Dopamine receptor and dopamine transporter in obesity: A meta-analysis.

The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging." Body mass index (BMI) and the corresponding binding potential (BPND ) were extracted from figures in each study using Engauge Digitizer, version 12.1, and plotted for radiopharmaceuticals and regions of interest (ROIs). Five studies involving 119 subjects with DR and five studies including 421 subjects with DAT were eligible for inclusion in this study. In overweight or obese subjects with BMI of 25 kg/m2 or higher, DR availability from 11 C-Racloprie was negatively associated with BMI. However, DR availability from 11 C-PHNO was positively associated with BMI. DAT ratio was calculated after dividing DAT availabilities of overweight/obese BMI with mean DAT availabilities of normal BMI. The association between DAT ratio and BMI was not significant regardless of radiopharmaceuticals. In conclusion, dopamine plays a main role in the reward system with regard to obesity. Overweight and obese subjects had negative association between DR availability from 11 C-Raclopride and BMI. However, the association of DR availability with BMI was dependent on radiopharmaceuticals. DAT availability did not show the significant relationship with BMI regardless of radiopharmaceuticals.

The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction.

Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60-4.2] versus 0.20 [0.10-0.40], p = 0.021 by Mann-Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.

Association of androgen receptor expression with glucose metabolic features in triple-negative breast cancer.

BACKGROUND: Androgen receptor (AR) is a potential therapeutic target in triple-negative breast cancer (TNBC). We aimed to elucidate the association of AR expression with glucose metabolic features in TNBC. METHODS: Two independent datasets were analyzed: FDG PET data of our institution and a public dataset of GSE135565. In PET analysis, patients with TNBC who underwent pretreatment PET between Jan 2013 and Dec 2017 were retrospectively enrolled. Clinicopathologic features and maximum standardized uptake value (SUVmax) of tumors were compared with AR expression. In GSE135565 dataset, glycolysis score was calculated by the pattern of glycolysis-related genes, and of which association with SUVmax and AR gene expression were analyzed. RESULTS: A total of 608 female patients were included in the PET data of our institution. SUVmax was lower in AR-positive tumors (P < 0.001) and correlated with lower AR expression (rho = -0.26, P < 0.001). In multivariate analysis, AR was a deterministic factor for low SUVmax (P = 0.012), along with other key clinicopathologic features. In the GSE135565 dataset, AR expression also exhibited a negative correlation with SUVmax (r = -0.34, P = 0.001) and the glycolysis score (r = -0.27, P = 0.013). CONCLUSIONS: Low glucose metabolism is a signature of AR expression in TNBC. It is suggested that evaluation of AR expression status needs to be considered in clinical practice particularly in TNBC with low glucose metabolism.

Prediction of post-stroke cognitive impairment using brain FDG PET: deep learning-based approach.

PURPOSE: Post-stroke cognitive impairment can affect up to one third of stroke survivors. Since cognitive function greatly contributes to patients' quality of life, an objective quantitative biomarker for early prediction of dementia after stroke is required. We developed a deep-learning (DL)-based signature using positron emission tomography (PET) to objectively evaluate cognitive decline in patients with stroke. METHODS: We built a DL model that differentiated Alzheimer's disease (AD) from normal controls (NC) using brain fluorodeoxyglucose (FDG) PET from the Alzheimer's Disease Neuroimaging Initiative database. The model was directly transferred to a prospectively enrolled cohort of patients with stroke to differentiate patients with dementia from those without dementia. The accuracy of the model was evaluated by the area under the curve values of receiver operating characteristic curves (AUC-ROC). We visualized the distribution of DL-based features and brain regions that the model weighted for classification. Correlations between cognitive signature from the DL model and clinical variables were evaluated, and survival analysis for post-stroke dementia was performed in patients with stroke. RESULTS: The classification of AD vs. NC subjects was performed with AUC-ROC of 0.94 (95% confidence interval [CI], 0.89-0.98). The transferred model discriminated stroke patients with dementia (AUC-ROC = 0.75). The score of cognitive decline signature using FDG PET was positively correlated with age, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and negatively correlated with body mass index in patients with stroke. We found that the cognitive decline score was an independent risk factor for dementia following stroke (hazard ratio, 10.90; 95% CI, 3.59-33.09; P < 0.0001) after adjustment for other key variables. CONCLUSION: The DL-based cognitive signature using FDG PET was successfully transferred to an independent stroke cohort. It is suggested that DL-based cognitive evaluation using FDG PET could be utilized as an objective biomarker for cognitive dysfunction in patients with cerebrovascular diseases.

The association of DAT gene methylation with striatal DAT availability in healthy subjects.

BACKGROUND: DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences in reward processing. We aimed to investigate the action of DAT methylation on DAT protein expression measured by positron emission tomography (PET). METHODS: The emission data were acquired over 90 min with 50 frames after injection of 18F-FP-CIT using PET. Binding potentials (BPNDs) of ventral striatum, caudate nucleus, putamen were measured with the simplified reference tissue method. Genomic DNA was extracted from subjects' blood sampling. Methylation of 4 regions in SLC6A3 gene was assessed using bisulfite pyrosequencing. The mean percentage of methylation (%) for each cluster was calculated by taking the average of all CpG site methylation levels measured within the cluster. Subjects were assessed with the Generalized Reward and Punishment Expectancy Scales (GRAPES) that consists of 30 items related with the reward and punishment that individuals expect for their behaviors. RESULTS: Thirty-five healthy males, with an age range between 20 and 30 years, and a mean age of 24.4 ± 2.7 years, were included in this study. The mean percentage of methylation (%) from cluster C showed a trend of positive correlation with DAT availability of ventral striatum (rho = 0.3712, p = 0.0281), not significant after correction for multiple comparisons, and a significant correlation with GRAPES A: reward expectancy scale (rho = 0.7178, p < 0.0001). CONCLUSION: DAT methylation from peripheral blood showed a trend of positive correlation with DAT availability of ventral striatum in healthy subjects; however, it was not significant after correction for multiple comparison. The degrees of methylation from cluster C of DAT in peripheral blood were significantly correlated with reward scales of GRAPES A: reward expectancy scale. The association between DAT methylation and DAT expression needs to be investigated further.

Decreased 18F-Fluorodeoxyglucose Uptake in Lumbar Vertebrae of Stroke Patients.

BACKGROUND AND PURPOSE: We investigated 18F-fluorodeoxyglucose (FDG) uptake levels in the lumbar vertebrae, liver, and spleen of stroke patients with carotid atherosclerosis. METHODS: This study analyzed acute ischemic stroke patients with carotid atherosclerosis who underwent whole-body FDG positron-emission tomography between October 2015 and January 2017. FDG uptake in the lumbar vertebrae, liver, and spleen was measured and compared between stroke patients and control subjects without stroke history. Multivariate linear regression analysis was performed to identify independent factors related to FDG uptake in the proximal internal carotid artery (ICA). RESULTS: Twenty stroke patients aged 75.1±9.0 years (mean±standard deviation; 10 females) and 20 control subjects aged 62.9±10.7 years (6 females) were included. In comparison with the control group, the stroke group showed significantly higher FDG uptake in the proximal ICA (1.16±0.26 vs. 0.87±0.19, p<0.01), but significantly lower FDG uptake in the lumbar vertebrae (1.09±0.26 vs. 1.38±0.38, p=0.007) and liver (1.71±0.30 vs. 2.01±0.34, p=0.005). Multivariate linear regression analysis showed that the lumbar FDG uptake was negatively correlated with FDG uptake in the proximal ICA (standardized coefficient=-0.367, p=0.013) after adjusting for age and hypertension. CONCLUSIONS: Stroke patients showed decreased FDG uptake in the lumbar vertebrae. Further studies are warranted to evaluate the pathophysiological link between cerebral atherosclerosis and bone.

An Update on [18F]Fluoride PET Imaging for Atherosclerotic Disease.

Atherosclerosis is the leading cause of life-threatening morbidity and mortality, as the rupture of atherosclerotic plaques leads to critical atherothrombotic events such as myocardial infarction and ischemic stroke, which are the 2 most common causes of death worldwide. Vascular calcification is a complicated pathological process involved in atherosclerosis, and microcalcifications are presumed to increase the likelihood of plaque rupture. Despite many efforts to develop novel non-invasive diagnostic modalities, diagnostic techniques are still limited, especially before symptomatic presentation. From this point of view, vulnerable plaques are a direct target of atherosclerosis imaging. Anatomic imaging modalities have the limitation of only visualizing macroscopic structural changes, which occurs in later stages of disease, while molecular imaging modalities are able to detect microscopic processes and microcalcifications, which occur early in the disease process. Na[18F]-fluoride positron emission tomography/computed tomography could allow the early detection of plaque instability, which is deemed to be a primary goal in the prevention of cardiac or brain ischemic events, by quantifying the microcalcifications within vulnerable plaques and evaluating the atherosclerotic disease burden.

Development and Validation of a Risk Scoring System Derived from Meta-Analyses of Papillary Thyroid Cancer.

BACKGROUND: The aim of this study was to develop a scoring system to stratify the risk of papillary thyroid cancer (PTC) and to select the proper management. METHODS: We performed a systematic search of MEDLINE and Embase. Data regarding patients' prognoses were obtained from the included studies. Odds ratios (ORs) with statistical significance were extracted from the publications. To generate a risk scoring system (RSS), ORs were summed (RSS1), and summed after natural-logarithmic transformation (RSS2). RSS1 and RSS2 were compared to the eighth edition of the American Joint Committee on Cancer (AJCC) staging system and the 2015 American Thyroid Association (ATA) guidelines for thyroid nodules and differentiated thyroid carcinoma. RESULTS: Five meta-analyses were eligible for inclusion in the study. Eight variables (sex, tumour size, extrathyroidal extension, BRAF mutation, TERT mutation, histologic subtype, lymph node metastasis, and distant metastasis) were included. RSS1 was the best of the analysed models. CONCLUSION: We developed and validated a new RSS derived from previous meta-analyses for patients with PTC. This RSS seems to be superior to previously published systems.

Prognostic value of metabolic tumor volume and total lesion glycolysis in breast cancer: a meta-analysis.

OBJECTIVES: PET using F-fluorodeoxyglucose (FDG) has proven to be valuable in staging and monitoring of treatment response in breast cancer. We aimed to assess the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with breast cancer. METHODS: A systematic search of MEDLINE and EMBASE was performed using the keywords of breast cancer, PET, and volume. Inclusion criteria were F-FDG PET used as an initial imaging tool; studies limited to patients with breast cancer who had not undergone any treatment before PET scans; and studies reporting survival data. Event-free survival (EFS) and overall survival (OS) were considered markers of outcome. RESULTS: Nine studies comprising 975 patients were included in this study. The pooled hazard ratio (HR) for adverse events was 33.73 (P < 0.00001; I = 0%) with MTV from primary tumor and 2.89 (P < 0.00001; I = 45%) with TLG from primary tumor, meaning that primary tumors with high volumetric parameters were associated with progression or recurrence. However, the combined HRs for EFS of MTV, and TLG, and those for OS of MTV from whole-body tumor were NS. The pooled HR for OS of TLG from whole-body tumor was 2.95 (P = 0.18; I = 71%). CONCLUSION: Volumetric parameters from F-FDG PET are significant prognostic factors for outcome in patients with breast cancer. Patients with a high MTV or TLG from primary tumor have a higher risk of adverse events. Patients with a high TLG from whole-body tumor have a higher risk of deaths.

Memory performance associates with serotonin transporter in midbrain and pons in healthy subjects.

OBJECTIVE: We aimed to evaluate the association between the availability of serotonin transporter (SERT) measured by ioflupane-DaTSCAN (123I-FP-CIT) and imaged by single photon emission tomography (SPET) and memory function in healthy subjects. SUBJECTS AND METHODS: Specific binding of 123I-FP-CIT indicating SERT was achieved using a region of interest analysis. Spherical volumes of interest for midbrain and pons were defined. The cerebellum was chosen as a reference region. Specific binding ratios (SBR) in midbrain and pons representing SERT availability were measured as follows: SBR=(target-cerebellum)/cerebellum. A hundred and eighty-one healthy subjects (117 male, 64 female) were included in this study. RESULTS: Specific binding ratios of both midbrain (P=0.025) and pons (P=0.006) of males was higher than that of females. None of the SBR showed a correlation with age both in males: (midbrain; P=0.736, pons; P=0.875) and in females (midbrain; P=0.294, pons; P=0.170). In all our cases, SERT availability of midbrain correlated positively with total recall score (rho=0.159, P=0.033), and delayed recall score (rho=0.149, P=0.046). In females, the correlation between SERT availability in midbrain and delayed recall score was significant (rho=0.320, P=0.010), however, not in males (rho=0.112, P=0.229). CONCLUSION: In conclusion, we demonstrated that SERT availability was associated with memory function in healthy females from the PPMI database. Further studies are needed to clarify underlying mechanisms of this phenomenon.

Incidence, Risk Factors, and Clinical Outcomes of Acute Kidney Injury Caused by Palliative Chemotherapy in Lung Cancer.

Purpose: Acute kidney injury (AKI) affects cancer therapy outcome and increases morbidity and mortality in cancer patients. We investigated the incidence, risk factors, and clinical outcomes of AKI caused by palliative chemotherapy in lung cancer patients. Materials and Methods: Between January 2005 and November 2014, 207 lung cancer patients who had been treated with first-line palliative chemotherapy were enrolled. Renal function was assessed during every cycle of chemotherapy. AKI was defined based on changes in serum creatinine levels as described in the Kidney Disease: Improving Global Outcomes guidelines. Clinical outcomes were evaluated depending on AKI occurrence during the first-line chemotherapy. Results: Of the 207 patients, 36 (17.4%) experienced AKI. Among the 36 patients who developed AKI during chemotherapy, 33 (91.8%) had AKI stage I. Although 19 patients (52.7%) with AKI during chemotherapy progressed to chronic kidney disease (CKD), no patients were reported to progress to end-stage renal disease (ESRD). The number of chemotherapy cycles was independently associated with chemotherapy-induced AKI in multivariate analysis (OR = 1.71, 95% CI 1.29-2.26, p < 0.001). The median follow-up duration was 83 months. Patients with AKI during chemotherapy (AKI group) showed significantly longer time to treatment failure than patients without AKI (non-AKI group) (4.2 vs. 2.5 months, p < 0.001). However, the median overall survival (11.7 vs. 8.8 months, p = 0.147) and progression-free survival (5.5 vs. 5.2 months, p = 0.347) were not different between the groups. Conclusions: AKI that developed during chemotherapy was mostly of mild degree and its prognosis was favorable. The occurrence of AKI was associated with the number of chemotherapy cycles administered. AKI did not adversely affect survival of lung cancer patients during chemotherapy.

Prediction of future weight change with dopamine transporter in patients with Parkinson's disease.

Fluctuating body weight is a commonly reported nonmotor feature in patients with Parkinson's disease (PD). We hypothesised that striatal dopamine transporter (DAT) density at the time of diagnosis might play an important role in weight regulation in patients with PD. DAT density was measured from 123I-FP-CIT single-photon emission computed tomography. Region-of-interest analyses were performed to measure the specific binding of 123I-FP-CIT to DAT, and the putamen-to-caudate nucleus ratio (PCR) was calculated. Body weight was measured at baseline (W0) and at 48 months (W48). We classified subjects into three groups: weight loss, stable, and weight gain. In final analyses, 163 patients (106 men, 57 women) were included. PCR significantly differed by group in men, but not in women or across all patients. In men, PCR was slightly negatively associated with the percentage change in weight. No such correlation was found across all patients or in women. In univariate and multivariate logistic regression analyses, low PCR was associated with future weight gain in men with PD but not in women. In conclusion, striatal DAT availability at the time of diagnosis could predict subsequent weight change in men with PD.

Analysis of 18F-Fluorodeoxyglucose and 18F-Fluoride Positron Emission Tomography in Korean Stroke Patients with Carotid Atherosclerosis.

OBJECTIVE: The objective of this study was to analyze uptake patterns and intensity of 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) radioligands in carotid atheroma among stroke patients according to carotid atheroma characteristics. METHODS: Between September 2015 and January 2017, consecutive acute stroke or transient ischemic attack patients with 50% or more proximal internal carotid artery stenosis on brain computed tomography angiography were prospectively enrolled. All patients received FDG and NaF positron emission tomography (PET) evaluation when their neurological status was stabilized. Uptake values of FDG and NaF were compared by target to blood ratio (TBR) according to the calcification burden, atheroma volume and the presence of a necrotic core of carotid atheroma. RESULTS: A total of 18 patients with 36 carotid arteries were finally enrolled, with 10 patients diagnosed as acute cerebral infarction due to symptomatic carotid stenosis. FDG uptake at symptomatic carotid arteries was significantly more increased than that at asymptomatic arteries (TBR: 1.17±0.23 vs. 1.01±0.15, Mann-Whitney U-test, p=0.02), but NaF uptake was not different (TBR: 1.38±0.49 vs. 1.51±0.40, p=0.40). In terms of calcification degree, NaF uptake increased as calcification burden increased (none, 1.28±0.36; spotty, 1.29±0.29; linear, 1.74±0.44; analysis of variance, p=0.02). CONCLUSION: Carotid evaluation by FDG is superior to NaF PET in the detection of symptomatic carotid atherosclerosis among stroke patients. NaF PET uptake reflects the overall calcification burden.

BRAF-positive multifocal and unifocal papillary thyroid cancer show different messenger RNA expressions.

OBJECTIVE: Thyroid cancer is the most common malignant endocrine tumour, and its incidence has continuously increased worldwide over the past three decades. We focused on the association of multifocal papillary thyroid carcinoma (PTC) with messenger RNA (mRNA) expression to characterize how molecular and histopathologic features relate to multifocality. DESIGN: A retrospective cohort study. PATIENTS: The primary and processed data were downloaded from The Cancer Genome Atlas. A total of 490 patients were included in this study. METHODS: The statistical significance of differences in sex, age, histology, LN metastasis and recurrence were analysed using chi-squared test. To identify differentially expressed genes between BRAF (+) multifocal and unifocal PTCs and between BRAF (-) multifocal and unifocal PTCs, we used the Significance Analysis of Microarray. Over-representation analysis is conducted using CPDB. RESULTS: A total of 237 patients had BRAF (+) PTCs, whereas 253 had BRAF (-) PTCs. There were 110 patients with multifocal PTCs and 127 with unifocal PTCs in the BRAF (+) group and 116 patients with multifocal PTCs and 137 with unifocal PTCs in the BRAF (-) group. In BRAF (+) group, multifocal PTCs had increased expression of 158 mRNAs as compared to that in unifocal PTCs. Ten mRNAs were involved in Wnt-related pathways, and seven mRNAs were included in pluripotency-related pathways. CONCLUSION: Multifocal PTCs have higher expression of mRNAs in Wnt- and pluripotency-related pathways when BRAF mutation is present. This might be the mechanism that accounts for the difference between multifocal and unifocal PTCs.

Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects.

PURPOSE: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects. MATERIALS AND METHODS: The study population comprised healthy controls who underwent ¹²³I-FP-CIT single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long 3'UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1-4 (SNCA-007). RESULTS: In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=-0.277), and SNCA-E4E6 (p=0.042, rho=-0.270), but not those of CC/TT genotypes. CONCLUSION: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.