Graph Neural Network Model for Prediction of Non-Small Cell Lung Cancer Lymph Node Metastasis Using Protein-Protein Interaction Network and 18F-FDG PET/CT Radiomics.

The image texture features obtained from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images of non-small cell lung cancer (NSCLC) have revealed tumor heterogeneity. A combination of genomic data and radiomics may improve the prediction of tumor prognosis. This study aimed to predict NSCLC metastasis using a graph neural network (GNN) obtained by combining a protein-protein interaction (PPI) network based on gene expression data and image texture features. 18F-FDG PET/CT images and RNA sequencing data of 93 patients with NSCLC were acquired from The Cancer Imaging Archive. Image texture features were extracted from 18F-FDG PET/CT images and area under the curve receiver operating characteristic curve (AUC) of each image feature was calculated. Weighted gene co-expression network analysis (WGCNA) was used to construct gene modules, followed by functional enrichment analysis and identification of differentially expressed genes. The PPI of each gene module and genes belonging to metastasis-related processes were converted via a graph attention network. Images and genomic features were concatenated. The GNN model using PPI modules from WGCNA and metastasis-related functions combined with image texture features was evaluated quantitatively. Fifty-five image texture features were extracted from 18F-FDG PET/CT, and radiomic features were selected based on AUC (n = 10). Eighty-six gene modules were clustered by WGCNA. Genes (n = 19) enriched in the metastasis-related pathways were filtered using DEG analysis. The accuracy of the PPI network, derived from WGCNA modules and metastasis-related genes, improved from 0.4795 to 0.5830 (p < 2.75 × 10-12). Integrating PPI of four metastasis-related genes with 18F-FDG PET/CT image features in a GNN model elevated its accuracy over a without image feature model to 0.8545 (95% CI = 0.8401-0.8689, p-value < 0.02). This model demonstrated significant enhancement compared to the model using PPI and 18F-FDG PET/CT derived from WGCNA (p-value < 0.02), underscoring the critical role of metastasis-related genes in prediction model. The enhanced predictive capability of the lymph node metastasis prediction GNN model for NSCLC, achieved through the integration of comprehensive image features with genomic data, demonstrates promise for clinical implementation.

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Patients Using Harmonized Radiomics of Multcenter 18F-FDG-PET Image.

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

The role of 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma after radioimmunotherapy using 131I-rituximab as consolidation therapy.

PURPOSE: To evaluate the prognostic value of pretreatment 18F-FDG PET/CT after consolidation therapy of 131I-rituximab in patients with diffuse large B-cell lymphoma (DLBCL) who had acquired complete remission after receiving chemotherapy. METHODS: Patients who were diagnosed with DLBCL via histologic confirmation were retrospectively reviewed. All patients had achieved complete remission after 6 to 8 cycles of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) chemotherapy after which they underwent consolidation treatment with 131I-rituximab. 18F-FDG PET/CT scans were performed before R-CHOP for initial staging. The largest diameter of tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment 18F-FDG PET/CT scans. Receiver-operating characteristic curves analysis was introduced for assessing the optimal criteria. Kaplan-Meier curve survival analysis was performed to evaluate both relapse free survival (RFS) and overall survival (OS). RESULTS: A total of 15 patients (12 males and 3 females) with a mean age of 56 (range, 30-73) years were enrolled. The median follow-up period of these patients was 73 months (range, 11-108 months). Four (27%) patients relapsed. Of them, three died during follow-up. Median values of the largest tumor size, highest SUVmax, MTV, and TLG were 5.3 cm (range, 2.0-16.4 cm), 20.2 (range, 11.1-67.4), 231.51 (range, 15-38.34), and 1277.95 (range, 238.37-10341.04), respectively. Patients with SUVmax less than or equal to 16.9 showed significantly worse RFS than patients with SUVmax greater than 16.9 (5-year RFS rate: 60% vs. 100%, p = 0.008). Patients with SUVmax less than or equal to 16.9 showed significantly worse OS than patients with SUVmax greater than 16.9 (5-year OS rate: 80% vs. 100% p = 0.042). CONCLUSION: Higher SUVmax at pretreatment 18F-FDG PET/CT was associated with better relapse free survival and overall survival in DLBCL patients after consolidation therapy with 131I-rituximab. However, because this study has a small number of patients, a phase 3 study with a larger number of patients is needed for clinical application in the future.

The Prediction of HER2-Targeted Treatment Response Using 64Cu-Tetra-Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report.

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status. 64Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64Cu-DOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.

Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause.

Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor; thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.

Implication of FDG-PET/CT without synchronous colonic lesion in patients with stenotic left-sided colorectal cancer.

Although 18-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for detecting synchronous colorectal cancer (CRC) in stenotic CRC, long-term outcomes of patients without synchronous FDG-avid lesions are not well reported. We investigated postoperative colonoscopy results in patients with left-sided stenosing CRC without synchronous FDG-avid lesions. In this retrospective review, 754 patients with left-sided CRC without synchronous FDG-avid lesions on preoperative 18F-FDG PET/CT were divided into two groups based on the completeness of preoperative colonoscopy. Propensity score matching was performed to balance baseline characteristics. Results of postoperative colonoscopy were compared in both the unmatched and matched cohorts. At 1 and 5 years after surgery, the cumulative risk of advanced adenoma (AA) or carcinoma (CA) in all patients, risk of CA, and additional surgical risk were 1.8% and 10.1%, 0.1% and 0.4%, and 0% and 0.5%, respectively. In both cohorts, the AA risk was significantly higher in the incomplete colonoscopy group. However, the risk of CA showed no between-group difference in the matched cohort. Additional surgical risk did not differ between the two groups. Thus, the finding of negative FDG-avid lesions in the proximal colon in addition to the target CRC ensures the absence of additional lesions warranting surgical plan changes.

Sulforaphane enhances long-term potentiation and ameliorate scopolamine-induced memory impairment.

Increases in human life expectancy have led to increases in the prevalence of senile dementia and neurodegenerative diseases. This is a major problem because there are no curative treatments for these diseases, and patients with unmanaged cognitive and neurodegenerative symptoms experience many social problems. Sulforaphane is a type of organosulfur compound known as an isothiocyanate. It is derived from glucoraphanin, a compound found in cruciferous vegetables such as broccoli, brussels sprouts, and cabbages, via an enzymatic reaction that is triggered by plant damage (e.g., chewing). Sulforaphane exhibits activity against cancer, inflammation, depression, and severe cardiac diseases. It can also alleviate oxidative stress and neural dysfunction in the brain. However, there is insufficient knowledge about the electrophysiological and behavioral basis of the effects of sulforaphane on learning and memory. Therefore, we evaluated whether acute sulforaphane administration affected long-term potentiation (LTP) in organotypic cultured rat hippocampal tissues. We also measured the effect of sulforaphane on the performance of three behavioral tests, the Y-maze test, the passive avoidance test, and the Morris water maze, which assess short-term memory, avoidance memory, and short and long-term spatial memory, respectively. We found that sulforaphane increased the total field excitatory postsynaptic potential (fEPSP) in a dose-dependent manner after high frequency stimulation and attenuated scopolamine-induced interference of the fEPSP in the hippocampal CA1 area. Sulforaphane also restored cognitive function and inhibited memory impairment as indicated by the alleviation of the negative neurological effects of scopolamine, i.e, a lowered ratio of spontaneous alternation in the Y-maze, a reduced step-through latency in the passive avoidance test, and an increased navigation time in the Morris water maze. These results indicate that sulforaphane can effectively prevent the attenuation of LTP and cognitive abilities induced by cholinergic and muscarinic receptor blockade. Further research is warranted to explore the potential therapeutic and prophylactic utility of sulforaphane for improving learning and memory, especially in those suffering from neurodegenerative disorders.

A Phase 0 Microdosing PET/CT Study Using O-[18F]Fluoromethyl-d-Tyrosine in Normal Human Brain and Brain Tumor.

PURPOSE: The aim of the present study was to obtain information about distribution, radiation dosimetry, toxicity, and pharmacokinetics of O-[18F]fluoromethyl-d-tyrosine (d-18F-FMT), an amino acid PET tracer, in patients with brain tumors. PATIENTS AND METHODS: A total of 6 healthy controls (age = 19-25 years, 3 males and 3 females) with brain PET images and radiation dosimetry and 12 patients (median age = 60 years, 6 males and 6 females) with primary (n = 5) or metastatic brain tumor (n = 7) were enrolled. We acquired 60-minute dynamic brain PET images after injecting 370 MBq of d-18F-FMT. Time-activity curves of d-18F-FMT uptake in normal brain versus brain tumors and tumor-to-background ratio were analyzed for each PET data set. RESULTS: Normal cerebral uptake of d-18F-FMT decreased from 0 to 5 minutes after injection, but gradually increased from 10 to 60 minutes. Tumoral uptake of d-18F-FMT reached a peak before 30 minutes. Tumor-to-background ratio peaked at less than 15 minutes for 8 patients and more than 15 minutes for 4 patients. The mean effective dose was calculated to be 13.2 µSv/MBq. CONCLUSIONS: Using d-18F-FMT as a PET radiotracer is safe. It can distinguish brain tumor from surrounding normal brain tissues with a high contrast. Early-time PET images of brain tumors should be acquired because the tumor-to-background ratio tended to reach a peak within 15 minutes after injection.

A preliminary clinical trial to evaluate 64Cu-NOTA-Trastuzumab as a positron emission tomography imaging agent in patients with breast cancer.

BACKGROUND: The purpose of this study was to evaluate both the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer. METHODS: PET images at 1, 24, and 48 h after 296 MBq of 64Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors' and metastatic lesions' maximum standardized uptake value (SUVmax) was evaluated. The mean SUVmax (SUVmean) was evaluated in the other organs, including the blood pool, liver, kidney, muscle, spleen, bladder, and the lungs, as well as the bones. Moreover, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed based on feedback regarding adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration. RESULTS: 64Cu-NOTA-Trastuzumab PET images showed that the overall SUVmean values in each organ negatively correlated with time. The liver's average SUVmean values were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 h, 24 h, and 48 h after injection, respectively. The average SUVmean blood values were measured at 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 h, 24 h, and 48 h after injection, respectively. The SUVmax of HER2-positive tumors was relatively higher than HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 h after injection, respectively). Tumor-to-background ratios were higher in the HER2-positive tumors than in the HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq). CONCLUSIONS: 64Cu-NOTA-Trastuzumab showed a specific uptake at the HER2-expressing tumors, thus making it a feasible and safe monitoring tool of HER2 tumor status in patients with breast cancer. TRIAL REGISTRATION: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr.

A microdose clinical trial to evaluate [18F]Florastamin as a positron emission tomography imaging agent in patients with prostate cancer.

PURPOSE: To evaluate the biodistribution of [18F]Florastamin, a novel 18F-labelled positron emission tomography (PET) tracer for prostate-specific membrane antigen (PSMA) for the diagnosis of prostate cancer. METHODS: PET was performed for five healthy controls and 10 patients with prostate cancer at 0, 10, 30, 70, and 120 mins after injecting 370 MBq of [18F]Florastamin. The maximum standardised uptake value (SUVmax) was evaluated in the primary tumour. The mean SUVmax (SUVmean) was evaluated in normal organs. Furthermore, the residence time was evaluated by assessing radioactivity in each organ. The internal radiation dosimetry was calculated using the OLINDA/EXM software. RESULTS: The SUVmax in primary tumours increased with time. A favourable tumour to background ratio was also observed over time. Multiple lymph nodes and bone metastases were also evaluated and showed a similar pattern to SUVmax in the primary tumour. In one patient, a tiny lymph node metastasis was identified using [18F]Florastamin PET, which was not observed using other modalities, and was histologically confirmed. The highest absorbed dose was observed in the kidney (0.062 ± 0.015 mGy/MBq), followed by the bladder (0.032 ± 0.013 mGy/MBq), liver (0.022 ± 0.006 mGy/MBq), and salivary gland (0.018 ± 0.006 mGy/MBq). The effective dose with a 370 MBq injection of [18F]Florastamin was 1.81 mSv. No adverse events related to [18F]Florastamin were reported. CONCLUSION: We identified a novel PSMA-targeted PET ligand, [18F]Florastamin, for imaging prostate cancer. [18F]Florastamin showed a high SUVmax and relatively high tumour to background ratio in both primary tumour and metastatic lesions, which suggests its high sensitivity to detect tumours without any adverse events. TRIAL REGISTRATION: KCT0003924 registered at https://cris.nih.go.kr/ .

Early prediction of neoadjuvant chemotherapy response for advanced breast cancer using PET/MRI image deep learning.

This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26-66) years]. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained with the corresponding baseline values (SUV0, MTV0, and TLG0, respectively) and interim PET images (SUV1, MTV1, and TLG1, respectively). Mean apparent diffusion coefficients were obtained from baseline and interim diffusion MR images (ADC0 and ADC1, respectively). The differences between the baseline and interim parameters were measured (ΔSUV, ΔMTV, ΔTLG, and ΔADC). Subgroup analysis was performed for the HER2-negative and triple-negative groups. Datasets for convolutional neural network (CNN), assigned as training (80%) and test datasets (20%), were cropped from the baseline (PET0, MRI0) and interim (PET1, MRI1) images. Histopathologic responses were assessed using the Miller and Payne system, after three cycles of chemotherapy. Receiver operating characteristic curve analysis was used to assess the performance of the differentiating responders and non-responders. There were six responders (11%) and 50 non-responders (89%). The area under the curve (AUC) was the highest for ΔSUV at 0.805 (95% CI 0.677-0.899). The AUC was the highest for ΔSUV at 0.879 (95% CI 0.722-0.965) for the HER2-negative subtype. AUC improved following CNN application (SUV0:PET0 = 0.652:0.886, SUV1:PET1 = 0.687:0.980, and ADC1:MRI1 = 0.537:0.701), except for ADC0 (ADC0:MRI0 = 0.703:0.602). PET/MRI image deep learning model can predict pathological responses to NAC in patients with advanced breast cancer.

The correlation of neuropsychological evaluation with 11C-PiB and 18F-FC119S amyloid PET in mild cognitive impairment and Alzheimer disease.

For the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), variable neuroimaging and neuropsychological tests have been used. We aimed to evaluate the correlation of neuropsychological domain with new amyloid positron emission tomography (PET) study and to validate the availability of new PET tracer.We enrolled 20 patients who underwent C-PiB-PET/CT, new PET tracer F-FC119S PET/CT from November, 2014 to July, 2015. Among them, 10 patients were diagnosed with AD and 10 patients with MCI. The current version of Seoul Neuropsychological Screening Battery (SNSB) II was performed for cognitive evaluation. Each parameter of SNSB was compared between 2 patient groups. Spearman correlation analysis between value of SNSB domain and standardized uptake value ratio (SUVR) of PET was also performed.The AD group presented significant poor z-score in Korean-Boston Naming Test(K-BNT) (P = .01),copy score of Rey Complex Figure Test (RCFT) (P = .049), immediate (P = .028)and delayed memory of Seoul Verbal Learning Test (SVLT) (P = .028), recognition of RCFT (P = .004), "animal" of Controlled Oral Word Association Test (COWAT) (P = .041), color reading of Korean-Color Word Stroop test (K-CWST) (P = .014), and Digit Symbol Coding (DSC) (P = .007) compared with MCI group. That means, except attention domain, all other cognitive domains were relatively impaired in AD compared with MCI. In correlation analysis, we found that poor performances on copy score of RCFT in MCI groups were associated with great beta amyloid burden in frontal area in both C-PiB-PET/CT and F-FC119S PET/CT. In AD group, F-FC119S PET presented more extensive correlation in each cognitive domain with multiple cortical areas compared with C-PiB-PET.The degree of amyloid burden assessed on F-FC119S PET was significantly correlated with neuropsychological test in AD, and also MCI patients. The combination of neuropsychological evaluation with novel F-FC119S PET/CT can be used for valid biomarker for MCI and AD.

Clinical Usefulness of 18F-FC119S Positron-Emission Tomography as an Auxiliary Diagnostic Method for Dementia: An Open-Label, Single-Dose, Evaluator-Blind Clinical Trial.

BACKGROUND AND PURPOSE: The aim of this study was to determine the diagnostic performance and safety of a new ¹8F-labeled amyloid tracer, ¹8F-FC119S. METHODS: This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹8F-FC119S PET, ¹8F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹8F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹8F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored. RESULTS: Visual assessments of the ¹8F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹8F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹8F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods. CONCLUSIONS: ¹8F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.

Early response monitoring of neoadjuvant chemotherapy using [18F]FDG PET can predict the clinical outcome of extremity osteosarcoma.

BACKGROUND: To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. METHODS: A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). RESULTS: A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25-34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47-24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16-30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over - 39.8% or Δ%SUV02 over - 54.1% showed worse EFS rates than others (p < 0.05). CONCLUSIONS: PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

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

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

Comparisons of 131I-rituximab treatment responses in patients with aggressive lymphoma and indolent lymphoma.

OBJECTIVE: We evaluated the changes in treatment response over time after single 131I-rituximab radioimmunotherapy (RIT) according to non-Hodgkin lymphoma (NHL) types. METHODS: Fifteen aggressive and 21 indolent lymphoma cases undergoing RIT were evaluated. All patients underwent 18F-FDG-PET-CT before and 5 days, 1, and 3 months after RIT. The maximum standardized uptake value (SUV) and the sum of the products of the longest perpendicular diameters of tumours (SPD) were evaluated. Treatment responses were evaluated 1 and 3 months after RIT RESULTS: In aggressive lymphoma, SUV decreased at 5 days after RIT but increased after that. SPD decreased at 1 month but significantly increased at 3 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) at 1 month after RIT were changed to PD at 3 months after RIT. In indolent lymphoma, the SUV decreased continuously until 1 month after RIT. The SPD significantly decreased at 1 month and tended to further decrease to 3 months. CR, PR, SD, and PD at 1 month after RIT were achieved in 0, 8, 13, and 0 cases, respectively. Among the 13 SD cases, one changed to CR, three changed to PR, and nine had not changed at 3 months after RIT. CONCLUSIONS: The treatment response to single RIT differed depending on NHL type. These findings suggest a need to establish an optimal treatment regimen based on NHL aggressiveness.

Design of High Corrosion Resistant Ni Alloy Using Electronic State Calculation.

Ni alloys are used as the prominent industrial material for heat-resistance and corrosion-resistance. Out of them, Inconel has excellent properties for high-temperature heat-resistant equipment as an excellent material for equipment such as ultrahigh-temperature electric furnace and or boiler. However, Ni alloys used in various areas contain high-priced metals such as Ta, Nb, or Re and their use have been limited to industrial sector so far due to the price incompetence. In this study, the alloy Ni-28Cr-4Mo-2Ti was designed by electronic state calculation by replacing the expensive material of Ta and Nb in Inconel 625 with Ti. In order to compare the corrosion properties, they were intentionally corroded in a furnace at 500 °C for 3 months and potentiodynamic polarization method was used to check the corrosion rate. The validity of the results was also confirmed by using the values of atomic radius and electronegativity. As a result, it was confirmed that the newly designed alloy had superior corrosion resistance at higher temperature than Inconel 625.

An enhanced treatment effect can be expected from a higher serum thyroglobulin level after radioactive iodine therapy.

OBJECTIVE: The aim of this study was to investigate if increased serum thyroglobulin (Tg) levels after radioactive iodine (RAI) showed more therapeutic effects in patients with differentiated thyroid cancer (DTC). METHODS: Data of 65 patients with DTC who underwent RAI from June 2014 to September 2016 were reviewed. Serum thyroglobulin was measured immediately before (Tg1) and 48 h (Tg2) after RAI under TSH stimulation. Differences and ratios between serum Tg measurements (DeltaTg = Tg2 - Tg1 and RatioTg = Tg2/Tg1) were calculated. The treatment response of distant metastasis was assessed using the RECIST criteria. RESULTS: There was no difference in the median values of Tg1 and Tg2 (2.6 [range, 0.7-1957.5] ng/mL vs. 7.4 [range, 0.7-5276.0] ng/mL, p = 0.240) in all patients (73 scans, 65 patients). In subgroup analysis, Tg levels increased slightly in patients with distant metastasis (8 scans, 7 patients) (Tg1 vs. Tg2; 48.9 [range, 2.4-1957.5] ng/mL vs. 63.2 [range, 4.4-5276.0] ng/mL, p = 0.408). Among patients with distant metastasis, one patient with a partial response to treatment had a more than 4000fold increase in Tg levels and one patient with stable disease showed a 20fold increase in Tg levels. In contrast, five patients with disease progression showed only two to eightfold increase or more than 100fold decrease in Tg levels at 48 h after RAI. However, there was a significant increase in serum Tg levels in patients without distant metastasis (65 scans, 58 patients) after RAI (Tg1 vs. Tg2; 2.0 [range, 0.7-141.9] ng/mL vs. 6.8 [range, 0.7-577.7] ng/mL, p = 0.026). CONCLUSIONS: A higher elevation of Tg levels after RAI may be associated with a better treatment outcome in DTC patients with distant metastasis. An increase in Tg levels after RAI may reflect the destruction of cancer and thyroid cells.