A LANA peptide inhibits tumor growth by inducing CHD4 protein cleavage and triggers cell death.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection, and viral genes are poised to be transcribed in the latent chromatin. In the poised chromatins, KSHV latency-associated nuclear antigen (LANA) interacts with cellular chromodomain-helicase-DNA-binding protein 4 (CHD4) and inhibits viral promoter activation. CHD4 is known to regulate cell differentiation by preventing enhancers from activating promoters. Here, we identified a putative CHD4 inhibitor peptide (VGN73) from the LANA sequence corresponding to the LANA-CHD4 interaction surface. The VGN73 interacts with CHD4 at its PHD domain with a dissociation constant (KD) of 14 nM. Pre-treatment with VGN73 enhanced monocyte differentiation into macrophages and globally altered the repertoire of activated genes in U937 cells. Furthermore, the introduction of the peptide into the cancer cells induced caspase-mediated CHD4 cleavage, triggered cell death, and inhibited tumor growth in a xenograft mouse model. The VGN73 may facilitate cell differentiation therapy.

Proposing adjustments to heat safety thresholds for junior high and high school sports clubs in Japan.

With higher temperatures expected in the future due to global climate change, addressing health risks such as heat illness is increasingly important. In Japan, thousands of heat illness cases occur annually during school sports club activities. The risk may vary by sport, location, and region, but how heat safety thresholds (HSTs) should be adjusted to provide effective guidelines remains uncertain. Thus, we conducted a case-crossover study using data of heat illness cases and wet-bulb globe temperature (WBGT) throughout Japan to evaluate the heat illness risk for the current HSTs and propose adjustments. A significant relationship was found between heat illness incidence and WBGT at the time of the incident, as well as the average WBGT one and two days prior. The risk significantly varies with factors such as club, region, location, year, month, and the average WBGT in summer. Therefore, we recommend lowering the current HSTs by one category (3 °C) in the following cases: (1) clubs at high risk (baseball, softball, soccer/futsal, tennis, track and field, kyudo, and other with sustained exercise or thick uniforms); (2) from April to June; (3) in cooler regions (Hokkaido, Tohoku, Hokuriku, or where the average WBGT in summer≦18℃); (4) for outdoor activities; (5) when heat rapidly increases without adequate heat acclimatization. These findings may inform educators, students, sports authorities, and policymakers in adjusting HSTs to reduce the incidence of heat illness, thereby ensuring safer environments for school sports activities.

A novel algorithm developed using machine learning and a J-ACCESS database can estimate defect scores from myocardial perfusion single-photon emission tomography images.

BACKGROUND: Stress myocardial perfusion single-photon emission computed tomography (SPECT) imaging (MPI) has been used to diagnose and predict the prognoses of patients with coronary artery disease (CAD). An ongoing multicenter collaboration established a Japanese database (J-ACCESS) in 2001 that includes a risk model and expert interpretations. The present study aimed to develop a novel algorithm using machine learning (ML) and resources from the J-ACCESS database to aid SPECT image interpretation. METHODS: We analyzed data from 1288 patients in J-ACCESS 3 and 4 databases. Three-dimensional (3D) stereoscopic images of left ventricular myocardial perfusion were reconstructed with linear transformation from the original short-axis data. Segments were extracted from U-Net, then features were extracted from each segment during the ML process. We estimated segmental scores based on weighted features obtained from fully connected layers. Correlations between segment scores interpreted by nuclear cardiology experts and estimated by ML were evaluated using a 17-segment model, summed stress (SSS), summed rest (SRS), and summed difference (SDS) scores, and ratios (%) of summed different scores (%SDS). RESULTS: The complete concordance rate of scores assessed by the experts and estimated by ML was 79.6%. The underestimated and overestimated rates were 10.3% and 10.0%, respectively. Associations between defect scores assessed by experts and ML were close, with correlation coefficients (r) of 0.923, 0.917, 0.842 and 0.853 for SSS, SRS, SDS, %SDS, respectively (p < 0.0001 for all). CONCLUSIONS: We created a new algorithm to estimate MPI scores using ML and the J-ACCESS database. This algorithm should provide accurate MPI interpretation even in facilities without specialist nuclear cardiologists, and might facilitate therapeutic decision-making and predict prognoses.

Cardiac sympathetic activity and lethal arrhythmic events: insight into bell-shaped relationship between 123I-meta-iodobenzylguanidine activity and event rates.

BACKGROUND: 123I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts. RESULTS: We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I. CONCLUSIONS: The relationship between cardiac 123I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.

An atlas of chromatin landscape in KSHV-infected cells during de novo infection and reactivation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus with a double-stranded DNA capable of establishing latent infection in the host cell. During latency, only a limited number of viral genes are expressed in infected host cells, and that helps the virus to evade host immune cell response. During primary infection, the KSHV genome is chromatinized and maintained as an episome, which is tethered to the host chromosome via Latency Associated Nuclear Antigen (LANA). The KSHV episome undergoes the same chromatin modification with the host cell chromosome and, therefore, is regulated by various epigenetic modifications, such as DNA methylation, histone methylation, and histone acetylation. The KSHV genome is also organized in a spatiotemporal manner by forming genomic loops, which enable simultaneous and coordinated control of dynamic gene transcription, particularly during the lytic replication phase. The genome-wide approaches and advancing bioinformatic tools have increased the resolution of studies on the dynamic transcriptional control and our understanding of KSHV latency-lytic switch regulation. We will summarize our current understanding of the epigenetic gene regulation on the KSHV chromatin.

Evaluating the diagnostic efficacy of whole-body MRI versus 123I-mIBG/131I-mIBG imaging in metastatic pheochromocytoma and paraganglioma.

This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and 123I-mIBG as a pretreatment screening for 131I-mIBG therapy. Two expert reviewers evaluated WB-MRI, 123I-mIBG images, and post-therapy 131I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)-area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in 123I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy 131I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images.

Sympathetic 123I-metaiodobenzylguanidine index for Lewy body disease: probability-based diagnosis and identifying patients exempt from late imaging.

OBJECTIVE: We aimed to establish a practical diagnostic index for Lewy body diseases (LBD), such as Parkinson's disease and dementia, with Lewy bodies in outpatient settings and criteria for exempting patients from late imaging. METHODS: We acquired early and late 123I-metaiodobenzylguanidine (MIBG) images from 108 consecutive patients with suspected LBD and standardized heart-to-mediastinum (H/M) ratios for collimator conditions. Exclusions included young-onset Parkinson's disease (age < 50 years) and genetic transthyretin-type amyloidosis. We developed logistic models incorporating H/M ratios with or without age (n = 92). The sympathetic MIBG index for LBD (SMILe index), categorized LBD likelihood from 0 (lowest) to 1 (highest). Diagnostic accuracy was assessed as the area under the receiver operating characteristic (ROC) curve (AUC). The characteristics of the new index were compared with H/M ratios. The need for late imaging was explored using the SMILe index. RESULTS: Early or late SMILe indexes using a single H/M ratio variable discriminated LBD from non-LBD. The AUC values for early and late SMILe indexes were 0.880 and 0.894 (p < 0.0001 for both), identical to those for early and late H/M ratios. The sensitivity and the specificity of early SMILe indexes with a 0.5 threshold were 76% and 90%, achieving accuracy of accuracy 86%. Similarly, the late SMILe index demonstrated a sensitivity of 76% and specificity of 87%, with an accuracy of 84%. Early SMILe indexes < 0.3 or > 0.7 (representing 84% patients) indicated a diagnosis without a late MIBG study. CONCLUSION: The 123I-MIBG-derived SMILe indexes provide likelihood of LBD, and those with a 50% threshold demonstrated optimal diagnostic accuracy for LBD. The index values of either < 0.3 or > 0.7 accurately selected patients who do not need late imaging.

Absolute quantitation of sympathetic nerve activity using [123I] metaiodobenzylguanidine SPECT-CT in neurology.

BACKGROUND AND PURPOSE: The ability of [123I]metaiodobenzylguanidine (MIBG) sympathetic nerve imaging with three-dimensional (3D) quantitation to clinically diagnose neurological disorders has not been evaluated. This study compared absolute heart counts calculated as mean standardized uptake values (SUVmean) using conventional planar imaging and assessed the contribution of [123I]MIBG single-photon emission computed tomography (SPECT)-CT to the diagnosis of neurological diseases. METHODS: Seventy-two patients with neurological diseases were consecutively assessed using early and delayed [123I]MIBG SPECT-CT and planar imaging. Left ventricles were manually segmented in early and delayed SPECT-CT images, then the SUVmean and washout rates (WRs) were calculated. Heart-to-mediastinum ratios (HMRs) and WRs on planar images were conventionally computed. We investigated correlations between planar HMRs and SPECT-CT SUVmeans and between WRs obtained from planar and SPECT-CT images. The cutoff for SPECT-CT WRs defined by linear regression and that of normal planar WRs derived from a database were compared with neurological diagnoses of the patients. We assigned the patients to groups according to clinical diagnoses as controls (n = 6), multiple system atrophy (MSA, n = 7), progressive supranuclear palsy (PSP, n = 17), and Parkinson's disease or dementia with Lewy bodies (PD/DLB, n = 19), then compared SPECT-CT and planar image parameters. RESULTS: We found significant correlations between SPECT-CT SUVmean and planar HMR on early and delayed images (R2 = 0.69 and 0.82, p < 0.0001) and between SPECT-CT and planar WRs (R2 = 0.79, p < 0.0001). A threshold of 31% for SPECT-CT WR based on linear regression resulted in agreement between planar and SPECT-CT WR in 67 (93.1%) of 72 patients. Compared with controls, early and delayed SUVmean in patients with PSP and MSA tended more towards significance than planar HMR. This trend was similar for SPECT-CT WRs in patients with PSP. CONCLUSIONS: Absolute heart counts and SUVmean determined using [123I]MIBG SPECT-CT correlated with findings of conventional planar images in patients with neurological diseases. Three-dimensional quantitation with [123I]MIBG SPECT-CT imaging might differentiate patients with PSP and MSA from controls.

Validation of upper thermal thresholds for outdoor sports using thermal physiology modelling.

Thermal safety guidelines with upper thresholds aim to protect athletes' health, yet evidence-based sport-specific thresholds remain unestablished. Experimenting with athletes in severely hot conditions raises ethical concerns, so we used a thermo-physiological model to validate the thresholds of guidelines for outdoor sports. First, the reproducibility of the joint system thermoregulation model (JOS-3) of core temperature has been validated for 18 sports experiments (n = 213) and 11 general exercise experiments (n = 121) using the Bland - Altman analysis. Then, core temperatures were predicted using the JOS-3 in conditions corresponding to the upper thresholds, and if the 90th-99.7th percentile core temperature value (corresponding to 0.3%-10% of the participants) exceeded 40°C, the thresholds were judged as potentially hazardous. Finally, we proposed revisions for sports with potentially hazardous thresholds. As a result, the JOS-3 could simulate core temperature increases in most experiments (27/29) for six sports and general exercises with an accuracy of 0.5°C. The current upper thresholds for marathons, triathlons, and football are potentially hazardous. Suggested revisions, based on specified percentiles, include: Football: revise from wet bulb globe temperature (WBGT) 32°C to 29-31°C or not revise. Marathon: revise from WBGT 28°C to 24-27°C. Triathlon: revise from WBGT 32.2°C to 23-26°C. If conducting sports events under the revised upper thresholds proves difficult, taking measures for a possible high incidence of heat illness becomes crucial, such as placing additional medical resources, assisting heat acclimatization and cooling strategies for participants, and rule changes such as shorter match times and increased breaks.

Flare phenomenon visualized by 99mTc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from 99mTc-methylenediphosphonate (MDP) bone scintigraphy images. METHODS: We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2 years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4. We assessed the effects of the flare phenomenon (defined as a > 10% increase in the BSI within 3 months of starting chemotherapy, followed by > 10% improvement within the next 3 months) on survival using Kaplan-Meier curves and Cox proportional hazard analyses. RESULTS: The flare phenomenon was found in 26 (36%) of the 72 patients. Prostate-specific antigen (PSA), alkaline phosphatase (ALP), and hemoglobin (Hb) levels steadily increased, then deteriorated in patients with and without flare, respectively. Elevated BSI and PSA values at 3 months after starting therapy and the absence of abiraterone or/and enzalutamide therapy led to poor 2-year overall survival (OS) in the group without flare. In contrast, no influence was noticeable in the group with flare. The results of multivariable analyses that included only factors associated with PSA and BSI showed that increased baseline BSI (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.04-1.86; P = 0.023) and PSA (HR, 7.15; 95% CI 2.13-24.04; P = 0.0015) values could be independent risk factors for patients with mCRPC without flare. However, these factors lost significance during flare. The risk for all-cause death was significantly higher among patients with BSI > 4 without, than with flare. The results of univariable analyses indicated that flare positively impacted survival (HR, 0.24; 95% CI 0.06‒0.91; P = 0.035). Multivariable analysis did not identify any factors that could predict outcomes. CONCLUSION: Favorable prognosis, with fewer disturbances from other factors such as the use of abiraterone or/and enzalutamide, PSA changes, and BSI, was attainable in cases when the mCRPC patient demonstrated flare phenomenon. Follow-up bone scintigraphy at least every 3 months could help to determine the prognosis of patients with bone metastasis of mCRPC.

Novel indices representing heterogeneous distributions of myocardial perfusion imaging.

INTRODUCTION: Heterogeneous distribution in myocardial perfusion images (MPI) obtained by scintigraphy is often observed in cardiac diseases with normal myocardial perfusion. However, quantitative assessments of such heterogeneity have not been established. We hypothesized that the heterogeneity in MPI can be quantitatively evaluated through histogram analysis, calculating the standard deviation (SD), the 95% bandwidth (BW95%), and entropy. METHODS: We examined resting 99mTc-MIBI images in 20 healthy subjects and 29 patients with cardiac disease who had none or very-mild reduced myocardial perfusion evaluated as a low summed rest score (0 to 4, the range of the studied healthy subjects). Two nuclear medicine specialists blindly divided them into two groups: non-heterogeneity or heterogeneity group, based solely on their visual assessments of heterogeneity on splash and polar maps generated from single-photon emission computed tomography (SPECT) images. The %uptake was determined by dividing the tracer count of each pixel by the tracer count of the pixel with the highest value in the LV myocardium. SD, BW95%, and entropy from histogram patterns were analyzed from the polar map data array of each %uptake. We investigated whether heterogeneity could be assessed using SD, BW95, and entropy in two groups classified by visual assessments. Additionally, we evaluated the area under the curve (AUC) to identify heterogeneity in the receiver operating characteristic curve analysis. RESULTS: Based solely on visual assessments, 11 (22%) and 38 (78%) cases were classified into the non-heterogeneity and heterogeneity groups, respectively. The non-heterogeneity group consisted of only healthy subjects, and all patients with cardiac disease were classified into the heterogeneity group. The cases in the heterogeneity group had significantly higher values of heterogeneity indices (SD, BW95%, and entropy) in %uptake than those in the non-heterogeneity group (p < 0.05 for all). The AUCs of the heterogeneity indices were sufficiently high (AUCs > 0.90 for all) in distinguishing cases with visually heterogeneous distribution or patients with cardiac disease. CONCLUSIONS: Heterogeneity in MPI can be evaluated using SD, BW95%, and entropy through histogram analysis. These novel indices may help identify patients with subtle myocardial changes, even in images that show preserved perfusion (345/350).

Protocol of a Prospective Observational Study on Lifestyle and Quality of Life in Adults with Type 1 Diabetes in Japan.

INTRODUCTION: Recent studies have shown that the quality of life (QOL) of people living with type 1 diabetes (T1D) is poor and must be improved. However, the living situation and QOL of adults living with T1D in Japan have not been fully clarified. This study will examine their lifestyle, QOL, and clinical situation, as well as the relationships between them. METHODS: This is a prospective, 5-year follow-up observational study. Between December 2019 and September 2021, we enrolled adults in Japan who were living with T1D and receiving insulin therapy, and are acquiring longitudinal clinical data and the responses to seven questionnaires regarding lifestyle and QOL. The primary study outcomes are (1) the relationship between Problem Areas in Diabetes (PAID) scores and various factors including demographic data, clinical characteristics, medical history, lifestyle habits, treatment history, biochemical data, and the scores of questionnaires; and (2) the relationship between Beck Depression Inventory (BDI)-II scores and various factors aforementioned. The secondary outcomes are the relationships between various factors aforementioned and each of the following: (1) blood glucose control, (2) blood lipid control, (3) dietary patterns, (4) fear of hypoglycemia, (5) sleep patterns, and (6) physical activity. PLANNED OUTCOME: We registered 352 participants. The median age was 49 (41-63) years, and the median duration of T1D was 13 (8-20) years. All the results will be available in 2026. We expect to clarify the factors associated with decreased QOL, and that this knowledge will contribute to improving QOL in adults in Japan who are living with T1D and receiving insulin therapy. TRIAL REGISTRATION: Clinical Trials.gov identifier, UMIN000044088.

Kaposi's sarcoma-associated herpesvirus (KSHV) LANA prevents KSHV episomes from degradation.

Protein knockdown with an inducible degradation system is a powerful tool for studying proteins of interest in living cells. Here, we adopted the auxin-inducible degron (AID) approach to detail Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) function in latency maintenance and inducible viral lytic gene expression. We fused the mini-auxin-inducible degron (mAID) tag at the LANA N-terminus with KSHV bacterial artificial chromosome 16 recombination, and iSLK cells were stably infected with the recombinant KSHV encoding mAID-LANA. Incubation with 5-phenyl-indole-3-acetic acid, a derivative of natural auxin, rapidly degraded LANA within 1.5 h. In contrast to our hypothesis, depletion of LANA alone did not trigger lytic reactivation but rather decreased inducible lytic gene expression when we stimulated reactivation with a combination of ORF50 protein expression and sodium butyrate. Decreased overall lytic gene induction seemed to be associated with a rapid loss of KSHV genomes in the absence of LANA. The rapid loss of viral genomic DNA was blocked by a lysosomal inhibitor, chloroquine. Furthermore, siRNA-mediated knockdown of cellular innate immune proteins, cyclic AMP-GMP synthase (cGAS) and simulator of interferon genes (STING), and other autophagy-related genes rescued the degradation of viral genomic DNA upon LANA depletion. Reduction of the viral genome was not observed in 293FT cells that lack the expression of cGAS. These results suggest that LANA actively prevents viral genomic DNA from sensing by cGAS-STING signaling axis, adding novel insights into the role of LANA in latent genome maintenance.IMPORTANCESensing of pathogens' components is a fundamental cellular immune response. Pathogens have therefore evolved strategies to evade such cellular immune responses. KSHV LANA is a multifunctional protein and plays an essential role in maintaining the latent infection by tethering viral genomic DNA to the host chromosome. We adopted the inducible protein knockdown approach and found that depletion of LANA induced rapid degradation of viral genomic DNA, which is mediated by innate immune DNA sensors and autophagy pathway. These observations suggest that LANA may play a role in hiding KSHV episome from innate immune DNA sensors. Our study thus provides new insights into the role of LANA in latency maintenance.

Practice recommendation for measuring washout rates in 123I-BMIPP fatty acid images.

The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting 123I-ß-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of 123I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

Study Protocol for the Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitor on Organ-Specific Sympathetic Nerve Activity and Insulin Sensitivity in Participants with Type 2 Diabetes.

INTRODUCTION: Hyperinsulinemia and hyperglycemia are associated with exaggerated systemic sympathetic nerve activity (SNA) in patients with type 2 diabetes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower insulin levels, whereas sulfonylureas increase insulin levels. We will test whether these two classes of antidiabetic agents have different effects on SNA. METHODS: The present study is an ongoing, 24-week, one-center (only Kanazawa University Hospital), open-label, randomized, parallel trial (jRCTs 041200035). Participants with type 2 diabetes with multiple atherosclerosis risk factors are randomly assigned in a 1:1 manner to receive 2.5 mg luseogliflozin or 0.5 mg glimepiride once daily. The sample size was calculated to be 14 in each group, with a significance level of 0.05 and a power of 0.80. The design required 40 evaluable study participants. Our primary endpoint will be the change in muscle SNA (MSNA). The secondary endpoints included organ-specific insulin sensitivity measured by a hyperinsulinemic-euglycemic clamp study using an artificial pancreas combined with a stable isotope-labeled glucose infusion, bioelectrical impedance analysis, and organ-specific (cardiac, renal, and hepatic) 123I-meta-iodobenzylguanidine (MIBG) innervation imaging. PLANNED OUTCOMES: Study recruitment started in April 2020 and will end in June 2024, with 40 participants randomized into the two groups. The treatment follow-up of the participants is currently ongoing and is due to finish by March 2025. TRIAL REGISTRATION: The study protocol has been approved by the Certified Review Board, Kanazawa University, Ishikawa, Japan, in accordance with the guidelines stipulated in the Declaration of Helsinki (CRB4180005, 2019-001). This trial is registered with the Japan Registry of Clinical Trials, jRCTs 041200035.

Detectability of cold tumors by xSPECT bone technology compared with hot tumors: a supine phantom study.

Detecting cold as well as hot tumors is vital for interpreting bone tumors on single-photon emission computed tomography (SPECT) images. This study aimed to visually and quantitatively demonstrate the detectability of cold tumors using xSPECT technology compared with that of hot tumors in the phantom study. Five tumors of different sizes and normal bone contained a mixture of 99mTc and K2HPO4 in a spine phantom. We acquired SPECT data using an xSPECT protocol and transverse images were reconstructed using xSPECT Bone (xB) and xSPECT Quant (xQ). Mean standardized uptake values (SUVmean) in volumes of interest (VOI) were calculated. Recovery coefficients (RCs) for each tumor site were calculated with reference to radioactive concentrations. The SUVmeans of the whole vertebral body for hot tumor bone image in cortical bone phantom reconstructed by with xB and xQ were 5.77 and 4.86 respectively. The SUVmean of xB was similar to the true value. The SUVmeans for xB and xQ reconstructed images of cold tumors were both approximately 0.16. The RC of the cold tumor on xQ images increased as the tumor diameter decreased, whereas that of xB remained almost constant regardless of the tumor diameter. In conclusion, the quantitative accuracy of detecting hot and cold tumors was higher in the xB image than in the xQ image. Moreover, the visual detectability of cold tumors was also excellent in xB images.

Comparison of Taiwanese and European Calibration Factors for Heart-to-Mediastinum Ratio in Multicenter 123I-mIBG Phantom Studies.

Background: Cross-calibration of 123I-labeled meta-iodobenzylguanidine (mIBG) myocardial-derived indices is essential to extrapolate findings from several clinical centers. Here, we conducted a phantom study to generate conversion coefficients for the calibration of heart-to-mediastinum ratios and compare them between Taiwan and Europe. Methods: We used an acrylic phantom dedicated to 123I-mIBG planar imaging to calculate the conversion coefficients of 136 phantom images derived from 36 Taiwanese institutions. A European phantom image database including 191 images from 27 institutions was used. Conversion coefficients were categorized into five collimator types: low-energy (LE) high-resolution (LEHR), LE general-purpose (LEGP), extended LEGP (ELEGP), medium-energy (ME) GP (MEGP), and ME low-penetration (MELP) collimators. Results: The conversion coefficients were 0.53 ± 0.039, 0.59 ± 0.032, 0.79 ± 0.032, 0.96 ± 0.038, and 0.99 ± 0.050 for LEHR, LEGP, ELEGP, MEGP, and MELP collimators, respectively. The Taiwanese and European conversion coefficients for the LEHR, LEGP, and MELP collimators did not significantly differ. The coefficient of variation was slightly higher for the Taiwanese than the European conversion coefficients (3.7%-7.5% vs. 2.3%-5.6%). Conclusions: We calculated conversion coefficients for various types of collimators used in Taiwan using a 123I-mIBG phantom. In general, the Taiwanese and European conversion coefficients were comparable. These findings further corroborated and highlighted the need for 123I-mIBG standardization using the phantom-determined conversion coefficients.