Clinical and Neuroimaging Predictors of Alzheimer's Dementia Conversion in Patients with Mild Cognitive Impairment Using Amyloid Positron Emission Tomography by Quantitative Analysis over 2 Years.

Patients with mild cognitive impairment (MCI) have a relatively high risk of developing Alzheimer's dementia (AD), so early identification of the risk for AD conversion can lessen the socioeconomic burden. In this study, 18F-Florapronol, newly developed in Korea, was used for qualitative and quantitative analyses to assess amyloid positivity. We also investigated the clinical predictors of the progression from MCI to dementia over 2 years. From December 2019 to December 2022, 50 patients with MCI were recruited at a single center, and 34 patients were included finally. Based on visual analysis, 13 (38.2%) of 34 participants were amyloid-positive, and 12 (35.3%) were positive by quantitative analysis. Moreover, 6 of 34 participants (17.6%) converted to dementia after a 2-year follow-up (p = 0.173). Among the 15 participants who were positive for amyloid in the posterior cingulate region, 5 (33.3%) patients developed dementia (p = 0.066). The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) at baseline was significantly associated with AD conversion in multivariate Cox regression analyses (p = 0.043). In conclusion, these results suggest that amyloid positivity in the posterior cingulate region and higher CDR-SOB scores at baseline can be useful predictors of AD conversion in patients with MCI.

Geraniin Alleviates Inflammation in Caco-2 Cells and Dextran Sulfate Sodium-Induced Colitis Mice by Targeting IL-1ß.

IL-1ß is an important cytokine implicated in the progression of inflammatory bowel disease (IBD) and intestinal barrier dysfunction. The polyphenolic compound, geraniin, possesses bioactive properties, such as antitumor, antioxidant, anti-inflammatory, antihypertensive, and antiviral activities; however, its IL-1ß-targeted anticolitis activity remains unclear. Here, we evaluated the inhibitory effect of geraniin in IL-1ß-stimulated Caco-2 cells and a dextran sulfate sodium (DSS)-induced colitis mouse model. Geraniin blocked the interaction between IL-1ß and IL-1R by directly binding to IL-1ß and inhibited the IL-1ß activity. It suppressed IL-1ß-induced intestinal tight junction damage in human Caco-2 cells by inhibiting IL-1ß-mediated MAPK, NF-kB, and MLC activation. Moreover, geraniin administration effectively reduced colitis symptoms and attenuated intestinal barrier injury in mice by suppressing elevated intestinal permeability and restoring tight junction protein expression through the inhibition of MAPK, NF-kB, and MLC activation. Thus, geraniin exhibits anti-IL-1ß activity and anticolitis effect by hindering the IL-1ß and IL-1R interaction and may be a promising therapeutic anti-IL-1ß agent for IBD treatment.

Celastrol, which targets IL-2/CD25 binding inhibition, induces T cell-mediated antitumor activity in melanoma.

Interleukin-2 (IL-2) induces contrasting immune responses depending on its binding receptor subunit; thus, selective receptor binding is considered a key challenge in cancer therapeutic strategies. In this study, we aimed to investigate the inhibition of IL-2 action and antitumor activity of celastrol (CEL), a compound identified in a screen for IL-2/CD25 binding inhibitors, and to elucidate the underlying role of CEL in immune cells. We found that CEL selectively impairs the binding of IL-2 and CD25 and directly binds to IL-2 but not to CD25. CEL significantly suppressed the proliferation and signaling of IL-2-dependent murine T cells and interfered with IL-2-responsive STAT5 phosphorylation in IL-2 reporter cells and human PBMCs. After confirming the impact of CEL on IL-2, we evaluated its antitumor activity in C57BL/6 mice bearing B16F10 tumors and found that CEL significantly inhibited tumor growth by increasing CD8+ T cells. We also found that CEL did not inhibit tumor growth in T cell-deficient BALB/c nude mice, suggesting that its activity was mediated by the T-cell response. Moreover, combination therapy with low-dose CEL and a TNFR2 antagonist synergistically improved the therapeutic efficacy of the individual monotherapies by increasing the ratio of intratumoral CD8/Treg cells and suppressing Foxp3 expression. These findings suggest that CEL, which inhibits CD25 binding by targeting IL-2, exerts antitumor activity by mediating the T-cell response and could be a promising candidate for combination therapy in cancer immunotherapy against melanoma.

Tannic acid, an IL-1ß-direct binding compound, ameliorates IL-1ß-induced inflammation and cartilage degradation by hindering IL-1ß-IL-1R1 interaction.

Interleukin-1ß (IL-1ß) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1ß-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1ß activity by blocking IL-1ß-IL-1R1 interaction in OA. In this study, we report the anti-IL-1ß activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1ß-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1ß-IL-1R1 interaction by direct binding to IL-1ß using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1ß bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1ß-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1ß-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1ß-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1ß-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1ß-related diseases by hindering IL-1ß-IL-1R1 interaction and suppressing IL-1ß bioactivity.

Chelerythrine, a novel small molecule targeting IL-2, inhibits melanoma progression by blocking the interaction between IL-2 and its receptor.

AIMS: In this study, we investigated the inhibition of IL-2 activity and anticancer efficacy of chelerythrine (CHE), a natural small molecule that targets IL-2 and inhibits CD25 binding, and elucidated the mechanism underlying the action of CHE on immune cells. MAIN METHODS: CHE was discovered by competitive binding ELISA and SPR analysis. The effect of CHE on IL-2 activity was evaluated in CTLL-2, HEK-Blue reporter and immune cells, and in ex vivo generation of regulatory T cells (Treg cells). The antitumor activity of CHE was evaluated in B16F10 tumor-bearing C57BL/6 or BALB/c nude mice. KEY FINDINGS: We identified that CHE, which acts as an IL-2 inhibitor, selectively inhibits the interaction between IL-2 and IL-2Rα and directly binds to IL-2. CHE inhibited the proliferation and signaling of CTLL-2 cells and suppressed IL-2 activity in HEK-Blue reporter and immune cells. CHE prevented the conversion of naive CD4+ T cells into CD4+CD25+Foxp3+ Treg cells in response to IL-2. CHE reduced tumor growth in C57BL/6 mice but not in T-cell-deficient mice, upregulated the expression of IFN-γ and cytotoxic molecules, and limited Foxp3 expression. Furthermore, the combination of CHE and a PD-1 inhibitor synergistically increased antitumor activity in melanoma-bearing mice and almost completely regressed the implanted tumors. SIGNIFICANCE: We found that CHE, which targets IL-2 and inhibits its binding to CD25, exhibits T cell-mediated antitumor activity and that combination therapy with CHE and PD-1 inhibitor induced synergistic antitumor effects, suggesting that CHE may be a promising anticancer agent for melanoma monotherapy and combination therapy.

Quantitative comparative analysis of amyloid PET images using three radiopharmaceuticals.

OBJECTIVE: Amyloid positron emission tomography (PET) with F-18 florbetaben (FBB), F-18 flutemetamol (FMM), and F-18 florapronol (FPN) is being used clinically for the evaluation of dementia. These radiopharmaceuticals are commonly used to evaluate the accumulation of beta-amyloid plaques in the brain, but there are structural differences between them. We investigated whether there are any differences in the imaging characteristics. METHODS: A total of 605 subjects were enrolled retrospectively in this study, including healthy subjects (HS) and patients with mild cognitive impairment or Alzheimer's disease. Participants underwent amyloid PET imaging using one of the three radiopharmaceuticals. The PET images were analyzed visually and semi-quantitatively using a standardized uptake value ratio (SUVR). In addition, we calculated and compared the cut-off SUVR of the representative regions for each radiopharmaceutical that can distinguish between positive and negative scans. RESULTS: In the negative images of the HS group, the contrast between the white matter and the gray matter was high in the FMM PET images, while striatal uptake was relatively higher in the FPN PET images. The SUVR showed significant differences across the radiopharmaceuticals in all areas except the temporal lobe, but the range of differences was relatively small. Accuracy levels for the global cut-off SUVR to discriminate between positive and negative images were highest in FMM PET, with a value of 0.989. FBB PET also showed a high value of 0.978, while FPN PET showed a relatively low value of 0.901. CONCLUSIONS: Negative amyloid PET images using the three radiopharmaceuticals showed visually and quantitatively similar imaging characteristics except in the striatum. Binary classification using the cut-off of the global cortex showed high accuracy overall, although there were some differences between the three PET images.

KSNM60 in Nuclear Endocrinology: from the Beginning to the Future.

Nuclear endocrinology is the main ignitor for founding the Korean Society of Nuclear Medicine (KSNM) in the early 1960s by outstanding pioneering medical doctors. Management of thyroid diseases required nuclear medicine technology in the early days of the KSNM and was rapidly developed by advancements in nuclear medicine technology. Nuclear thyroidology remains one of the main clinical applications in nuclear medicine worldwide. Nuclear medicine technology provides essential information for diagnosing and assessing diseases of the parathyroid glands, pituitary gland, and neuroendocrine tumors (NETs). In addition, therapeutic nuclear medicine is essential for managing nonresectable NETs. Nuclear endocrinology remains a major section in clinical nuclear medicine, and members of the KSNM have contributed to progressing better management of benign and malignant endocrine diseases. This review summarizes the historical activities and milestone contributions to nuclear endocrinology made by the members of the KSNM over the past 60 years to congratulate the KSNM on its 60-year anniversary.

Discovery of Mycobacterium tuberculosis Rv3364c-Derived Small Molecules as Potential Therapeutic Agents to Target SNX9 for Sepsis.

The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the 12WLVSKF17 motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficking to interact with p47phox, thereby suppressing TLR4 inflammatory signaling in macrophages. Derived from the structure of this Rv3364c peptide motif, 2,4-diamino-6-(4-tert-butylphenyl)-1,3,5-trazine, DATPT as a 12WLVSKF17 peptide-mimetic small molecule has been identified. DATPT can block the SNX9-p47phox interaction in the endosome and suppress reactive oxygen species and inflammatory cytokine production; it demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis. DATPT has considerably improved potency, with an IC50 500-fold (in vitro) or 2000-fold (in vivo) lower than that of the 12WLVSKF17 peptide. Furthermore, DATPT shows potent antibacterial activities by reduction in ATP production and leakage of intracellular ATP out of bacteria. These results provide evidence for peptide-derived small molecule DATPT with anti-inflammatory and antibacterial functions for the treatment of sepsis.

Atypical sarcoid reaction mimicking recurrence on F-18 FDG PET/CT in a patient with breast malignancy.

Malignancy may lead to sarcoidosis, which is referred to as sarcoid reaction. This reaction is believed to be a host immune response to the release of soluble antigens from cancer cells. Studies have shown strong 2'-deoxy-2'-[F-18]fluoro-D-glucose (F-18 FDG) uptake in sarcoid reaction and in true sarcoidosis. Therefore, in patients with malignancy, sarcoid reactions can mimic metastasis or recurrence on F-18 FDG positron emission tomography/computed tomography (PET/CT). Herein, we report the case of a 58-year-old woman with a history of left breast cancer whose FDG PET/CT evaluated at 3 months after adjuvant chemotherapy presented hypermetabolic lymphadenopathy in the right supraclavicular and right mediastinal areas. We interpreted these as metastases because the involved lymph nodes were intensely hypermetabolic and appeared newly. Pathologic evaluation of the excised lymph node revealed noncaseating chronic granulomas without malignant cells, indicating a sarcoid reaction. After appropriate steroid therapy, both the size and metabolic activity of the lymphadenopathy substantially decreased. Most sarcoid reactions present as bilateral hilar and peribronchial lymphadenopathies. Our patient presents an atypical example that a sarcoid reaction can also present in a unilateral pattern, making its diagnosis challenging. When interpreting FDG PET/CT images, considering that the sarcoid reaction pattern can vary is crucial.

Heterogeneity by global and textural feature analysis in F-18 FP-CIT brain PET images for diagnosis of Parkinson's disease.

BACKGROUND: The quantification of heterogeneity for the striatum and whole brain with F-18 FP-CIT PET images will be useful for diagnosis. The index obtained from texture analysis on PET images is related to pathological change that the neuronal loss of the nigrostriatal tract is heterogeneous according to the disease state. The aim of this study is to evaluate various heterogeneity indices of F-18 FP-CIT PET images in the diagnosis of Parkinson's disease (PD) patients and to access the diagnostic accuracy of the indices using machine learning (ML). METHODS: This retrospective study included F-18 FP-CIT PET images of 31 PD and 31 age-matched health controls (HC). The volume of interest was delineated according to iso-contour lines around standardized uptake value (SUV) 3.0 g/ml for each region of the striatum by PMod 3.603. One hundred eight heterogeneity indices were calculated using CGITA to find indices from which the PD and HC were classified using statistical significance. PD group was classified by constructing a 2-dimensional or 3-dimensional phase space quantifier using these heterogeneity indices. We used 71 heterogeneity indices to classify PD from HC using ML for dimensional reduction. RESULTS: The heterogeneity indices for classifying PD from HC were size-zone variability, contrast, inverse difference-moment, and homogeneity in the order of low P value. Three-dimensional quantifiers composed of normalized-contrast, code-similarity, and contrast were more clearly classified than 2-dimensional ones. After 71-dimensional reduction using PCA, classification was possible by logistic regression with 91.3% accuracy. The 2 groups were classified with an accuracy of 85.5% using the support vector machine and 88.4% using the random forest. The classification accuracy using the eXtreme Gradient Boosting was 95.7%, and feature importance was highest in order of SUV bias-corrected kurtosis, size-zone-variability, intensity-variability, and high-intensity-zone-variability. CONCLUSION: It was confirmed that PD patients is more clearly classified than the conventional 2-dimensional quantifier by introducing a 3-dimensional phase space quantifier. We observed that ML can be used to classify the 2 groups in an easy and explanatory manner. For the discrimination of the disease, 24 heterogeneity indices were found to be statistically useful, and the major cut-off values of 3 heterogeneity indices were size-zone variability (1906.44), intensity variability (129.21), and high intensity zone emphasis (800.29).

Multi-Functional MPT Protein as a Therapeutic Agent against Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), avoids the host immune system through its virulence factors. MPT63 and MPT64 are the virulence factors secreted by MTB which regulate host proteins for the survival and proliferation of MTB in the host. Here, we found that MPT63 bound directly with TBK1 and p47phox, whereas MPT64 interacted with TBK1 and HK2. We constructed a MPT63/64-derived multifunctional recombinant protein (rMPT) that was able to interact with TBK1, p47phox, or HK2. rMPT was shown to regulate IFN-ß levels and increase inflammation and concentration of reactive oxygen species (ROS), while targeting macrophages and killing MTB, both in vitro and in vivo. Furthermore, the identification of the role of rMPT against MTB was achieved via vaccination in a mouse model. Taken together, we here present rMPT, which, by regulating important immune signaling systems, can be considered an effective vaccine or therapeutic agent against MTB.

Restoration of amyloid PET images obtained with short-time data using a generative adversarial networks framework.

Our purpose in this study is to evaluate the clinical feasibility of deep-learning techniques for F-18 florbetaben (FBB) positron emission tomography (PET) image reconstruction using data acquired in a short time. We reconstructed raw FBB PET data of 294 patients acquired for 20 and 2 min into standard-time scanning PET (PET20m) and short-time scanning PET (PET2m) images. We generated a standard-time scanning PET-like image (sPET20m) from a PET2m image using a deep-learning network. We did qualitative and quantitative analyses to assess whether the sPET20m images were available for clinical applications. In our internal validation, sPET20m images showed substantial improvement on all quality metrics compared with the PET2m images. There was a small mean difference between the standardized uptake value ratios of sPET20m and PET20m images. A Turing test showed that the physician could not distinguish well between generated PET images and real PET images. Three nuclear medicine physicians could interpret the generated PET image and showed high accuracy and agreement. We obtained similar quantitative results by means of temporal and external validations. We can generate interpretable PET images from low-quality PET images because of the short scanning time using deep-learning techniques. Although more clinical validation is needed, we confirmed the possibility that short-scanning protocols with a deep-learning technique can be used for clinical applications.

Osteosarcoma of talus with heterotopic ossifications and lung metastases.

Osteosarcoma is the most common malignant bone tumor and is known to occur mainly in the metaphyses of long bones. However, a few cases of osteosarcoma in talus have been reported in older patients. We experienced an osteosarcoma of an 80-year-old male patient with a talus which is rarely reported and evaluated disease patterns with four different imaging modalities.

Relationship between the washout rate of I-123 MIBG scans and autonomic function in Parkinson's disease.

PURPOSE: We have evaluated the clinical significance of the washout rate (WR) on I-123 MIBG scans through the analysis of the relationship between the I-123 MIBG scans and autonomic status in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Sixty patients with clinical PD who had decreased HMR were enrolled. An autonomic symptom was evaluated using a head-up tilt test and the Composite Autonomic Severity Score (CASS). An I-123 MIBG scan and F-18 FP-CIT positron emission tomography (PET) were performed. All of the patients were classified into three groups according to the WR. The differences in patient characteristics and the imaging parameters among the three groups were evaluated, and a correlation analysis was also performed. RESULTS: The frequency of orthostatic hypotension was significantly different among the three groups. The difference in systolic pressure (dSysPr) and the difference in diastolic pressure (dDiaPr) of group 3 was significantly larger than those of groups 1 and 2. From the correlation analysis, it can be seen that age, Hoehn and Yahr (H&Y) stage, dSysPr, and dDiaPr had a weak positive correlation with the WR. The total CASS score was significantly higher in group 3 compared with groups 1 and 2. The WR had a moderate positive correlation with the cardiosympathetic score and the total CASS score. CONCLUSION: The WR is related to autonomic dysfunction. An I-123 MIBG cardiac scan is considered to be a good method to evaluate not only the differential diagnosis of Parkinson's disease but also the degree of autonomic dysfunction.

Comparison between ticagrelor and clopidogrel on myocardial blood flow in patients with acute coronary syndrome, using 13 N-ammonia positron emission tomography.

BACKGROUND: The PLEIO (comParison of ticagreLor and clopidogrEl on mIcrocirculation in patients with acute cOronary syndrome) study showed that 6 months of ticagrelor therapy significantly improved microvascular dysfunction in acute coronary syndrome (ACS) patients with stent implantation compared to clopidogrel. Improved microvascular function may affect myocardial blood flow (MBF). We compared the effects of ticagrelor and clopidogrel on MBF over a 6-month follow-up period among patients diagnosed with ACS treated with percutaneous coronary intervention (PCI). METHODS: In the PLEIO trial, 120 participants were randomized to receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily after at least 6 months. 13 N-ammonia positron emission tomography (PET) imaging was performed in 94 patients to measure MBF at the 6-month follow-up visit. RESULTS: On a per-patient level, MBF (1.88 ±â€¯0.52 versus 1.67 ±â€¯0.64 mL/min per gram, P = .01) was significantly higher with ticagrelor compared with clopidogrel in the hyperemic state, but not under resting state (0.75 ±â€¯0.24 versus 0.75 ±â€¯0.19 mL/min per gram, P = .84). On a culprit-vessel analysis, the resting MBF was similar (0.69 ±â€¯0.20 versus 0.70 ±â€¯0.21, P = .89) between the two groups. However, the hyperemic MBF and myocardial flow reserve in the ticagrelor group were significantly higher compared with clopidogrel (1.75 ±â€¯0.46 versus 1.52 ±â€¯0.59, P = .03 and 2.71 ±â€¯0.89 versus 2.20 ±â€¯0.81, P = .02, respectively). These differences were not observed in non-culprit vessels. CONCLUSIONS: Maintenance treatment of ticagrelor increased the hyperemic MBF and myocardial flow reserve compared with clopidogrel. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02618733.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

Comparative effectiveness of different antiplatelet agents at reducing TNF-driven inflammatory responses in a mouse model.

Antiplatelet drugs are conventionally used as treatments because of their anti-coagulation functions. However, their pleiotropic effects are of great significance to the treatment of ischaemic cardiovascular diseases. Many studies have reported that an excessive amount of inflammation driven by tumour necrosis factor (TNF) is closely related to the prevalence of atherosclerosis. As the drug selection criteria and evaluation methods related to the anti-TNF activity of antiplatelet drugs remain limited, our investigation of these drugs should prove beneficial. In this study, we compared the anti-TNF activity of three antiplatelet agents, namely clopidogrel, sarpogrelate, and cilostazol, using the TNF-induced inflammatory mouse model. After the oral administration of these drugs, acute inflammation was induced via injection of lipopolysaccharide (LPS) or D-galactosamine (D-gal) and TNF. Serum TNF levels, and the mRNA and protein expression levels of TNF in mouse heart tissue, macrophage accumulation in aortic lesions, and mouse survival were analysed to compare the anti-TNF effects of the three antiplatelet agents. Of the three antiplatelet agents, cilostazol significantly reduced the different levels under the most effective observation. In addition, cilostazol was found to attenuate the TNF-stimulated phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) p65 in the aortic vascular smooth muscle cell line, MOVAS-1 and the D-gal plus TNF-challenged heart tissue of mouse. Therefore, cilostazol is the most ideal of the three antiplatelet drugs for the treatment of TNF-mediated inflammatory disorders.

Cerebral Amyloid Quantification in Cognitively Normal Korean Adults Using F-18 Florbetaben PET.

PURPOSE: To investigate regional cerebral amyloid beta retention in cognitively normal Korean adults using F-18 florbetaben (FBB). METHODS: We prospectively analyzed F-18 FBB positron emission tomography (PET)/CT scans of 30 cognitively healthy adults (age range, 50-70 years) using automated quantification. The standardized uptake value ratios (SUVRs) of F-18 FBB were calculated for predefined regions by normalizing the regional count with cerebellar cortex. RESULTS: The distribution of amyloid beta for each brain region revealed no age-related trends (p > 0.05). From all subjects, mean SUVR of amyloid deposit was 1.30 ± 0.18. The right parietal lobe showed the highest SUVR value (1.46 ± 0.23), whereas the right frontal lobe and left precuneus showed the lowest SUVR (1.23 ± 0.25). CONCLUSIONS: We provide reference values of normative data obtained from healthy elderly Koreans and suggest its use for accurate diagnosis of patients with Alzheimer's disease.

Correlation of Early-Phase F-18 Florapronal PET with F-18 FDG PET in Alzheimer's Disease and Normal Brain.

PURPOSE: F-18 florapronol (FPN) is the commercially recognized beta-amyloid positron emission tomography (PET) radiotracer in Korea. This study compared the early F-18 florapronol PET with F-18 fluorodeoxyglucose (FDG) PET between healthy controls (HC) and Alzheimer's dementia (AD) patients. METHODS: A total of 29 subjects (15 HC and 14 AD subjects) underwent F-18 FPN PET and F-18 FDG PET. F-18 FDG PET image was acquired from 30 to 60 min and F-18 FPN PET for 0 to 10 min. F-18 FPN and F-18 FDG images were spatially normalized with transformation matrices obtained from individual CT images and standardized uptake value ration (SUVR) from cerebellum area, and the global mean was calculated using PMOD 3.6. Pearson's correlation coefficients between F-18 FDG and early F-18 FPN for predefined cortical brain regions were calculated. RESULTS: We compared the F-18 FDG and F-18 FPN for SUVR of a specific region in global mean normalization and cerebellum normalization, and most of the correlation coefficient was higher in global mean normalization. In global mean normalization, the correlation coefficient for SUVR of HC was higher than that of AD in all brain regions. CONCLUSIONS: Early F-18 FPN study can be used as a proxy marker for the F-18 FDG PET.

The Effect of Clinical Characteristics and Subtypes on Amyloid Positivity in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Amyloid deposits in positron-emission tomography (PET) imaging of MCI patients imply a higher risk for advancing to dementia, with rates of 10%-15% yearly. The purpose of this study was to investigate the clinical characteristics of subgroups of amnestic MCI (aMCI) that may have a higher impact on amyloid positivity. METHODS: We recruited 136 aMCI patients. All patients underwent a 20-minute F-18 florbetaben or flutemetamol PET scan. We classified amyloid PET images as positive or negative according to a semi-quantitative method. We evaluated the amyloid positivity of subgroups of aMCI (early vs. late type, single vs. multiple amnestic type, verbal vs. verbal, and visual amnestic type), and compared baseline clinical characteristics including key risk factors, apolipoprotein E4 (apoE4) genotype, and neuropsychological assessments with amyloid positivity in aMCI. RESULTS: The amyloid positivity in total aMCI was 41%. The positivity rate according to subgroup of aMCI were as follow: Late aMCI (49%) vs. early aMCI (33%) (p=0.13), multiple aMCI (40%) vs. single aMCI (38%) (p=0.51), and verbal and visual aMCI (59%) vs. verbal aMCI (35%) (p=0.01), respectively. The mean age and the frequency of apoE4 allele of the amyloid-positive group was higher than that of the amyloid-negative group in aMCI (p<0.01). CONCLUSIONS: We found that the amyloid positivity was related to patterns of clinical subtypes, characteristics, and risk factors in patients with aMCI.