A Prospective Comparative Study of 18 F-FDOPA PET/CT Versus 123 I-MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma.

PURPOSE: This study aimed to compare the diagnostic performances of 18 F-FDOPA PET/CT and 123 I-MIBG scintigraphy with SPECT/CT for detection of pheochromocytoma and paraganglioma (PPGL). PATIENTS AND METHODS: We conducted a prospective, single-institution comparative study. Patients suspected of having PPGL or those showing recurrence and/or distant metastasis of PPGL were enrolled. The primary objective was to affirm the noninferiority of 18 F-FDOPA PET/CT for diagnostic sensitivity. Both 123 I-MIBG scintigraphy with SPECT/CT (at 4 and 24 hours) and 18 F-FDOPA PET/CT (at 5 and 60 minutes after radiotracer administration) were performed. The final diagnosis was established either pathologically or via clinical follow-up. Nuclear physicians, unaware of the clinical data, undertook image analysis. RESULTS: Thirty-two patients were evaluated: 14 of 21 with an initial diagnosis and 9 of 11 with recurrence/metastasis had PPGLs in their final diagnoses. In patient-based analyses, 18 F-FDOPA PET/CT (95.7%) exhibited noninferior sensitivity compared with 123 I-MIBG SPECT/CT (91.3%), within the predetermined noninferiority margin of -12% by a 95% confidence interval lower limit of -10%. Both modalities showed no significant difference in specificity (88.9% vs 88.9%). In the region-based analysis for the recurrence/metastasis group, 18 F-FDOPA PET/CT demonstrated significantly higher sensitivity compared with 123 I-MIBG SPECT/CT (86.2% vs 65.5%, P = 0.031) and superior interobserver agreement (κ = 0.94 vs 0.85). The inclusion of an early phase in dual-phase 18 F-FDOPA PET/CT slightly improved diagnostic performance, albeit not to a statistically significant degree. CONCLUSIONS: 18 F-FDOPA PET/CT demonstrated noninferior sensitivity and comparable specificity to 123 I-MIBG SPECT/CT in the diagnosing PPGL. Notably, in the assessment of PPGL recurrence and metastasis, 18 F-FDOPA PET/CT outperformed 123 I-MIBG SPECT/CT in terms of both sensitivity and interobserver agreement.

Serum zinc deficiency is a potential risk factor for the occurrence of levodopa-induced dyskinesia in drug-naïve Parkinson's disease.

Background: Since environmental factors, especially heavy metals, were highlighted in the pathogenesis of Parkinson's disease (PD), there are many epidemiologic studies regarding heavy metals and PD risk. However, longitudinal studies regarding the impacts of heavy metals on motor and nonmotor symptoms of PD are scarce. Methods: In the current study, we compared the serum levels of five heavy metals, such as zinc(Zn), copper(Cu), lead(Pb), mercury(Hg), and manganese(Mn), in 111 previously drug-naïve PD patients (n = 111) retrospectively. Among these 111 patients, 65 were PD patients without levodopa-induced dyskinesia (LID), while the other 46 had LID. We assembled clinical characteristics of PD and performed correlation analysis with heavy metal levels. At baseline, all subjects were examined with 18F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography/computed tomography (FP-CIT PET/CT). We used Cox proportional hazards regression analysis for determining factors relevant to the time to LID development in PD subjects. Results: Zn deficiency was significantly higher in the PD with LID group than in the PD without LID group (79.58 ± 12.28 versus 88.16 ± 15.15 µg/L). Lower serum Zn levels were significantly correlated with age of onset, levodopa equivalent daily dose (LEDD) at 3 months, and Korean version of the Mini-Mental State Examination (K-MMSE) scores (r = 0.16, p < 0.05, r = - 0.20, p < 0.01, r = 0.28, p < 0.01). Additionally, Zn deficiency was associated with a reduced time to LID development in the adjusted model (HR 0.978, 95% CI 0.956-0.999). Conclusion: This study suggests that serum Zn deficiency might be a risk factor for LID in drug-naïve PD patients.

Comparison of accuracy of breeding value for cow from three methods in Hanwoo (Korean cattle) population.

In Korea, Korea Proven Bulls (KPN) program has been well-developed. Breeding and evaluation of cows are also an essential factor to increase earnings and genetic gain. This study aimed to evaluate the accuracy of cow breeding value by using three methods (pedigree index [PI], pedigree-based best linear unbiased prediction [PBLUP], and genomic-BLUP [GBLUP]). The reference population (n = 16,971) was used to estimate breeding values for 481 females as a test population. The accuracy of GBLUP was 0.63, 0.66, 0.62 and 0.63 for carcass weight (CWT), eye muscle area (EMA), back-fat thickness (BFT), and marbling score (MS), respectively. As for the PBLUP method, accuracy of prediction was 0.43 for CWT, 0.45 for EMA, 0.43 for MS, and 0.44 for BFT. Accuracy of PI method was the lowest (0.28 to 0.29 for carcass traits). The increase by approximate 20% in accuracy of GBLUP method than other methods could be because genomic information may explain Mendelian sampling error that pedigree information cannot detect. Bias can cause reducing accuracy of estimated breeding value (EBV) for selected animals. Regression coefficient between true breeding value (TBV) and GBLUP EBV, PBLUP EBV, and PI EBV were 0.78, 0.625, and 0.35, respectively for CWT. This showed that genomic EBV (GEBV) is less biased than PBLUP and PI EBV in this study. In addition, number of effective chromosome segments (Me) statistic that indicates the independent loci is one of the important factors affecting the accuracy of BLUP. The correlation between Me and the accuracy of GBLUP is related to the genetic relationship between reference and test population. The correlations between Me and accuracy were -0.74 in CWT, -0.75 in EMA, -0.73 in MS, and -0.75 in BF, which were strongly negative. These results proved that the estimation of genetic ability using genomic data is the most effective, and the smaller the Me, the higher the accuracy of EBV.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Association between tumor 18F-fluorodeoxyglucose metabolism and survival in women with estrogen receptor-positive, HER2-negative breast cancer.

We examined whether 18F-fluorodeoxyglucose metabolism is associated with distant relapse-free survival (DRFS) and overall survival (OS) in women with estrogen receptor (ER)-positive, HER2-negative breast cancer. This was a cohort study examining the risk factors for survival that had occurred at the start of the study. A cohort from Asan Medical Center, Korea, recruited between November 2007 and December 2014, was included. Patients received anthracycline-based neoadjuvant chemotherapy. The maximum standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was measured. The analysis included 466 women. The median (interquartile range) follow-up period without distant metastasis or death was 6.2 (5.3-7.6) years. Multivariable analysis of hazard ratio (95% confidence interval [CI]) showed that the middle and high tertiles of SUV were prognostic for DRFS (2.93, 95% CI 1.62-5.30; P < 0.001) and OS (4.87, 95% CI 1.94-12.26; P < 0.001). The 8-year DRFS rates were 90.7% (95% CI 85.5-96.1%) for those in the low tertile of maximum SUV vs. 73.7% (95% CI 68.0-79.8%) for those in the middle and high tertiles of maximum SUV. 18F-fluorodeoxyglucose PET/CT may assess the risk of distant metastasis and death in ER-positive, HER2-negative patients.

Prediction of renal function improvement in azotemic patients using glomerular filtration rate from 99mTc-DTPA renal scan: An observational study.

ABSTRACT: This study aimed to evaluate the ratio of glomerular filtration rate (GFR) from 99mTc-diethylenetriamine-pentaacetic acid dynamic renal scan (GFRSCAN) to estimated GFR (eGFR) as a predictor of renal function improvement in patients with azotemia.A retrospective review of medical records was conducted to identify consecutive patients with newly discovered or aggravated azotemia who underwent 99mTc-diethylenetriamine-pentaacetic acid renal scan. Significant renal function improvement was defined as ≥100% and ≥10 mL/min improvement of eGFR at 12 weeks compared to eGFR on the day of renal scan (eGFR0). The GFRSCAN/eGFR0 ratio was evaluated as a predictor of significant renal function improvement using logistic regression and receiver operating characteristic (ROC) curve analyses. Added value of the GFRSCAN/eGFR0 ratio in the prediction of significant renal function improvement were demonstrated by adjusting for best clinical predictor variables.The eligibility criteria were met by 224 patients, among whom 22 patients (9.8%) showed significant renal function improvement. The odds ratios of the GFRSCAN/eGFR0 ratio for predicting significant renal function improvement were 1.76 (95% confidence interval [CI]: 1.26-2.45, P < .001) in the univariable analysis and 1.70 (95% CI: 1.19-2.42, P = .003) after adjusting for clinical variables. The area under the ROC curve of the GFRSCAN/eGFR0 ratio for predicting significant renal function improvement was 0.762 (95% CI: 0.648-0.871). The addition of the GFRSCAN/eGFR0 ratio to the best clinical prediction model raised the area under the ROC curve from 0.726 to 0.794, and this increment was statistically significant (P = .02).The GFRSCAN/eGFR ratio can predict renal function improvement in patients with azotemia. Future prospective studies are necessary to validate its potential clinical utilities.

A practical individualized radiation precaution based on the dose rate at release time after inpatient 131I ablation therapy.

INTRODUCTION: Retained radioactivity of 131I after ablation therapy largely differs in each patient according to factors including the amount of remnant thyroid tissue, renal function, and use of recombinant human thyroid-stimulating hormone. To reduce unnecessary restriction of patient's daily life after inpatient 131I ablation therapy, we propose a practical individualized method for radiation precaution based on dose rate at release time. METHODS: We evaluated 215 patients with differentiated thyroid cancer who underwent inpatient 131I ablation therapy following total thyroidectomy. Effective dose equivalent rates at 1-m distance were measured upon release (EDRR) on day 2 and during delayed whole-body scan (EDRD) visits on day 6‒8 after 131I administration. The biexponential model was designed to estimate total effective dose equivalent to others. To assess conservativeness of our model, EDRD estimated by our model was compared with measured EDRD. EDRR-based periods of precaution not to receiving 1 mSv of radiation exposure were estimated and compared with those based on administered radioactivities on American Thyroid Association (ATA) recommendations. RESULTS: The EDRR ranged from 1.0-48.9 µSv/hr. The measured EDRD were equal to or lower than estimated EDRD in all patients, except for one, indicating that our model is sufficiently conservative. According to our model, no subjects needed additional daytime restriction after release. The maximum permissible times for public transportation use were longer in all patients compared with those based on administered radioactivities. Nighttime restriction periods were significantly shorter than those based on administered radioactivity; median periods requiring sleeping apart were 0 (range, 0‒5), 4 (range, 1‒14), and 3 (range, 2‒13) days after release in patients treated with radioactivity doses of 2.96, 5.50, and 7.40 GBq, respectively, needing 8, 16, and 19 additional days, respectively, based on administered radioactivity. CONCLUSIONS: Radiation safety instructions using proposed method based on EDRR of individual patient could safely reduce the burden of radiation precaution.

Prognostic Value of 18F-FDG PET in Neuroendocrine Neoplasm: A Systematic Review and Meta-analysis.

OBJECTIVES: Accurate assessment of the prognosis is critical for the rational treatment of neuroendocrine neoplasms (NENs). We performed a systematic review and meta-analysis of the prognostic value of 18F-FDG PET for NENs. PATIENTS AND METHODS: PubMed and Embase databases were searched up to September 2020 for studies that evaluated 18F-FDG PET as prognostic factors in patients with NENs with overall survival (OS) and event-free survival (EFS) as outcomes. Hazards ratios (HRs) comparing high and low FDG uptakes were pooled using the DerSimonian-Laird method. Publication bias was assessed and adjusted for using the trim-and-fill method. Metaregression and subgroup analyses were performed to explore the cause of heterogeneity. RESULTS: Twenty-three studies (1799 patients) were included. The overall pooled HRs of high FDG uptake on EFS and OS were 2.84 (95% confidence interval [CI], 2.21-3.64) and 3.50 (95% CI, 2.42-4.12), respectively. Publication biases were present regarding both EFS and OS (P = 0.0342 and 0.0009, respectively). After adjustment, effect sizes remained significant for EFS and OS (adjusted HR, 2.26 [95% CI, 1.76-2.89]; 3.16 [95% CI, 2.42-4.12]). In metaregression analyses, the proportion of grade 3 tumors positively correlated with the HR of OS (adjusted P = 0.0422). CONCLUSIONS: 18F-FDG PET is a significant prognostic factor in patients with NENs. 18F-FDG PET might be a useful prognostic biomarker in conjunction with the histologic grade and can help select the optimal treatment.

Prognostic Significance of Pretreatment 18F-FDG PET/CT Volumetric Parameters in Patients With Colorectal Liver Metastasis: A Systematic Review and Meta-analysis.

PURPOSE: Colorectal liver metastasis (CRLM) remains a clinical challenge due to the lack of reliable prognostic parameters. We performed a systematic review and meta-analysis of the prognostic value of pretreatment 18F-FDG PET/CT volumetric parameters for hepatic metastatic lesions (HMLs) in patients with CRLM. METHODS: A systematic search was performed using the following combination of keywords: CRLM, FDG, PET, and prognosis. The inclusion criteria were studies using 18F-FDG PET/CT as an imaging tool before treatment, including volumetric parameters (metabolic tumor volume [MTV] and total lesion glycolysis [TLG]) for HMLs, and reported survival data. Event-free survival and overall survival were considered as survival markers. The effect on survival was determined by the effect size of the hazard ratio (HR) with 95% confidence interval (CI). RESULTS: Our systematic search identified 668 records, and a total of 10 studies comprising 494 patients were included. The pooled HRs of the prognostic value of the MTV and TLG for event-free survival were 1.55 (95% CI, 1.21-1.99; P = 0.0006) and 1.64 (95% CI, 1.23-2.19; P = 0.0009) with significance, respectively. The pooled HRs of the prognostic value of the MTV and TLG for overall survival were 1.72 (95% CI, 1.32-2.23; P < 0.0001) and 2.09 (95% CI, 1.48-2.96; P < 0.0001) with significance, respectively. CONCLUSIONS: Higher MTV and TLG for HMLs before treatment were identified as worse prognostic parameters in patients with CRLM. The MTV and TLG of 18F-FDG PET/CT could be used as predictors of prognosis.

Assessment of naive indolent lymphoma using whole-body diffusion-weighted imaging and T2-weighted MRI: results of a prospective study in 30 patients.

BACKGROUND: We prospectively evaluated the diagnostic utility of whole-body diffusion-weighted imaging with background body signal suppression and T2-weighted short-tau inversion recovery MRI (WB-DWIBS/STIR) for the pretherapeutic staging of indolent lymphoma in 30 patients. METHODS: This prospective study included 30 treatment-naive patients with indolent lymphomas who underwent WB-DWIBS/STIR and conventional imaging workup plus biopsy. The pretherapeutic staging agreement, sensitivity, and specificity of WB-DWIBS/STIR were investigated with reference to the multimodality and multidisciplinary consensus review for nodal and extranodal lesions excluding bone marrow. RESULTS: In the pretherapeutic staging, WB-DWIBS/STIR showed very good agreement (κ = 0.96; confidence interval [CI], 0.88-1.00), high sensitivity (93.4-95.1%), and high specificity (99.0-99.4%) for the whole-body regions. These results were similar to those of 18F-FDG-PET/CT, except for the sensitivity for extranodal lesions. For extranodal lesions, WB-DWIBS/STIR showed higher sensitivity compared to 18F-FDG-PET/CT for the whole-body regions (94.9-96.8% vs. 79.6-86.3%, P = 0.058). CONCLUSION: WB-DWIBS/STIR is an effective modality for the pretherapeutic staging of indolent lymphoma, and it has benefits when evaluating extranodal lesions, compared with 18F-FDG-PET/CT.

Genetic alterations associated with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in head and neck squamous cell carcinoma.

BACKGROUND: We investigated the relationship between genetic alterations and 18F-FDG PET/CT findings in head and neck squamous cell carcinoma (HNSC). METHODS: Using mRNA-sequences of HNSC samples (480 patients) from the Cancer Genome Atlas (TCGA) portal, gene coexpression networks were constructed via a weighted correlation network analysis (WGCNA) algorithm, and their association with the tumor-to-blood signal ratio on 18F-FDG PET/CT data (21 patients) was explored. An elastic-net regression model was developed to estimate the PET tumor-to-blood ratio from the gene networks and to derive an FDG signature score (FDGSS). The FDGSS was evaluated with regard to clinical variables and general mutational profiles, as well as alterations to oncogenic signaling pathways. FINDINGS: The FDGSS values differed across clinical stages (p = 0.027), HPV-status (p< 0.001), and molecular subtypes of HNSC (p< 0.001). Multivariate Cox regression demonstrated that FDGSS was an independent predictor for overall (p = 0.019) and progression-free survival (p = 0.024). FDGSS positively correlated with total mutation rate (p = 0.016), aneuploidy (p < 0.001), and somatic copy number alteration scores (p < 0.001). CDKN2A in the cell cycle pathway (q = 0.014) and the TP53 gene in the TP53 pathway (q = 0.005) showed significant differences between high and low FDGSS patients. CONCLUSION: FDGSS based on the gene coexpression network was associated with the mutational landscape of HNSC. 18F-FDG PET/CT is therefore a valuable tool for the in vivo imaging of these cancers, being able to visualize the glucose metabolism of the tumor and allow inferences to be made on the underlying genetic alterations in the tumor.

Correlation between private education costs and parental depression in South Korea.

BACKGROUND: In Korea, higher education has rapidly grown influenced by sociocultural tradition. Parents invest a significant portion of their household income in their children's education. Private education has been considered to greatly affect students' psychology and behavior. However, past research has largely neglected to study parents who pay these costs. Since household income and education level are important determinants of socioeconomic status (SES), education expenditures are likely to cause depressive symptoms. Therefore, the study aimed to investigate the correlation between private education costs and parental depression in South Korea. METHODS: Data were collected from the Korean Welfare Panel Study (KoWePS, 2015, 2018). The sample analyzed consisted of 397 and 337 fathers and 403 and 370 mothers in 2015 and 2018, respectively. The independent variable in this study was the proportion of private education cost. This proportion was calculated by dividing each household's private education costs by its equivalized household disposable income (EHDI) and multiplying this number by 100. The main dependent variable was parental responses to the Center for Epidemiologic Studies Depression Scale-11 (CESD-11). Using a generalized linear model, we investigated the effects of the proportion of private education cost on parental depression. RESULTS: The results showed that fathers with higher proportions of private education cost exhibited higher CESD-11 scores compared to fathers with lower proportions cost (moderate: ß = 0.419, S. E = 0.164, p = 0.0105; high: ß = 0.476, S. E = 0.178, p = 0.0076), indicating that a higher ratio of private education cost may negatively affect depression in fathers. However, there was no discernable correlation between mothers' CESD-11 scores and the proportion of private education cost (moderate: ß = - 0.078, S. E = 0.250, p = 0.7555; high: ß = 0.003, S. E = 0.215, p = 0.9882). CONCLUSIONS: These results may be explained by the tendency for fathers to experience greater economic burdens than mothers in patriarchal Korean society.

Compartmental-modelling-based measurement of murine glomerular filtration rate using 18F-fluoride PET/CT.

Accurate measurement of glomerular filtration rate (GFR) is essential for optimal decision making in many clinical settings of renal failure. We aimed to show that GFR can be accurately measured using compartmental tracer kinetic analysis of 18F-fluoride dynamic PET/CT. Twenty-three male Sprague-Dawley rats of three experimental groups (cyclosporine-administered [n = 8], unilaterally nephrectomized [n = 8], and control [n = 7]) underwent simultaneous 18F-fluoride dynamic PET/CT and reference 51Cr-EDTA GFR (GFRCrEDTA) test at day 0 and post-intervention day 3. 18F-fluoride PET GFR (GFRF-PET) was calculated by multiplying the influx rate and functional kidney volume in a single-tissue-compartmental kinetic model. Within-test repeatability and between-test agreement were evaluated by intraclass correlation coefficient (ICC) and Bland-Altman analysis. In the control group, repeatability of GFRF-PET was excellent (ICC = 0.9901, repeatability coefficient = 12.5%). GFRF-PET significantly decreased in the renally impaired rats in accordance with respective GFRCrEDTA changes. In the pooled population, GFRF-PET agreed well with GFRCrEDTA with minimal bias (-2.4%) and narrow 95% limits of agreement (-25.0% to 20.1%). These data suggest that the single-compartmental kinetic analysis of 18F-fluoride dynamic PET/CT is an accurate method for GFR measurement. Further studies in humans are warranted.

Diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study.

BACKGROUND: A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol (18F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer. METHODS: We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative 18F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of 18F-FES, with dosing primarily determined by radiation dosimetry analysis. 18F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569. FINDINGS: Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive 18F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded. INTERPRETATION: The high negative percent agreement between 18F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18F-FES PET-CT when retesting oestrogen receptor status is not feasible. FUNDING: Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.

Cerebrospinal Fluid Levels of Autophagy-related Proteins Represent Potentially Novel Biomarkers of Early-Stage Parkinson's Disease.

The roles of autophagy-related proteins as diagnostic or monitoring biomarkers in Parkinson's disease (PD) have not been clearly elucidated. We recruited 32 patients with early-stage PD and 28 control subjects, and evaluated parkinsonian motor symptoms and dopamine transporter imaging data. Cerebrospinal fluid (CSF) levels of LC3B, Beclin1, and LAMP-2 were estimated using ELISAs, and CSF levels of ATG5, ATG7, and p62 were examined by immunoblotting. Additionally, we also assessed the levels of α-synuclein, total tau, and phosphorylated tau in CSF using ELISAs. Significant differences in the levels of LC3B, LAMP-2, and Beclin1 were observed between the PD and control groups. Using 29.8 pg/mL as the cut-off value for a diagnostic biomarker of PD, CSF LC3B levels exhibited high sensitivity (96.9%) and specificity (89.3%) with an area under the curve of 0.982. Furthermore, LC3B was significantly correlated with the asymmetry index in the caudate and putamen, as estimated by a semi-quantitative analysis of [18F] N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET). CSF levels of LC3B represented a potential diagnostic and prognostic biomarker of early-stage PD in patients. Based on our findings, molecular biological changes in PD are associated with dysregulation of the lysosomal autophagy pathway.

Is 18F-FDG PET/CT useful for the differential diagnosis of solitary pulmonary nodules in patients with idiopathic pulmonary fibrosis?

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a single nodule detected on chest CT risks a critical adverse outcome. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is recognized to be useful for differentiating between benign and malignant solitary pulmonary nodules (SPN) in patients without IPF, but its diagnostic accuracy has not been investigated in patients with IPF. In this study, therefore, we investigated whether 18F-FDG PET/CT is useful for the differential diagnosis of SPNs in patients with IPF. METHODS: From the IPF patient cohort of our institution, we retrospectively reviewed 55 patients (54 men, 1 woman; age 67.8 ± 7.6 years) with an SPN sized 8-30 mm (mean 18.5 ± 5.7 mm) who underwent chest CT followed by 18F-FDG PET/CT between April 2004 and March 2016. The 18F-FDG uptake of the SPN was analyzed visually and semiquantitatively, and these determinations were compared with the final diagnosis obtained by pathology (n = 52) or imaging follow-up (n = 3). RESULTS: The final diagnoses showed that 41 (75%) of the SPNs were malignant (21 squamous cell carcinomas, 9 adenocarcinomas, 5 small-cell carcinomas, 4 mixed-type carcinomas, 1 large-cell neuroendocrine carcinoma, and 1 sarcoid carcinoma) and 14 (25%) were benign. The determination of malignant SPNs by visual analysis of the PET/CT images had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 98, 86, 95, and 92%, respectively. The semiquantitative analysis using a maximum standardized uptake value of 2.0 as the cut-off had a sensitivity, specificity, PPV, and NPV of 95, 93, 98, and 87%, respectively. CONCLUSIONS: 18F-FDG PET/CT is useful for differentiating benign and malignant SPNs in patients with IPF, as it is for patients without IPF.

Fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography for the detection of proximal synchronous lesions in patients with obstructive colorectal cancer.

BACKGROUND AND AIM: We aimed to investigate the ability of fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) to detect synchronous neoplasms, specifically obstructive colorectal cancer (CRC) and CRC in the proximal colon and to suggest a management strategy based on FDG PET/CT findings. METHODS: From the CRC surgery database of our institution, 518 patients with obstructive CRC whose proximal colon could not be examined by colonoscopy and who underwent preoperative FDG PET/CT were eligible for this study. Of these, final analyses were performed in 345 patients who had reference standards for the proximal colon, which were a surgical colectomy specimen and/or postsurgical colonoscopy. The per-patient and per-lesion performances of FDG PET/CT for synchronous CRC diagnosis were determined. RESULTS: Of 345 patients, 14 (4.1%) had 14 proximal synchronous CRCs. Thirty-four patients showed 39 areas of abnormal FDG uptake on PET/CT in the colon proximal to the obstructive CRC. PET/CT detected all of the 14 proximal synchronous CRCs. The per-patient PET/CT sensitivity, specificity, positive predictive value, and negative predictive value for proximal synchronous CRC were 100%, 93.9%, 41.2%, and 100%, respectively. Per-lesion values were 100%, 92.6%, 35.9%, and 100%, respectively. The per-lesion sensitivity and negative predictive value of PET/CT for advanced adenoma were 45.5% and 92.7%, respectively. CONCLUSIONS: The FDG PET/CT shows a high sensitivity and negative predictive value for the detection of proximal synchronous CRC in patients with obstructive CRC, enabling negative findings in the proximal colon on PET/CT to definitively exclude proximal synchronous CRC. Preoperative PET/CT recommended to determine the proper surgical plan in patients with obstructive CRC.

A Randomized Feasibility Study of 18F-Fluoroestradiol PET to Predict Pathologic Response to Neoadjuvant Therapy in Estrogen Receptor-Rich Postmenopausal Breast Cancer.

The aim of this study was to explore the ability of 18F-fluoroestradiol (18F-FES) PET/CT imaging to predict pathologic response to neoadjuvant therapy in postmenopausal women with estrogen receptor (ER)-rich breast cancer. Methods: This was a prospective, single-center study conducted as a substudy of the neoadjuvant study of chemotherapy versus endocrine therapy in postmenopausal patients with primary breast cancer (NEOCENT) trial. Patients with ER-rich breast cancer were randomized to neoadjuvant chemotherapy (NC) or neoadjuvant endocrine therapy (NET). The baseline SUVmax of 18F-FES PET/CT was measured. The pathologic response was assessed by the Miller-Payne system as nonresponse (grades 1 and 2) and response (grades 3-5). Results: Twenty-six patients were enrolled, with pathologic response achieved in 25 (NC, 12; NET, 13). Two patients achieved pathologic complete response after NC, but the remaining 23 patients had residual disease after NC or NET. Eight of 12 patients responded to NC, and 4 of 13 to NET; the difference was marginally significant (P = 0.07). In the NC group, the 2 patients with 18F-FES-negative tumors and none of the 10 patients with 18F-FES-avid tumors achieved pathologic complete response (P = 0.02). No difference in the SUVmax between responders and nonresponders was observed in either group. However, 5 of 7 NC patients with a baseline SUVmax of less than 7.3 achieved pathologic response, whereas none of the 5 NET patients with an SUVmax of less than 7.3 were responders (P = 0.03). The SUVmax values of the NC group were negatively correlated with percentage reduction of tumor cellularity (r = -0.63, P = 0.03), whereas those of the NET group showed positive correlation (r = 0.62, P = 0.02). During the median follow-up of 74 mo (range, 44-85 mo), recurrence occurred in only 4 NET patients. In patients with an SUVmax of less than 7.3, recurrence occurred in none of the 8 NC patients and 2 of the 5 NET patients (P = 0.13). Conclusion: Postmenopausal women who are ER-positive, but 18F-FES-negative, may benefit from NC rather than NET. 18F-FES PET/CT has the potential to predict response to neoadjuvant therapy in postmenopausal women with ER-rich breast cancer.

Similar Impact of Clopidogrel or Ticagrelor on Carotid Atherosclerotic Plaque Inflammation.

BACKGROUND: Platelets play an important role in inflammation. Inhibitors of the P2Y12 receptor, which is involved in platelet activation, may have a direct effect on carotid atherosclerotic plaque inflammation. HYPOTHESIS: We compared the effects of clopidogrel and ticagrelor therapy for carotid atherosclerotic plaque inflammation using 18 F-fluorodeoxyglucose ( 18 FDG) positron emission tomography (PET) imaging. METHODS: Fifty patients with acute coronary syndrome and ≥1 18 FDG uptake in the carotid artery (target-to-background ratio [TBR] ≥1.6) were randomized to either clopidogrel or ticagrelor groups. Of these, 46 completed PET examinations at baseline and at 6 months. The primary endpoint was the percent change in TBR of the index vessel at the most diseased segment (MDS). RESULTS: Baseline characteristics were similar between the 2 groups. At 6-month follow-up, low-density lipoprotein cholesterol and C-reactive protein significantly decreased in both groups (P < 0.001). The TBR of the index vessel and aorta significantly decreased in both groups (P < 0.01). The percent change in the MDS TBR of the index vessel was numerically but not significantly lower in the clopidogrel group than in the ticagrelor group (-9.5 ± 14.6% vs -13.5 ± 19.3%; P = 0.427). Likewise, the percent change in the whole-vessel TBR of the index vessel was not different between the 2 groups (P = 0.166). Similar findings were observed for changes in the MDS TBR (P = 0.412) or whole-vessel TBR of the aorta (P = 0.363). CONCLUSIONS: Carotid atherosclerotic plaque inflammation significantly decreases to a similar degree following 6 months of either clopidogrel or ticagrelor treatment.

Metformin discontinuation less than 72 h is suboptimal for F-18 FDG PET/CT interpretation of the bowel.

OBJECTIVE: Metformin-induced [F-18] fluorodeoxyglucose (FDG) bowel uptake can hinder positron emission tomography/computed tomography (PET/CT) evaluation of the bowel. This study aimed to investigate the segmental bowel uptake of FDG according to metformin discontinuation times up to 72 h. METHODS: We retrospectively divided 240 diabetic patients into four groups: metformin discontinuation <24 h (group A; n = 86), 24-48 h (group B; n = 40), 48-72 h (group C; n = 12), and no metformin (control group; n = 102). Segmental FDG bowel uptakes were measured visually (four-point scale) and semi-quantitatively (maximum standardized uptake value). RESULTS: Compared with the control group, FDG uptake increased significantly from the ileum to the rectosigmoid colon in group A, from the transverse to the rectosigmoid colon in group B, and from the descending colon to the rectosigmoid colon in group C in both visual and semi-quantitative analyses. CONCLUSIONS: Metformin discontinuation for <72 h is likely suboptimal for PET/CT image interpretation, especially with respect to the distal segments of the colon.