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.

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.

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/ .

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.

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.

Head-to-head comparison of 18 F-FP-CIT and 123 I-FP-CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study.

123 I-FP-CIT and 18 F-FP-CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head-to-head comparisons between 123 I-FP-CIT and 18 F-FP-CIT. Therefore, in this study, 123 I-FP-CIT SPECT/CT was compared with 18 F-FP-CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT. Visual analysis showed that the striatal uptake of both radiotracers was decreased in the PD group, whereas striatal uptake was intact in the ET group. The SBR between 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on 18 F-FP-CIT PET/CT were higher than those on 123 I-FP-CIT SPECT/CT (2.19 ± .87 and 1.22 ± .49, respectively; p < .01). The PCRs in these two modalities were correlated with each other (r = .71, p < .01). The mean PCRs on 18 F-FP-CIT PET/CT were not significantly higher than those on 123 I-FP-CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both 123 I-FP-CIT and 18 F-FP-CIT was decreased in the PD group when compared with the ET controls. Visual analyses using both methods did not affect the diagnostic accuracy in this study. However, semiquantitative analysis indicated a better contrast of 18 F-FP-CIT PET/CT relative to 123 I-FP-CIT SPECT/CT.

Evaluation of [(89)Zr]-Oxalate as a PET Tracer in Inflammation, Tumor, and Rheumatoid Arthritis Models.

To obtain an additional pharmacological agent for the diagnosis of inflammation, we investigated the medical use of (89)Zr-oxalate as a positron emission tomography (PET) probe for the in vivo imaging of inflammation and compared its efficacy to that of 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and sodium [(18)F]fluoride. (89)Zr-oxalate exhibited observable higher uptake in a macrophage cell line than in tumor cells. The inflammatory lesions and tumors were clearly visualized by PET imaging and autoradiography using (89)Zr-oxalate. Compared to [(18)F]FDG and sodium [(18)F]fluoride, (89)Zr-oxalate demonstrated a high selectivity index to the tumor at an early time point after injection and to inflammation at a delayed time point after injection (24 h). Through histological examination, large numbers of macrophages and neutrophils were observed in the tumor lesions with the highest (89)Zr-oxalate uptake. In a rheumatoid arthritis (RA) mouse model, (89)Zr-oxalate demonstrated a high level of accumulation in inflammatory lesions. (89)Zr-oxalate is a new strategic tool for tumor imaging and inflammatory processes.

Radiological Justification for and Optimization of Nuclear Medicine Practices in Korea.

Nuclear medicine is a rapidly growing discipline that employs advanced novel hybrid techniques that provide unique anatomical and functional information, as well as targets for molecular therapy. Concomitantly, there has been an increase in the attention paid to medical radiation exposure. A radiological justification for the practice of nuclear medicine has been implemented mainly through referral guidelines based on research results such as prospective randomized clinical trials. The International Commission on Radiological Protection recommends diagnostic reference levels as a practical mechanism to optimize medical radiation exposure in order to be commensurate with the medical purpose. The Korean Society of Nuclear Medicine has been implementing radiological optimization through a survey of the protocols on how each hospital determines the dose of administration of each radiopharmaceutical. In the case of nuclear medicine, radiation exposure of caregivers and comforters of patients discharged after administration of therapeutic radiopharmaceuticals can occur; therefore, optimization has been implemented through written instructions for patients, based on international recommendations. The development of patient-radiation-dose monitoring software, and a national registry and management system of patient-radiation-dose is needed to implement radiological optimization through diagnostic reference levels. This management system must work in agreement with the "Institute for Quality Management of Nuclear Medicine", and must take into account the medical reality of Korea, such as low medicine fee, in order to implement reasonable radiological justification and optimization.

Prognostic value of 18F-FDG uptake by regional lymph nodes on pretreatment PET/CT in patients with resectable colorectal cancer.

PURPOSE: We evaluated the ability of pretreatment (18)F-FDG uptake by regional lymph nodes to predict the survival of patients with resectable colorectal cancer. METHODS: The records of 78 patients with AJCC stage III colorectal cancer (pathologically confirmed node-positive disease without evidence of distant metastasis) treated with surgery and adjuvant chemotherapy were retrospectively reviewed. The maximum standardized uptake values of the primary tumor (SUVp) and regional lymph nodes (SUVn) were measured by pretreatment (18)F-FDG PET/CT. The ROC curve analyses and the Cox proportional hazard model were used to analyze whether SUVp, SUVn, and clinicopathologic parameters could predict disease-free survival. RESULTS: Although there were no significant differences between the median SUVp in the event group and that in the non-event group, the median SUVn was significantly higher in the event group (1.7) than in the non-event group (0.8, p = 0.023). Based on the ROC curve analysis, SUVn predicted the event for disease-free survival (AUC = 0.668, p = 0.02) with the optimal criterion, sensitivity, specificity, and accuracy of > 1.2, 71%, 63%, and 65%, respectively. However, SUVp did not predict disease-free survival (AUC = 0.570, p = 0.349). Univariate analysis revealed that SUVn (p = 0.011) and venous invasion (p = 0.016) were associated with disease-free survival, but pathologic N stage was not (p = 0.09). By multivariate analysis, only SUVn > 1.2 independently shortened the disease-free survival (relative risk, 2.97; 95% CI, 1.14-7.74, p = 0.026). CONCLUSION: SUVn before surgery may be a useful prognostic marker in patients with AJCC stage III colorectal cancer.

Early response monitoring to neoadjuvant chemotherapy in osteosarcoma using sequential ¹8F-FDG PET/CT and MRI.

PURPOSE: We evaluated the potential of sequential fluorine-18 fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET)/computed tomography (CT) and MRI (PET/MRI) after one cycle of neoadjuvant chemotherapy to predict a poor histologic response in osteosarcoma. METHODS: A prospective study was conducted on 30 patients with osteosarcoma treated with two cycles of neoadjuvant chemotherapy and surgery. All patients underwent PET/MRI before, after one cycle, and after the completion of neoadjuvant chemotherapy, respectively. Imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor volume based on magnetic resonance (MR) images (MRV)] and their % changes were calculated on each PET/MRI data set, and histological responses were evaluated on the postsurgical specimen. RESULTS: A total of 17 patients (57%) exhibited a poor histologic response after two cycles of chemotherapy. Unlike the little volumetric change in MRI, PET parameters significantly decreased after one and two cycles of chemotherapy, respectively. After one cycle of chemotherapy, SUVmax, MTV, and TLG predicted the poor responders. Among these parameters, either MTV ≥ 47 mL or TLG ≥ 190 g after one cycle of chemotherapy was significantly associated with a poor histologic response on multivariate logistic regression analysis (OR 8.98, p = 0.039). The sensitivity, specificity, and accuracy of these parameters were 71%, 85% and 77%; and 71%, 85% and 77 %, respectively. CONCLUSION: The histologic response to neoadjuvant chemotherapy in osteosarcoma can be predicted accurately by FDG PET after one course of chemotherapy. Among PET parameters, MTV and TLG were independent predictors of the histologic response.

Sildenafil alleviates bronchopulmonary dysplasia in neonatal rats by activating the hypoxia-inducible factor signaling pathway.

Bronchopulmonary dysplasia (BPD) is a major cause of morbidity in premature infants receiving oxygen therapy. Currently, sildenafil is being examined clinically to improve pulmonary function in patients with BPD. Based on the pharmacological action of sildenafil, the elevation of cyclic guanosine 3',5'-monophosphate (cGMP) in lung tissue is considered to underlie its beneficial effects, but this mechanism is not understood at the molecular level. Here, we examined the possibility that sildenafil helps the pulmonary system adapt to hyperoxic stress. To induce BPD, fetal rats were exposed to LPS before delivery, and neonates were exposed to hyperoxia, followed by intraperitoneal injections of sildenafil. Alveolarization was impaired in rats exposed to hyperoxia, and alveolarization significantly recovered with sildenafil. An immunohistochemical examination revealed that sildenafil effectively increased vascular distribution in lung tissue. Furthermore, the oxygen sensor hypoxia-inducible factor (HIF)-1/2α and the angiogenic factor vascular endothelial growth factor (VEGF) were highly expressed in the lungs of sildenafil-treated rats. In human small-airway epithelial cells, HIF-1/2α and its downstream genes, including VEGF, were confirmed to be induced by sildenafil at both the protein and mRNA levels. Mechanistically, cGMP in airway cells accumulated after sildenafil treatment because of interfering phosphodiesterase Type 5, and subsequently cGMP activated HIF-mediated hypoxic signaling by stimulating the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog 1 (AKT)-mammalian target of rapamycin (mTOR) pathway. This study provides a better understanding about the mode of action for sildenafil, and suggests that HIF can be a potential target for treating patients with BPD.

Prognostic significance of pretreatment ¹8F-FDG PET/CT in patients with relapsed/refractory B-cell non-Hodgkin's lymphoma treated by radioimmunotherapy using ¹³¹I-rituximab.

AIMS: It was the aim of this paper to identify prognostic factors in patients with relapsed or refractory B-cell non-Hodgkin's lymphomas, treated by radioimmunotherapy (RIT) with radioiodinated human/murine chimeric anti-CD20 monoclonal antibody rituximab (¹³¹I-rituximab). METHODS: Twenty-four patients were enrolled prospectively and were treated with unlabeled rituximab 70 mg and a therapeutic activity (median 7.3 GBq) of ¹³¹I-rituximab. Contrast-enhanced ¹8F-FDG PET/CT scans were performed before and after 1 month of RIT. Tumor sizes and maximum standardized uptake values (SUVmax) of scans were measured. RESULTS: Four of the 24 patients survived. High SUVmax in a pretreatment scan was found to be related to poorer overall survival (OS) and progression-free survival (p = 0.04 and 0.02, respectively). Furthermore, a large tumor size in a pretreatment scan was associated with poorer OS but not with progression-free survival (p < 0.01 and p = 0.07, respectively). By multivariate analyses, a high SUVmax, a large tumor size in a pretreatment scan and diffuse large B-cell lymphoma histology were significantly associated with poorer OS [p = 0.04/hazard ratio (HR) = 3.54, p < 0.01/HR = 5.52, and p = 0.02/HR = 3.38, respectively). CONCLUSION: SUVmax and tumor size determined by a pretreatment ¹8F-FDG PET/CT result as significant predictors of OS in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated by RIT.

Comparison of (18)F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma.

OBJECTIVE: We compared the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and (99 m)Tc-methylene diphosphonate bone scintigraphy (BS) for the detection of bone metastasis in osteosarcoma. MATERIALS AND METHODS: We retrospectively reviewed 206 patients with stage II-IV osteosarcoma treated with surgery and chemotherapy as well as at least one paired PET/CT and BS scan (defined as an examination). PET/CT and BS images were interpreted separately. When analyzing the diagnostic yield of a combination of PET/CT and BS (PET/CT+BS), an examination was considered positive if either PET/CT or BS scored positive. The final diagnosis was obtained from histological findings or clinical follow-up with imaging studies for at least 6 months. Diagnostic performances of PET/CT, BS, and their combinations were calculated. RESULTS: Out of 833 examinations in 206 patients, 55 with 101 lesions in 38 patients were confirmed as bone metastases. The sensitivity, specificity, and diagnostic accuracy were 95, 98, and 98%, respectively, for PET/CT; 76, 97, and 96%, respectively, for BS; and 100, 96, and 97%, respectively, for PET/CT+BS in an examination-based analysis. Lesion-based analysis demonstrated that the sensitivity of PET/CT+BS (100%) was significantly higher than that of PET/CT (92%) or BS (74%) alone. BS detected significantly less bone metastases in the growth plate region than outside the growth plate region (22 vs. 77%). CONCLUSIONS: PET/CT is more sensitive and accurate than BS for diagnosing bone metastases in osteosarcoma. The combined use of PET/CT and BS improves sensitivity.

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.

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.