via PET imaging. In silico modeling and microscale thermophoresis (MST) assay were carried out to design the NRP-1 targeting peptide NOTA-PEG4-CK2, and it was further radiolabeled with 68Ga to prepare the tracer [68Ga]Ga-NOTA-PEG4-CK2. The radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), lipid-water partition coefficient (Log P) and stability of [68Ga]Ga-NOTA-PEG4-CK2 were assessed. The targeting specificity of the tracer for NRP-1 was investigated by in vitro cellular uptake assay and in vivo PET imaging as well as blocking studies. The sensitivity of the tracer in monitoring the dynamic changes of NRP-1 expression induced by chemical drug was also investigated in vitro and in vivo. Ex vivo biodistribution, autoradiography, western blot, and immunofluorescence staining were also performed to study the specificity of [68Ga]Ga-NOTA-PEG4-CK2 for NRP-1. [68Ga]Ga-NOTA-PEG4-CK2 was designed and synthesized with high RCY (> 98%), high stability (RCP > 95%) and high affinity to NRP-1 (KD = 25.39 ± 1.65nM). In vitro cellular uptake assay showed that the tracer [68Ga]Ga-NOTA-PEG4-CK2 can specifically bind to NRP-1 positive cancer cells MDA-MB-231 (1.04 ± 0.04% at 2h) rather than NRP-1 negative cancer cells NCI-H1299 (0.43 ± 0.05%). In vivo PET imaging showed the maximum tumor uptake of [68Ga]Ga-NOTA-PEG4-CK2 in MDA-MB-231 xenografts (4.16 ± 0.67%ID/mL) was significantly higher than that in NCI-H1299 xenografts (1.03 ± 0.19%ID/mL) at 10min post injection, and the former exhibited higher tumor-to-muscle uptake ratio (5.22 ± 0.18) than the latter (1.07 ± 0.27) at 60min post injection. MDA-MB-231 xenografts pretreated with nonradioactive precursor NOTA-PEG4-CK2 showed little tumor uptake of [68Ga]Ga-NOTA-PEG4-CK2 (1.67 ± 0.38%ID/mL at 10min post injection). Both cellular uptake assay and PET imaging revealed that NRP-1 expression in breast cancer MDA-MB-231 could be effectively suppressed by SB-203580 treatment and can be sensitively detected by [68Ga]Ga-NOTA-PEG4-CK2. Ex vivo analysis also proved the high specificity and sensitivity of [68Ga]Ga-NOTA-PEG4-CK2 for NRP-1 expression in MDA-MB-231 xenografts. A promising NRP-1 targeting PET tracer [68Ga]Ga-NOTA-PEG4-CK2 was successfully prepared. It showed remarkable specificity and sensitivity in monitoring the dynamic changes of NRP-1 expression. Hence, it could provide valuable information for early diagnosis of NRP-1 relevant cancers and evaluating the prognosis of cancer patients.

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol

IntroductionPositron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored....

Ethane/Ethylene Separations in Flexible Diamondoid Coordination Networks via an Ethane-Induced Gate-Opening Mechanism.

Separating ethane (C2H6) from ethylene (C2H4) is an essential and energy-intensive process in the chemical industry. Here, we report two flexible diamondoid coordination networks, X-dia-1-Ni and X-dia-1-Ni0.89Co0.11, that exhibit gate-opening between narrow-pore (NP) and large-pore (LP) phases for C2H6, but not for C2H4. X-dia-1-Ni0.89Co0.11 thereby exhibited a type F-IV isotherm at 273 K with no C2H6 uptake and a high uptake (111 cm3 g-1, 1 atm) for the NP and LP phases, respectively. Conversely, the LP phase exhibited a low uptake of C2H4 (12.2 cm3 g-1). This C2H6/C2H4 uptake ratio of 9.1 for X-dia-1-Ni0.89Co0.11 far surpassed those of previously reported physisorbents, many of which are C2H4-selective. In situ variable-pressure X-ray diffraction and modeling studies provided insight into the abrupt C2H6-induced structural NP to LP transformation. The promise of pure gas isotherms and, more generally, flexible coordination networks for gas separations was validated by dynamic breakthrough studies, which afforded high-purity (99.9%) C2H4 in one step.

A Pilot Study To Assess the Suitability of Riboflavin As a Surrogate Marker of Breast Cancer Resistance Protein in Healthy Participants.

We recently showed that riboflavin is a selected substrate of breast cancer resistance protein (BCRP) over P-glycoprotein (P-gp) and demonstrated its prediction performance in preclinical drug-drug interaction (DDI) studies. The aim of this study was to investigate the suitability of riboflavin to assess BCRP inhibition in humans. First, we assessed the substrate potential of riboflavin toward other major drug transporters using established transfected cell systems. Riboflavin is a substrate for organic anion transporter (OAT)1, OAT3, and multidrug and toxin extrusion protein (MATE)2-K, with uptake ratios ranging from 2.69 to 11.6, but riboflavin is not a substrate of organic anion-transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)2, and MATE1. The effects of BMS-986371, a potent in vitro inhibitor of BCRP (IC 50 0.40 μM), on the pharmacokinetics of riboflavin, isobutyryl carnitine, and arginine were then examined in healthy male adults (N = 14 or 16) after oral administration of methotrexate (MTX) (7.5 mg) and enteric-coated (EC) sulfasalazine (SSZ) (1000 mg) alone or in combination with BMS-986371 (150 mg). Oral administration of BMS-986371 increased the area under the plasma concentration-time curves (AUCs) of rosuvastatin and immediate-release (IR) SSZ to 1.38- and 1.51-fold, respectively, and significantly increased AUC(0-4h), AUC(0-24h), and C max of riboflavin by 1.25-, 1.14-, and 1.11-fold (P-values of 0.003, 0.009, and 0.025, respectively) compared with the MTX/SSZ EC alone group. In contrast, BMS-986371 did not significantly influence the AUC(0-24h) and C max values of isobutyryl carnitine and arginine (0.96- to 1.07-fold, respectively; P > 0.05). Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development. SIGNIFICANCE STATEMENT: Endogenous compounds that serve as biomarkers for clinical inhibition of breast cancer resistance protein (BCRP) are not currently available. This study provides the initial evidence that riboflavin is a promising BCRP biomarker in humans. For the first time, the value of leveraging the substrate of BCRP with acceptable prediction performance in clinical studies is shown. Additional clinical investigations with known BCRP inhibitors are needed to fully validate and showcase the utility of this biomarker.

Below or all the way to the peak? Oxygen uptake efficiency slope as the index of cardiorespiratory response to exercise-the NOODLE study.

Background: The ratio of oxygen uptake (VO2) to minute ventilation (VE) is described as the oxygen uptake efficiency slope (OUES). OUES has been suggested as a valuable submaximal cardiorespiratory index; however, its characteristics in endurance athletes remain unknown. In this study, we a) investigated OUES between different time intervals, b) assessed their prediction power for VO2peak, and c) derived new prediction equations for OUES tailored for well-trained individuals. Materials and Methods: A total of 77 male (age = 21.4 ± 4.8yrs; BMI = 22.1 ± 1.6kg·m-2; peak oxygen uptake = 4.40 ± 0.64L·min-1) and 63 female individuals (age = 23.4 ± 4.3yrs; BMI = 23.1 ± 1.6kg·m-2; peak oxygen uptake = 3.21 ± 0.48L·min-1) underwent the cycling cardiopulmonary exercise test. OUES was measured at 75%, 90%, and 100% of exercise duration. Prediction power and new models were derived with the multiple linear regression method. Results: In male subjects, OUES [mL·min-1/L·min-1] from 75% = 4.53 ± 0.90, from 90% = 4.52 ± 0.91, and from 100% = 4.41 ± 0.87. In female subjects, OUES [mL·min-1/L·min-1] from 75% = 3.50 ± 0.65, from 90% = 3.49 ± 0.62, and from 100% = 3.41 ± 0.58. OUES did not differ between time intervals in male (p = 0.65) and female individuals (p = 0.69). OUES strongly predicts peak VO2 independently from the measuring interval (β = 0.71-0.80; R 2 = 0.50-0.63). The prediction model designed for elite athletes was OUES [mL·min-1/L·min-1] = -1.54 + 2.99; BSA [m2]-0.0014; (age [in years]; sex [1 = male, 2 = female]) (R 2 = 0.36). Conclusion: OUES enables an accurate prediction of peak cardiorespiratory fitness in elite endurance athletes. OUES is a feasible alternative to maximal exercise testing. A new prediction equation should be used for highly trained individuals. Physicians should understand OUES physiology to properly assess the cardiorespiratory response to exercise in athletic cohorts.

Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.