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BackgroundPheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells.MethodsWe are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211At] MABG is 0.65 MBq/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123I] MIBG scintigraphy on reducing tumor accumulation, and quality of life.Trials registrationjRCT2021220012 registered on 17 June 2022.

Abstract With the growing need to obtain ideal materials for various applications, there is an increasing interest in computational methods to rapidly and accurately search for materials. Molecular dynamics simulation is one of the successful methods used to investigate liquid electrolytes with high transport properties applied in lithium-ion batteries. However, further reduction in computational cost is required to find a novel material with the desired properties from a large number of combinations. In this study, we demonstrate an effective fast evaluation technique for shear viscosity and ionic conductivity by molecular dynamics simulation for an exhaustive search of electrolyte materials with high transport properties. The proposed model was combined with a short-time correlation function of the stress tensor and empirical relationships to address the issues of inefficient and uncertain evaluation by conventional molecular dynamics methods. Because we focus on liquid electrolytes consisting of organic solvents and lithium salts, our model requires dissociation ratio and effective diffusion size of lithium salts. Our method is applied to search for the compositional combinations of electrolytes with superior transport properties even at low temperatures. These results correlate well with experimental results.

Abstract Background Halo artifacts from urinary catheters can occur due to inaccurate scatter correction, and the artifacts affect the tumor visibility in 18F-FDG PET/CT images. We investigated the incidence rate and the mechanisms of halo-artifact generation and explored several scatter correction techniques to prevent artifacts. Methods We conducted patient and phantom studies. (1) We retrospectively reviewed the cases of patients who had undergone 18F-FDG PET/CT scans. To determine the frequency of halo-artifact generation, we used the patients’ PET images with a standard scatter correction based on a tail-fitted single-scatter simulation (TF-SSS) using 4-mm voxel μ-maps (TFS 4-mm). (2) We performed phantom studies to evaluate the effects of a urine catheter and two scatter correction techniques, i.e., TF-SSS with 2-mm voxel μ-maps (TFS 2-mm) and a Monte Carlo-based single-scatter simulation (MC-SSS) using 4-mm voxel μ-maps (MCS 4-mm). The average standardized uptake values (SUVs) were measured for axial PET images. (3) Using the patients’ data, we investigated whether TFS 2-mm and MCS 4-mm can eliminate the artifacts in the clinical images. Results (1) There were 61 patients with urinary catheters; in five (8.2%), halo artifacts were observed in the TFS 4-mm PET images. (2) The phantom study clearly reproduced the halo artifacts in the TFS 4-mm PET images. The halo artifacts were generated when urine moved in the interval between the CT and PET imaging, and when the urinary catheter was placed in a circular shape. The SUVs for the TFS 4-mm and TFS-2mm PET images were underestimated at the halo-artifact regions, whereas the SUVs for the MCS 4-mm PET images were close to the true values. (3) The halo artifacts disappeared in the TFS 2-mm PET images in 4/5 patients but not 1/5 patient, whereas the halo artifacts were completely absent in the MCS 4-mm PET images in 5/5 patients. Conclusions These data suggest that halo artifacts are caused if the PET images do not correspond to the physical material in the μ-maps, which induces the scatter correction error. With the MC-SSS, it was possible to accurately estimate the scatter without generating halo artifacts.

Introduction: Apathy is a common neuropsychiatric symptom in patients with Alzheimer’s disease (AD). The striatal binding potential (BP) of 123I-FP-CIT (N-δ-fluoropropyl-2β-carbomethoxy-3β-[4-iodophenyl]tropane) single-photon emission computed tomography (SPECT) is correlated with the degree of apathy in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). This study aimed to determine if dopaminergic activity in the basal ganglia is associated with the development of apathy in AD. Methods: Nineteen subjects with AD were included and underwent 123I-FP-CIT-SPECT. Patients with other types of dementia as a comorbidity, those taking antidepressants, and those with overt parkinsonism were excluded. Apathy was assessed using the Apathy Evaluation Scale Informant-Japanese version (AES-I-J). SPECT images were overlaid with images in striatal regions of interest (ROIs), and the SPECT values in these regions were counted. The relationship between BP values and AES-I-J scores was investigated using Spearman’s rank correlation coefficient. Results: Significant inverse correlations were observed between BP values and AES-I-J scores in the left caudate nucleus and there was a marginally significant inverse correlation in the right caudate nucleus. Conclusion: The pathological basis of apathy might be the impairment of the dopaminergic nervous system. Further studies on more subjects with AD, healthy controls, and patients with PD and DLB are needed.

Abstract Background As the number of PET/CT scanners increases and FDG PET/CT becomes a common imaging modality for oncology, the demands for automated detection systems on artificial intelligence (AI) to prevent human oversight and misdiagnosis are rapidly growing. We aimed to develop a convolutional neural network (CNN)-based system that can classify whole-body FDG PET as 1) benign, 2) malignant or 3) equivocal. Methods This retrospective study investigated 3485 sequential patients with malignant or suspected malignant disease, who underwent whole-body FDG PET/CT at our institute. All the cases were classified into the 3 categories by a nuclear medicine physician. A residual network (ResNet)-based CNN architecture was built for classifying patients into the 3 categories. In addition, we performed a region-based analysis of CNN (head-and-neck, chest, abdomen, and pelvic region). Results There were 1280 (37%), 1450 (42%), and 755 (22%) patients classified as benign, malignant and equivocal, respectively. In the patient-based analysis, CNN predicted benign, malignant and equivocal images with 99.4, 99.4, and 87.5% accuracy, respectively. In region-based analysis, the prediction was correct with the probability of 97.3% (head-and-neck), 96.6% (chest), 92.8% (abdomen) and 99.6% (pelvic region), respectively. Conclusion The CNN-based system reliably classified FDG PET images into 3 categories, indicating that it could be helpful for physicians as a double-checking system to prevent oversight and misdiagnosis.

Abstract Background We investigated the prognostic predictive value of the combination of fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET in patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiation therapy (SBRT). Patients and methods We prospectively examined patients with pathologically proven NSCLC; all underwent FDG and FMISO PET/CT scans before SBRT. PET images were acquired using a whole-body time-of-flight PET-CT scanner with respiratory gating. We classified them into recurrent and non-recurrent groups based on their clinical follow-ups and compared the groups' tumor diameters and PET parameters (i.e., maximum of the standardized uptake value (SUVmax), metabolic tumor volume, tumor-to-muscle ratio, and tumor-to-blood ratio). We performed univariate analysis to evaluate the impact of the PET variables on the patients' progression-free survival (PFS). We divided the patients by thresholds of FDG SUVmax and FMISO SUVmax obtained from receiver operating characteristic analysis for assessment of recurrence rate and PFS. Results Thirty-two NSCLC patients (19 male and 13 females; median age, 83 years) were enrolled. All received SBRT. At the study endpoint, 23 patients (71.9%) were non-recurrent and nine patients (28.1%) had recurrent disease. Significant between-group differences were observed in tumor diameter and all the PET parameters, demonstrating that those were significant predictors of the recurrence in all patients. In the 22 patients with tumors > 2 cm, tumor diameter and FDG SUVmax were not significant predictors. Thirty-two patients were divided into three patterns from the thresholds of FDG SUVmax (6.81) and FMISO SUVmax (1.89); A, low FDG and low FMISO (n = 14); B, high FDG and low FMISO (n = 8); C, high FDG and high FMISO (n = 10). No pattern A patient experienced tumor recurrence, whereas two pattern B patients (25%) and seven pattern C patients (70%) exhibited recurrence. A Kaplan-Meier analysis of all patients revealed a significant difference in PFS between patterns A and B (p = 0.013) and between patterns A and C (p < 0.001). In the tumors > 2 cm patients, significant differences in PFS were demonstrated between pattern A and C patients (p = 0.002). Conclusion The combination of FDG- and FMISO-PET can identify patients with a baseline risk of recurrence and indicate whether additional therapy might be performed to improve survival.

Summary: Medication-related osteonecrosis of jaws (MRONJ) is one of the most complicated inflammatory conditions in oral and maxillofacial region. It is very difficult to correctly evaluate the degree and extent of necrosis and infection. This refractory osteonecrosis often needs extended surgery, leading to impaired quality-of-life. We have performed hyperbaric oxygen therapy (HBO) combined with conservative surgery for advanced cases. We have appraised the value of FDG-PET and 3-phase bone scintigraphy in the diagnosis and management of this condition. MRONJ showed significantly higher SUVmax on FDG-PET than the others. Although the 3 phase pool bone images did not change significantly, perfusion and static bone image as well as PET showed remarkable response to HBO for MRONJ. SUVmax after HBO was significantly lower than those of before HBO. These preliminary results indicate that FDG-PET is useful for monitoring the effect of HBO for MRONJ.

Abstract Background To facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[18F]-fluoropropyl)-2-nitroimidazole ([18F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [18F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [18F]fluoromisonidazole ([18F]FMISO). Results The single administration of [18F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [18F]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [18F]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.4 ± 0.7 μSv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 ± 13.6 μSv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 ± 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [18F]FMISO and [18F]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers’ diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [18F]DiFA PET at 1 h and 2 h were not significantly different from those obtained with [18F]FMISO PET at 4 h ([18F]DiFA at 1 h, p = 0.32; [18F]DiFA at 2 h, p = 0.08). Moreover, [18F]DiFA PET at both 1 h (k = 0.68) and 2 h (k = 1.00) showed better inter-observer reproducibility than [18F]FMISO PET at 4 h (k = 0.59). Conclusion [18F]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [18F]DiFA is very rapidly cleared via the urinary system. [18F]DiFA PET generated comparable images to [18F]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [18F]DiFA PET for hypoxia imaging and for a multicenter trial.

Abstract Background Eribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature. 18F-Fluoromisonidazole (18F-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized 18F-FMISO to clarify the effects of eribulin on the tumor hypoxic condition in comparison with histological findings. Material and methods Mice bearing a human cancer cell xenograft were intraperitoneally administered a single dose of eribulin (0.3 or 1.0 mg/kg) or saline. Three days after the treatment, mice were injected with 18F-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral 18F-FMISO accumulation levels and histological characteristics were determined. PET/CT was performed pre- and post-treatment with eribulin (0.3 mg/kg, i.p.). Results The 18F-FMISO accumulation levels and percent pimonidazole-positive hypoxic area were significantly lower, whereas the number of microvessels was higher in the tumors treated with eribulin. The PET/CT confirmed that 18F-FMISO distribution in the tumor was decreased after the eribulin treatment. Conclusions Using 18F-FMISO, we demonstrated the elimination of the tumor hypoxic condition by eribulin treatment, concomitantly with the increase in microvessel density. These findings indicate that PET imaging using 18F-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.

Understanding the fundamental chemistry in Li-O2 battery holds importance to the development of superior energy devices. Here the authors report that the oxygen reduction reaction in Li-O2 battery exhibits negative differential resistance, which can work as an indicator to the reaction pathway.

Abstract Introduction This systematic review aims to elucidate the diagnostic accuracy of radiological examinations to distinguish between brain radiation necrosis (BRN) and tumor progression (TP). Methods We divided diagnostic approaches into two categories as follows—conventional radiological imaging [computed tomography (CT) and magnetic resonance imaging (MRI): review question (RQ) 1] and nuclear medicine studies [single photon emission CT (SPECT) and positron emission tomography (PET): RQ2]—and queried. Our librarians conducted a comprehensive systematic search on PubMed, the Cochrane Library, and the Japan Medical Abstracts Society up to March 2015. We estimated summary statistics using the bivariate random effects model and performed subanalysis by dividing into tumor types—gliomas and metastatic brain tumors. Results Of 188 and 239 records extracted from the database, we included 20 and 26 studies in the analysis for RQ1 and RQ2, respectively. In RQ1, we used gadolinium (Gd)-enhanced MRI, diffusion-weighted image, MR spectroscopy, and perfusion CT/MRI to diagnose BRN in RQ1. In RQ2, 201Tl-, 99mTc-MIBI-, and 99mTc-GHA-SPECT, and 18F-FDG-, 11C-MET-, 18F-FET-, and 18F-BPA-PET were used. In meta-analysis, Gd-enhanced MRI exhibited the lowest sensitivity [63%; 95% confidence interval (CI): 28–89%] and diagnostic odds ratio (DOR), and combined multiple imaging studies displayed the highest sensitivity (96%; 95% CI: 83–99%) and DOR among all imaging studies. In subanalysis for gliomas, Gd-enhanced MRI and 18F-FDG-PET revealed low DOR. Conversely, we observed no difference in DOR among radiological imaging in metastatic brain tumors. However, diagnostic parameters and study subjects often differed among the same imaging studies. All studies enrolled a small number of patients, and only 10 were prospective studies without randomization. Conclusions Differentiating BRN from TP using Gd-enhanced MRI and 18F-FDG-PET is challenging for patients with glioma. Conversely, BRN could be diagnosed by any radiological imaging in metastatic brain tumors. This review suggests that combined multiparametric imaging, including lesional metabolism and blood flow, could enhance diagnostic accuracy, compared with a single imaging study. Nevertheless, a substantial risk of bias and indirectness of reviewed studies hindered drawing firm conclusion about the best imaging technique for diagnosing BRN.

Background: Diagnostic reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily diagnostic reports of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) – computed tomography (CT). If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret diagnostic reports. We aimed to clarify whether the lesion can be localized using SUVmax strings.Methods: The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax = 3.14 was given, the voxels with 3.135 ≤ SUVmax < 3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that “identical detection” was achieved when only single voxel satisfied the criterion.Results: A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax < 2), 79.5% (2 ≤ SUVmax < 5), and 97.8% (5 ≤ SUVmax) of lesions.Conclusion: In this preliminary study, SUVmax of FDG PET-CT could be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax < 2 were difficult to identify. The proposed method may have potential to make use of diagnostic reports retrospectively for constructing training datasets for AI.

Objective We aimed to evaluate the association of the prognostic impact of coronary revascularisation with physician-referred non-invasive diagnostic imaging tests (single photon emission CT (SPECT) vs coronary CT angiography) for coronary artery disease.Design A post hoc analysis of a subgroup from the patient cohort recruited for the Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study.Setting Multiple centres in Japan.Participants From the data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred non-invasive imaging tests, 1205 patients with SPECT as an initial strategy and 625 with CT as an initial strategy were analysed. We assessed the effect of revascularisation (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata.Primary and secondary outcome measures Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalisation for heart failure and late revascularisation, were followed up for 1 year. The χ2 test, Student’s t-test, Kaplan-Meier analysis, log-rank test and multivariable Cox proportional hazard model were used in data analysis.Results A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularisation. Although in each stratum, the cumulative 1 year incidence of MACEs was significantly higher in patients who underwent revascularisation than in those who did not (SPECT stratum: 9.1 vs 1.2%, log-rank p

Abstract Background Cardiac sarcoidosis (CS) is a rare but potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and, most notably, sudden cardiac death. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays important roles not only in diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A volume-based analysis of parameters measured by FDG PET, so-called cardiac metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as the volume within the boundary determined by a reference tissue such as the liver and the blood pool uptake. However, there is a possibility that oral steroid therapy could lead to variations of the liver and the blood pool uptake. Here, we attempted to evaluate the steroid effects on the liver and the blood pool uptake. A total of 38 CS patients who underwent FDG PET/CT before and during steroid therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in the right lobe of the liver and descending aorta (DA). The maximum standardized uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared between time points before and during steroid therapy. Results The SUVmax, SUVmean, and SUVpeak of the liver during steroid therapy significantly increased from the time point before the therapy (SUVmax 3.5 ± 0.4 vs. 3.8 ± 0.6, p = 0.014; SUVmean 2.7 ± 0.3 vs. 3.0 ± 0.5, p = 0.0065; SUVpeak 3.0 ± 0.4 vs. 3.4 ± 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did not significantly change (SUVmax 2.2 ± 0.3 vs. 2.2 ± 0.4, p = 0.46; SUVmean 1.9 ± 0.3 vs. 2.0 ± 0.4, p = 0.56; SUVpeak 2.0 ± 0.3 vs. 2.0 ± 0.3, p = 0.70). Conclusions We measured FDG uptake in the liver and blood pool before and during steroid therapy. Steroid therapy increased the liver uptake but not the blood pool uptake. Our findings suggested that the DA uptake is a more suitable threshold than liver uptake to evaluate therapeutic effects using volume-based analysis of cardiac FDG PET.

Abstract Background Programmed cell death 1 (PD-1) inhibitors act as immune checkpoint inhibitors and are more effective for improving survival time with less toxicity as compared with conventional chemotherapies. In anti PD-1 therapy, it is important to evaluate metabolism in the cancer microenvironment, as this helps to clarify the pathological conditions. Herein, we investigate the early effects of PD-1 therapy on 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells. Results In a B16F10 melanoma model, [18F]FDG-positron emission tomography (PET) was performed before treatment and 7 days after the start of treatment. Values were calculated as the percentage-injected activity per gram of tissue (%IA/g). Flow-cytometry was then performed to assess immune cell populations and glucose metabolism. There was a negligible difference in [18F]FDG uptake between tumors in the treatment group and non-treatment group before the treatment. In contrast, mean [18F]FDG uptake in the treatment group tumors was significantly higher (8.06 ± 0.48 %IA/g; P = 0.0074) than that in the non-treatment group (4.02 ± 1.03 %IA/g) after anti PD-1 treatment. Assessment of tumor immune cell populations showed that treatment slightly enriched CD8+ T cells and CD4+ T cells; however, infiltration of immune cells was negligible, and thus, immune cells were not responsible for the increase in [18F]FDG uptake. On the other hand, anti PD-1 treatment significantly increased glucose transporter 1 (GLUT1) and hexokinase II expression in CD45− cancer cells, indicating that anti PD-1 treatment increased glucose metabolism in cancer cells. Conclusion The present study shows that anti PD-1 therapy increases glucose metabolism in cancer cells.

Abstract Background Hypoxic cancer cells are thought to be radioresistant and could impact local recurrence after radiotherapy (RT). One of the major hypoxic imaging modalities is [18F]fluoromisonidazole positron emission tomography (FMISO-PET). High FMISO uptake before RT could indicate radioresistant sites and might be associated with future local recurrence. The predictive value of FMISO-PET for intra-tumoral recurrence regions was evaluated using high-resolution semiconductor detectors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods Nine patients with local recurrence and 12 patients without local recurrence for more than 3 years were included in this study. These patients received homogeneous and standard doses of radiation to the primary tumor irrespective of FMISO uptake. The FMISO-PET image before RT was examined via a voxel-based analysis, which focused on the relationship between the degree of FMISO uptake and recurrence region. Results In the pretreatment FMISO-PET images, the tumor-to-muscle ratio (TMR) of FMISO in the voxels of the tumor recurrence region was significantly higher than that of the non-recurrence region (p

BACKGROUND:Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is far less common than 18F-FDG (FDG) and two separate PET scans result in doubled cost and radiation exposure to the patient, we aimed to predict hypoxia from FDG PET with new techniques of voxel based analysis and texture analysis. METHODS:Thirty-eight patients with head-and-neck cancer underwent consecutive FDG and FMISO PET scans before any treatment. ROIs enclosing the primary cancer were compared in a voxel-by-voxel manner between FDG and FMISO PET. Tumour hypoxia was defined as the volume with a tumour-to-muscle ratio (TMR) > 1.25 in the FMISO PET and hypermetabolic volume was defined as >50% SUVmax in the FDG PET. The concordance rate was defined as percentage of voxels within the tumour which were both hypermetabolic and hypoxic. 38 different texture analysis (TA) parameters were computed based on the ROIs and correlated with presence of hypoxia. RESULTS:Within the hypoxic tumour regions, the FDG uptake was twice as high as in the non-hypoxic tumour regions (SUVmean 10.9 vs. 5.4; p

Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine.

Background: Positron emission tomography with 11C-methionine (MET) is well established in the diagnostic work-up of malignant brain tumors. Texture analysis is a novel technique for extracting information regarding relationships among surrounding voxels, in order to quantify their inhomogeneity. This study evaluated whether the texture analysis of MET uptake has prognostic value for patients with glioma. Methods: We retrospectively analyzed adults with glioma who had undergone preoperative metabolic imaging at a single center. Tumors were delineated using a threshold of 1.3-fold of the mean standardized uptake value for the contralateral cortex, and then processed to calculate the texture features in glioma. Results: The study included 42 patients (median age: 56 years). The World Health Organization classifications were grade II (7 patients), grade III (17 patients), and grade IV (18 patients). Sixteen (16.1%) all-cause deaths were recorded during the median follow-up of 18.8 months. The univariate analyses revealed that overall survival (OS) was associated with age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01–1.08, p = 0.0093), tumor grade (HR 3.64, 95% CI 1.63–9.63, p = 0.0010), genetic status (p < 0.0001), low gray-level run emphasis (LGRE, calculated from the gray-level run-length matrix) (HR 2.30 × 1011, 95% CI 737.11–4.23 × 1019, p = 0.0096), and correlation (calculated from the gray-level co-occurrence matrix) (HR 5.17, 95% CI 1.07–20.93, p = 0.041). The multivariate analyses revealed OS was independently associated with LGRE and correlation. The survival curves were also significantly different (both log-rank p < 0.05). Conclusion: Textural features obtained using preoperative MET positron emission tomography may compliment the semi-quantitative assessment for prognostication in glioma cases.

Therapeutic response is evaluated using the diameter of tumors and quantitative parameters of 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET). Tumor response to molecular-targeted drugs and immune checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration and morphological change after the therapy. Cancer stem cells, immunologically competent cells, and metabolism of cancer are considered targets of novel therapy. Accumulation of FDG reflects the glucose metabolism of cancer cells as well as immune cells in the tumor microenvironment, which differs among patients according to the individual immune function; however, FDG-PET could evaluate the viability of the tumor as a whole. On the other hand, specific imaging and cell tracking of cancer cell or immunological cell subsets does not elucidate tumor response in a complexed interaction in the tumor microenvironment. Considering tumor heterogeneity and individual variation in therapeutic response, a radiomics approach with quantitative features of multimodal images and deep learning algorithm with reference to pathologic and genetic data has the potential to improve response assessment for emerging cancer therapy.

Glioma is the most common malignant brain tumor. Hypoxia is closely related to the malignancy of gliomas, and positron emission tomography (PET) can noninvasively visualize the degree and the expansion of hypoxia. Currently, 18F-fluoromisonidazole (FMISO) is the most common radiotracer for hypoxia imaging. The clinical usefulness of FMISO PET has been established; it can distinguish glioblastomas from lower-grade gliomas and can predict the microenvironment of a tumor, including necrosis, vascularization, and permeability. FMISO PET provides prognostic information, including survival and treatment response information. Because hypoxia decreases a tumor’s sensitivity to radiation therapy, dose escalation to an FMISO-positive volume is an attractive strategy. Although this idea is not new, an insufficient amount of evidence has been obtained regarding this concept. New tracers for hypoxia imaging such as 18F-DiFA are being tested. In the future, hypoxia imaging will play an important role in glioma management.

The original version of this Article contained an error in the title, which was previously incorrectly given as ‘Negative differential resistance as a critical indicator for the discharge capacity of lithium-oxygene batteries’. The correct version states ‘lithium-oxygen’ in place of ‘lithium-oxygene’. This has been corrected in both the PDF and HTML versions of the Article.

Bevacizumab (BEV), a humanized monoclonal antibody, become a currently important chemotherapeutic option for the patients with recurrent glioma. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET have the potential to detect BEV-resistant gliomas in the early-stage.We reviewed the FMISO PET and MRI appearances before and 3 to 4 courses after BEV treatment on 18 recurrent glioma patients. FMISO accumulation was assessed by visual inspection and semi-quantitative values which were tumor-to-normal (T/N) ratio and hypoxic volume. MRI responses were evaluated based on RANO (Response Assessment in Neuro-Oncology) criteria. The prognostic analysis was performed in relation to the response assessment by FMISO PET and MRI using overall survival (OS) after BEV application.After BEV application, MRI revealed partial response in 14 of 18 patients (78%), of which 9 patients also demonstrated decreased FMISO accumulation. These 9 patients (50%) were classified as "MRI-FMISO double responder". As for the other 5 patients (28%), FMISO accumulation volumes increased or remained stable after BEV treatment although partial responses were achieved on MRI. Therefore, these cases were classified as "MRI-only responder". The remaining 4 patients (22%) did not show treatment response on FMISO PET or MRI ("non-responder"). MRI-FMISO double responders showed significantly longer OS than that in other groups (median 12.4 vs 5.7 months; P < 0.001), whereas there were no overall survival difference between MRI-only responders and non-responders (median OS, 5.7 and 4.8 months; P = 0.58). Among the pre-treatment clinical factors, high FMISO T/N ratio was a significant prognostic factor of overall survival in these patients under the assessment of Cox proportional hazard model.Recurrent gliomas with decreasing FMISO accumulation after short-term BEV application could derive a survival benefit from BEV treatment. Change in FMISO PET appearance can identify BEV-resistant gliomas in early-stage regardless of MRI findings in a comprehensible way.

OBJECTIVE:To determine the relationship between tumor glucose metabolism and tumor blood flow (TBF) in head and neck squamous cell carcinoma (HNSCC). METHODS:We retrospectively analyzed 57 HNSCC patients. Tumor glucose metabolism was assessed by maximum and mean standardized uptake values (SUVmax and SUVmean) obtained by 18F-fluorodeoxyglucose positron-emission tomography. TBF values were obtained by arterial spin labeling with 3-tesla MRI. The correlations between both SUVs and TBF were assessed in the total series and among patients divided by T-stage (T1-T3 and T4 groups) and tumor location (pharynx/oral cavity and sinonasal cavity groups). Pearson's correlation coefficients were calculated for significant correlations. RESULTS:Significant correlations were detected: a negative correlation in the advanced T-stage group (TBF and SUV max: r, -0.61, SUVmean: r, -0.62), a positive correlation in the non-advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, 0.70, SUVmean: r, 0.73), a negative correlation in the advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, -0.62, SUVmean: r, -0.65), and a negative correlation in the advanced T-stage sinonasal cavity group (TBF and SUVmax: r, -0.61, SUVmean: r, -0.65). CONCLUSION:Significant correlations between glucose uptake and TBF in HNSCC were revealed by the division of T-stage and tumor location.