Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

BACKGROUND: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. METHODS: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. RESULTS: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT were administered in 167 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response (HR 3.11, 95% CI 1.73-5.58, P <0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels <37 IU/L (median survival; 35.5 vs. 20.9 mo, P <0.001) and CA19-9 levels ≥37 IU/L (median survival; 34.3 vs. 17.8 mo, P =0.03). In patients suspected to be Lewis antigen negative, predictive performance of MTV was found to be limited ( P =0.84). CONCLUSION: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

One-Year Longitudinal Changes in Tau Accumulation on [18F]PI-2620 PET in the Alzheimer Spectrum.

We investigated the longitudinal changes in cortical tau accumulation and their association with cognitive decline in patients in the Alzheimer disease (AD) continuum using 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([18F]PI-2620) PET. Methods: We prospectively enrolled 52 participants (age, 69.7 ± 8.4 y; 18 men and 34 women): 7 with normal cognition, 28 with mild cognitive impairment, and 17 with AD. They all completed the [18F]PI-2620 and [18F]florbetaben PET, MRI, and neuropsychologic tests at baseline and, excepting the [18F]florbetaben PET, at the 1-y follow-up. Amyloid-ß (Aß) PET images were visually scored as positive (+) or negative (-). Patients on the AD continuum, including Aß+ mild cognitive impairment and AD, were classified into early-onset (EO+) (<65 y old) or late-onset (LO+) (≥65 y old) groups. [18F]PI-2620 PET SUV ratios (SUVRs) were determined by calculating the cerebral-to-inferior cerebellar ratio. Cortical volumes were calculated using 3-dimensional T1-weighted MRI. The correlation between tau accumulation progression and cognitive decline was also investigated. Results: The global [18F]PI-2620 PET SUVRs were 1.04 ± 0.07 in 15 Aß- patients, 1.18 ± 0.21 in 20 LO+ patients (age, 76.7 ± 3.8 y), and 1.54 ± 0.38 in 17 EO+ patients (age, 63.4 ± 5.4 y; P < 0.001) at baseline. The global SUVR increased over 1 y by 0.05 ± 0.07 (3.90%) and 0.13 ± 0.22 (8.41%) in the LO+ and EO+ groups, respectively, whereas in the Aß- groups, it remained unchanged. The EO+ group showed higher global and regional tau deposition than did the Aß- and LO+ groups (P < 0.05 for each) and rapid accumulation in Braak stage V (0.15 ± 0.25; 9.10% ± 12.27%; P = 0.016 and 0.008), Braak stage VI (0.08 ± 0.12; 7.16% ± 10.06%; P < 0.006 and 0.005), and global SUVR (P = 0.013) compared with the Aß- group. In the EO+ group, the changes in SUVR in Braak stages II-VI were strongly correlated with the baseline and changes in verbal memory (P < 0.03). The LO+ group showed higher tau accumulation in Braak stage I-IV areas than did the Aß- group (P < 0.001 for each). In the LO+ group, the change in SUVR in Braak stages III and IV moderately correlated with the change in attention (P < 0.05), and the change in SUVR in Braak stages V and VI moderately correlated with the change in visuospatial function (P < 0.005). Conclusion: These findings suggest that [18F]PI-2620 PET can be a biomarker to provide regional and chronologic information about tau pathology in the AD continuum.

Comparison of SUVA/V and SUVA-V for Evaluating Atherosclerotic Inflammation in 18F-FDG PET/CT.

Purpose: This study aimed to compare the clinical significance of two parameters, division of standardized uptake value (SUV) of target arterial activity by background venous blood pool activity (SUVA/V) and subtraction of background venous blood pool activity from SUV of target arterial activity (SUVA-V) of carotid arteries with atherosclerotic plaques using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). Methods: Patients aged 50 years or more who were diagnosed with carotid artery stenosis of 50% or more with carotid Doppler ultrasonography and had torso 18F-FDG PET/CT were enrolled retrospectively and classified patients who developed cerebrovascular events (CVEs) within 5 years after 18F-FDG PET/CT scan as the active group and patients who did not experience the CVE within 5 years as an inactive group. We calculated SUVA/V and SUVA-V using measurements of SUVmax of carotid arteries and mean SUV of superior vena cava (SVC). Results: SUVA-V, SUVA-V_high, and SUVA-V_low were significantly higher in the active group than in the inactive group, but neither SUVA/V, SUVA/V_high, nor SUVA/V_low showed significant differences between the active and inactive groups. The difference in rank between groups of SUVA/V_high and SUVA/V_low was greater than the difference in rank between groups of SUVA-V_high and SUVA-V_low. The CVE incidence differed between SUVA/V_high and SUVA/V_low of high carotid FDG uptake, but the CVE incidence did not differ between SUVA-V_high and SUVA-V_low of high carotid FDG uptake. Conclusion: SUVA-V may be a more rational solution than SUVA/V for evaluating atherosclerotic plaque inflammation on 18F-FDG PET/CT.

Prediction of Conversion from Mild Cognitive Impairment to Alzheimer's Disease Using Amyloid PET and Brain MR Imaging Data: A 48-Month Follow-Up Analysis of the Alzheimer's Disease Neuroimaging Initiative Cohort.

We developed a novel quantification method named "shape feature" by combining the features of amyloid positron emission tomography (PET) and brain magnetic resonance imaging (MRI) and evaluated its significance in predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. From the ADNI database, 334 patients with MCI were included. The brain amyloid smoothing score (AV45_BASS) and brain atrophy index (MR_BAI) were calculated using the surface area and volume of the region of interest in AV45 PET and MRI. During the 48-month follow-up period, 108 (32.3%) patients converted from MCI to AD. Age, Mini-Mental State Examination (MMSE), cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), apolipoprotein E (APOE), standardized uptake value ratio (SUVR), AV45_BASS, MR_BAI, and shape feature were significantly different between converters and non-converters. Univariate analysis showed that age, MMSE, ADAS-cog, APOE, SUVR, AV45_BASS, MR_BAI, and shape feature were correlated with the conversion to AD. In multivariate analyses, high shape feature, SUVR, and ADAS-cog values were associated with an increased risk of conversion to AD. In patients with MCI in the ADNI cohort, our quantification method was the strongest prognostic factor for predicting their conversion to AD.

Diagnostic accuracy of 18F-FP-CIT PET for clinically uncertain Parkinsonian syndrome.

18F-FP-CIT is a high-resolution imaging marker of nigrostriatal neuronal integrity, differentiating Parkinsonism with loss of dopaminergic terminals (presynaptic Parkinsonian syndrome [PS]) from Parkinsonism without nigrostriatal degeneration (non-PS). We assessed the diagnostic accuracy of 18F-FP-CIT PET in patients with clinically uncertain PS (CUPS) at the first visit. Among the 272 patients who underwent 18F-FP-CIT PET imaging at the first visit between September 2008 and July 2012, 111 had CUPS (age, 62.6 ± 10.5 y; male:female, 45:66; symptom duration, 13.1 ± 8.8 months). Uncertainty criteria included only one of the three cardinal signs of Parkinsonism, two signs without bradykinesia, or atypical signs. The baseline clinical and 18F-FP-CIT PET imaging diagnostic accuracy was compared with the accuracy of clinical diagnosis after > 2-year follow-up. Nuclear medicine physicians assessed the 18F-FP-CIT PET images visually. Focal dopamine transporter binding deficit in the posterior putamen was considered PS. Bilateral symmetric striatum without focal deficit, suggesting normal 18F-FP-CIT PET, and focal deficits elsewhere in the striatum suggesting vascular Parkinsonism were considered non-PS. Seventy-nine patients had PS, and 32 did not. Baseline clinical diagnosis included PS in 45 patients, non-PS in 24, and inconclusive in 42. Among patients in whom initial clinical diagnosis (PS or non-PS) was possible, the sensitivity, specificity, and accuracy of the baseline clinical and 18F-FP-CIT PET imaging diagnoses were 54.4, 50.0, and 53.2%, and 98.7, 100, and 99.1%, respectively. The respective positive and negative predictive values were 95.6 and 66.7%, and 100 and 97.0%. Among those with initially inconclusive diagnosis, 64.2% were eventually diagnosed with PS while 35.7% were diagnosed with non-PS. The final clinical diagnosis of these patients all matched those made by 18F-FP-CIT PET imaging, except in one patient with scan without evidence of dopaminergic deficit (SWEDD). 18F-FP-CIT PET diagnosis was more accurate than clinical diagnosis, reducing the false-negative and inconclusive clinical diagnosis rates at baseline in patients with CUPS.

Associations of cardiovascular and diabetes-related risk factors with myocardial perfusion reserve assessed by 201Tl/99mTc-tetrofosmin single-photon emission computed tomography in patients with diabetes mellitus and stable coronary artery disease.

We aimed to examine the associations of cardiovascular risk factors with myocardial perfusion reserve (MPR) in patients with type 2 diabetes and stable coronary artery disease. The study patients were retrospectively identified from a database of patients with diabetes and stable coronary artery disease at Asan Medical Center (Seoul, Republic of Korea), covering the period from 2017 to 2019. The primary outcome variable was MPR assessed by dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT. Univariable and stepwise multivariable analyses were performed to assess the associations of cardiovascular risk factors with MPR. A total of 276 patients (236 men and 40 women) were included. The median global MPR was 2.4 (interquartile range 1.9-3.0). Seventy-five (27.2%) patients had an MPR < 2.0. Multivariable linear regression showed that smoking (ß = - 0.44, 95% confidence interval - 0.68 to - 0.21, P < 0.001), hypertension (ß = - 0.24, 95% confidence interval - 0.47 to - 0.02, P = 0.033), and summed difference score (ß = - 0.05, 95% confidence interval - 0.07 to - 0.03, P < 0.001) were independently associated with MPR. Abnormal MPR (< 2.0) was associated with a higher incidence of cardiac death or myocardial infarction (P = 0.034). MPR assessed by dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT was impaired in a large cohort of patients with diabetes. After adjusting for risk variables, including standard myocardial perfusion imaging characteristics, smoking, and hypertension were associated with MPR. Our results may aid in identifying patients with impaired MPR and stratifying patients with type 2 diabetes.

Neuroprotective Effects of Licochalcone D in Oxidative-Stress-Induced Primitive Neural Stem Cells from Parkinson's Disease Patient-Derived iPSCs.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin Ⅴ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD.

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.

The impact of subthreshold levels of amyloid deposition on conversion to dementia in patients with amyloid-negative amnestic mild cognitive impairment.

BACKGROUND: About 40-50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. METHODS: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together. RESULTS: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). CONCLUSION: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI.

[18F]THK-5351 PET Patterns in Patients With Alzheimer's Disease and Negative Amyloid PET Findings.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) does not always mean amyloid positivity. [18F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [18F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. METHODS: We performed 3.0-T magnetic resonance imaging, [18F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [18F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. RESULTS: The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [18F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13). Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [18F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. CONCLUSIONS: Approximately 70% of the patients with amyloid-negative AD showed abnormal [18F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Mortality rates of hip fracture patients with non-operative treatment.

OBJECTIVES: In this study, we aimed to analyze patient mortality rate after non-operative treatment of hip fractures to determine the distribution of causes of death and to compare factors affecting mortality. PATIENTS AND METHODS: Between January 2013 and March 2019, a total of 93 patients (17 males, 76 females; mean age: 86.0±7.4 years; range, 64 to 98 years) who had hip fractures and were treated non-operatively were analyzed retrospectively. Survival, date of death, and cause of death were collected and analyzed. Baseline demographics, pre-trauma ambulation, pre- and post-trauma residence status, American Society of Anesthesiologists Physical Status (ASA PS) classification, and Parker's mobility score were compared with one-year mortality rates. RESULTS: The mean follow-up of survivors was 16.1±11.9 (range, 6.3 to 79.6) months. The mean survival of non-survivors was 4.9±6.1 (range, 0.007 to 27.3) months. The 3-, 6-, 12-, and 24-month mortality rates were 40.9%, 53.3%, 74.4%, and 87.5%, respectively. Respiratory diseases (33.3%) and cardiovascular diseases (13.6%) were the main causes of death among the patients. There was no statistically significant difference between the patients' age, sex, fracture site, pre-trauma ambulation, pre- and post-trauma residence status, ASA PS classification, Parker's mobility score, and one-year mortality. CONCLUSION: A significant number of patients are still treated non-operatively after hip fractures, and they have a high mortality rate. Efforts and research are needed to reduce mortality and improve the quality of life.

Role of White Matter Abnormalities in the Relationship Between Microbleed Burden and Cognitive Impairment in Cerebral Amyloid Angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline. OBJECTIVE: We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA. METHODS: This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aß+ CAA) and patients with Alzheimer's disease (Aß+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition. RESULTS: We analyzed 30 patients with Aß+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aß+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aß+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aß+ AD group(family-wise error-corrected p < 0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition. CONCLUSION: This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA.

18F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in ß-Amyloid-Negative Amnestic Mild Cognitive Impairment.

PURPOSE: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer's disease-type tau aggregates. ß-amyloid (Aß)-negative (Aß-) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer's disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aß- aMCI patients. MATERIALS AND METHODS: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aß- aMCI patients. RESULTS: Among the 25 Aß- aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). CONCLUSION: The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aß- aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

60 Years of Achievements by KSNM in Neuroimaging Research.

Nuclear medicine neuroimaging is able to show functional and molecular biologic abnormalities in various neuropsychiatric diseases. Therefore, it has played important roles in the clinical diagnosis and in research on the normal and pathological states of the brain. More than 400 outstanding studies have been conducted by Korean researchers over the past 60 years. In the 1990s, when multiheaded single-photon emission computed tomography (SPECT) scanners were first introduced in South Korea, stroke research using brain perfusion SPECT was conducted. With the spread of positron emission tomography (PET) scanners in the 2000s, research on the clinical usefulness of PET and the evaluation of pathophysiology in various diseases such as epilepsy, brain tumors, degenerative brain diseases, and other neuropsychiatric diseases were actively conducted using [18F]FDG and various neuroreceptor tracers. In the 2010s, with the clinical application of new radiopharmaceuticals for amyloid and tau imaging, research demonstrating the clinical usefulness of PET imaging and the pathophysiology of dementia has increased rapidly. It is expected that the role of nuclear medicine will expand with the development of new radiopharmaceuticals and analysis technologies, along with the application of artificial intelligence for early and differential diagnosis, and the development of therapeutic agents for degenerative brain diseases.

PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma.

PURPOSE: This work aimed to explore in depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in PET and to identify therapeutic targets based on this imaging-genomic surrogate. EXPERIMENTAL DESIGN: We used RNA sequencing and whole-exome sequencing data obtained from 117 patients with HCC who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG-non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo. RESULTS: High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models. CONCLUSIONS: Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of patients with HCC.

Crossed Hemispheric Accumulation of ß-Amyloid and Tau Protein in a Patient With Typical Alzheimer Disease.

Amyloid (Aß) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aß and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aß and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aß and tau pathogenic pathways in AD.

Clinical Implications of Amyloid-Beta Accumulation in Occipital Lobes in Alzheimer's Continuum.

A substantial amount of amyloid-beta (Aß) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aß accumulation in the occipital lobes in the Alzheimer's disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aß positive patients were divided into occipital Aß positive (OCC+) and occipital Aß negative (OCC-) groups based on Aß accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC- group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey-Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aß positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum.

Comparison of empagliflozin and sitagliptin therapy on myocardial perfusion reserve in diabetic patients with coronary artery disease.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors reduce the risk of cardiovascular events in type 2 diabetic patients with coronary artery disease (CAD); however, the underlying mechanisms remain unclear. OBJECTIVES: We compared the effects of empagliflozin vs. sitagliptin therapy on myocardial perfusion reserve (MPR) using dynamic single-photon emission computed tomography (SPECT) imaging. METHODS: In total, 100 patients with type 2 diabetes, CAD and an MPR <2.5 were randomized to receive either empagliflozin (10 mg once daily) or sitagliptin (100 mg once daily). Dynamic SPECT examinations were performed at baseline and at 6 months. The primary endpoint was the percent change of global MPR. Evaluable SPECT data were available for 98 patients. RESULTS: Baseline clinical characteristics and SPECT data were well balanced between the two groups. At a 6-month follow-up, the fasting glucose and glycated hemoglobin levels significantly decreased in both groups. Hematocrit and hemoglobin levels significantly increased in the empagliflozin group but not in the sitagliptin group. The global MPR significantly improved after treatment in both groups (34.5 ± 70.6%; P = 0.005 for empagliflozin vs. 22.4 ± 45.7%; P = 0.024 for sitagliptin). However, there was no significant difference in the global MPR between the two groups (P = 0.934). Similar findings were detected with regard to the regional MPR. CONCLUSION: Among patients with type 2 diabetes and CAD, both empagliflozin and sitagliptin significantly improved the global MPR with no significant difference between the groups.

Metabolic activity by FDG-PET/CT after neoadjuvant chemotherapy in borderline resectable and locally advanced pancreatic cancer and association with survival.

BACKGROUND: The optimal prognostic markers for neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer are not yet established. METHOD: Patients who received neoadjuvant chemotherapy prior to surgery and underwent FDG-PET/CT between July 2012 and December 2017 were included. Metabolic parameters including standardized uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) on PET/CT, and response evaluations using PERCIST criteria, were investigated for its impact on survival and recurrence. Cox proportional hazards model was performed. Differences in risk were expressed as hazard ratio (HR) with 95 per cent confidence interval. RESULTS: The patients with borderline resectable (N = 106) or locally advanced pancreatic cancer (N = 82) were identified. The median survival was 33.6 months. Decreased metabolic parameters of PET/CT after neoadjuvant chemotherapy were associated with positive impacts on survival and recurrence such as SUVmax (HR 1.16, 95 per cent c.i. 1.01 to 1.32, P = 0.025), SUVpeak (HR 1.26, 95 per cent c.i. 1.05 to 1.51, P = 0.011), and MTV (HR 1.15, 95 per cent c.i. 1.04 to 1.26, P = 0.005). Large delta values were related to a positive impact on recurrence such as SUVmax (HR 1.21, 95 per cent c.i. 1.06 to 1.38, P = 0.005). Post-neoadjuvant chemotherapy SUVmax ≥3 (HR 3.46, 95 per cent c.i. 1.21 to 9.91; P = 0.036) was an independent prognostic factor for negative impact on survival. Patients with post-neoadjuvant chemotherapy SUVmax <3 showed more chemotherapy cycles (8.7 versus 6.2, P = 0.001), more frequent complete metabolic response (25 versus 2.2 per cent, P = 0.002), smaller tumour size (2.1 versus 3.1 cm, P = 0.002), and less frequent lymphovascular invasion (23.7 versus 51.1 per cent, P = 0.020) than patients with SUVmax ≥3. CONCLUSION: Reduction in metabolic tumour parameters of FDG- PET/CT after neoadjuvant chemotherapy indicates improved overall survival and recurrence-free survival.

Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism.

Delayed phase 18F-FP-CIT PET (dCIT) can assess the striatal dopamine transporter binding to detect degenerative parkinsonism (DP). Early phase 18F-FP-CIT (eCIT) can assess the regional brain activity for differential diagnosis among parkinsonism similar with 18F-FDG PET. We evaluated the diagnostic performance of dual phase 18F-FP-CIT PET (dual CIT) and 18F-FDG PET compared with clinical diagnosis in 141 subjects [36 with idiopathic Parkinson's disease (IPD), 77 with multiple system atrophy (MSA), 18 with progressive supranuclear palsy (PSP), and 10 with non-DP)]. Visual assessment of eCIT, dCIT, dual CIT, 18F-FDG and 18F-FDG PET with dCIT was in agreement with the clinical diagnosis in 61.7%, 69.5%, 95.7%, 81.6%, and 97.2% of cases, respectively. ECIT showed about 90% concordance with non-DP and MSA, and 8.3% and 27.8% with IPD and PSP, respectively. DCIT showed ≥ 88% concordance with non-DP, IPD, and PSP, and 49.4% concordance with MSA. Dual CIT showed ≥ 90% concordance in all groups. 18F-FDG PET showed ≥ 90% concordance with non-DP, MSA, and PSP, but only 33.3% concordance with IPD. The combination of 18F-FDG and dCIT yielded ≥ 90% concordance in all groups. Dual CIT may represent a powerful alternative to the combination of 18F-FDG PET and dCIT for differential diagnosis of parkinsonian disorders.