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National Institutes for Quantum Science and Technology (QST), formerly known as the National Institute of Radiological Sciences (NIRS), has been engaged in work on radiopharmaceutical science using cyclotrons since 1974. Eight pioneering researchers founded the basis of this field of research at NIRS, and to the present, many researchers and technicians have accumulated both scientific and technical achievements, as well as inherited the spirit of research. Besides, in recent years, we have developed production systems with AVF-930 cyclotron for various 'non-standard' radioisotopes applied in both diagnosis and therapy. Here, we review the past 50 years of our activities on radioisotope and radiopharmaceutical development, as well as more recent activities. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the use of 15-(4-123I-iodophenyl)-3(R,S)-methylpentadecanoic acid (123I-BMIPP) to visualize fatty acid metabolism in bacteria for bacterial infection imaging. We found that 123I-BMIPP, which is used for fatty acid metabolism scintigraphy in Japan, accumulated markedly in Escherichia coli EC-14 similar to 18F-FDG, which has previously been studied for bacterial imaging. To elucidate the underlying mechanism, we evaluated changes in 123I-BMIPP accumulation under low-temperature conditions and in the presence of a CD36 inhibitor. The uptake of 123I-BMIPP by EC-14 was mediated via the CD36-like fatty-acid-transporting membrane protein and accumulated by fatty acid metabolism. In model mice infected with EC-14, the biological distribution and whole-body imaging were assessed using 123I-BMIPP and 18F-FDG. The 123I-BMIPP biodistribution study showed that, 8 h after infection, the ratio of 123I-BMIPP accumulated in infected muscle to that in control muscle was 1.31 at 60 min after 123I-BMIPP injection. In whole-body imaging 1.5 h after 123I-BMIPP administration and 9.5 h after infection, infected muscle exhibited a 1.33-times higher contrast than non-infected muscle. Thus, 123I-BMIPP shows potential for visualizing fatty acid metabolism of bacteria for imaging bacterial infections. [ABSTRACT FROM AUTHOR]

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. The subcommittee sent questionnaires, including the number and category of examinations as well as the kind of the radiopharmaceuticals during the 30 days of June 2022 to all nuclear medicine institutes in Japan. The total numbers of them for the year 2022 were estimated depends on the 1-month data. A total of 1095 institutes responded to the survey, including 364 positron emission tomography (PET) centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1299 in total, with 2.5% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 83.8% and 35.5%, respectively. The number of single-photon tracer studies in 2022 was 1.11 million which means increase in 2.7% in 5 years. Bone scintigraphy was a leading examination (31.0%), followed by myocardial scintigraphy (27.1%) and cerebral perfusion study (23.8%) in order. The percentage of SPECT studies showed an increase from 63.5% in previous survey to 66.8% in this survey. PET centers have also increased from 389 to 412, as compared with the previous one. One hundred and twenty-two PET centers have installed one or two in-house cyclotrons. Increasing trends of the PET studies were observed from 1992 to 2017, the trend changed and PET studies showed 1.5% decrease in 5 years. 18 F-FDG accounted for 98.6% (610,497 examinations). PET examinations using 11 C-methionine, 13 N-NH 3 and 11 C-PIB have decreased, with 1624, 2146 and 525 examinations, respectively in 2022. The total number of nuclear medicine examination was eventually increased by 1.0%. Therapies for pheochromocytoma or paraganglioma (PPGL) with 131 I-MIBG and for neuroendocrine tumor with 177 Lu-DOTA-TATE were newly started, however, a total number of targeted radionuclide therapy was decreased by 17.7% because 131 I-radioiodine and 223 Ra targeted therapies were decreased and supply of some radioisotopes was discontinued. 131 I-radioiodine targeted therapy showed a decrease in 5 years (- 15.9%), including 4099 patients for thyroid cancer. The number of out-patient thyroid bed ablation therapy with 1110 MBq of 131 I was also decreased to 1015 per year. The number of admission rooms specialized for radionuclide targeted therapy increased from 157 to 160. The number of 223 Ra targeted therapies for castration-resistant metastatic prostate cancer (mCRPC) was 1041 patients. This survey was performed during COVID-19 pandemic, however, total number of nuclear medicine examinations was almost same as previous survey (+ 1.0%). Radionuclide therapies with 131 I-MIBG and 177 Lu-DOTA-TATE were newly started, and new radionuclide therapy will be available in future, therefore, the development of radionuclide therapy will be continued. We are convinced that this survey report is useful in understanding the current status of the nuclear medicine practice in Japan, and in devising the new strategy to strengthen a role of nuclear medicine., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2022 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. Replies were obtained from 1,004 institutions out of 1,181 to which the questionnaire had been sent. A total of 911,977 radiopharmaceutical administrations were reported. Seventeen cases of adverse reactions were reported. The incidence of adverse reactions per 100,000 cases was 1.9 . No case of defective products was reported.

Here we present the guideline for the treatment of neuroendocrine tumors using Lu-177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline was prepared by a study supported by Ministry of Health, Labour, and Welfare, and approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown in this guideline are considered internationally useful as well. Only the original Japanese version is the formal document. [ABSTRACT FROM AUTHOR]

Objective(s): To appropriately use one-day myocardial perfusion imaging (MPI) with 99mTc radiopharmaceuticals (i.e. to avoid shine-through artifacts), injection doses need to be optimized and dose ratios between the 1st and 2nd scans should be maintained at = 3. However, the current state of practice in Japan is unclear. Thus, the aim of this study was to clarify the details of MPI protocols using 99mTc radiopharmaceuticals in Japan. Methods: A nationwide survey was conducted in June and July 2016. Questionnaires about stress MPI protocols using 99mTc radiopharmaceuticals were sent to 641 nuclear medicine facilities. Results: Responses were received from 246 facilities. One-day protocols were used in 97.1% of the facilities. The most common injection dose ratio was 2.5. Only 18.2% of facilities achieved the recommended injection dose ratio. Stress-only protocols were performed in only 1.7% of facilities; the primary reasons for not performing stress-only protocols were as follows: 1) "The reading-physician cannot interpret the image just after the first scan," and 2) "Preparation of radiopharmaceuticals and scan arrangements turn out to be complicated". Conclusion: Approximately 80% of nuclear medicine facilities do not follow the recommended injection dose ratio. Stress-only protocols are ideal, but are performed at very few facilities. Both optimization and standardization of stress MPI protocols using 99mTc radiopharmaceuticals are needed in Japan. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) with fluorodeoxyglucose F18 (18F-FDG) is useful for detecting malignancies, but benign lesions occasionally have false-positive 18F-FDG uptake. Here, we report the cases of five postmenopausal women with solid ovarian tumors suspected to be ovarian cancer on magnetic resonance imaging and 18F-FDG uptake. Mean age of the five patients was 57 years (range, 53-65 years). Average early standardized uptake value (SUV) of 18F-FDG was 5.76 (range, 2.2-12.0) and delayed SUV was 6.56 (range, 2.4-13.8). In all five patients, frozen section diagnosis at surgery was thecoma, and bilateral salpingo-oophorectomy was performed. On immunohistochemistry, immunoreactive glucose transporter 5 (GLUT5) expression was detected in thecoma tissues. This case shows that thecoma sometimes has positive 18F-FDG uptake on positron emission tomography-computed tomography (PET-CT), indicating the need for caution regarding false-positive PET-CT in patients with benign solid ovarian tumor. [ABSTRACT FROM AUTHOR]

There were many interesting presentations of unique studies at the Annual Meeting of the Japanese Society of Nuclear Medicine, although there were fewer attendees from Europe than expected. These presentations included research on diseases that are more frequent in Japan and Asia than in Europe, synthesis of original radiopharmaceuticals, and development of imaging devices and methods with novel ideas especially by Japanese manufacturers. In this review, we introduce recent nuclear medicine research conducted in Japan in the five categories of Oncology, Neurology, Cardiology, Radiopharmaceuticals and Technology. It is our hope that this article will encourage the participation of researchers from all over the world, in particular from Europe, in scientific meetings on nuclear medicine held in Japan. [ABSTRACT FROM AUTHOR]

Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage. [ABSTRACT FROM AUTHOR]

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2021 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. Replies were obtained from 970 institutions out of 1,194 to which the questionnaire had been sent. A total of 928,921 radiopharmaceutical administrations were reported. Twelve cases of adverse reactions were reported. The incidence of adverse reactions per 100,000 cases was 1.3. Three cases of defective products were reported. The incidence of defective products per 100,000 cases was 0.3.

Objective: Technetium etarfolatide ((99m)Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors. Administering folic acid prior to the administration of (99m)Tc-EF has been shown to improve SPECT images. Here, we conducted a phase I clinical trial to assess the safety, pharmacokinetics, and radiation dosimetry of (99m)Tc-EF injection following pre-administration of folic acid in healthy Japanese male adults.Methods: Six healthy Japanese male adults were enrolled in the study. Folic acid was intravenously administered, followed 1-3 min later by an intravenous injection of (99m)Tc-EF (740 MBq ± 20 %). Assessments of subjective symptoms and objective findings, electrocardiograms, physical examination, and laboratory tests were performed before and up to 7 days after the injection to assess the safety of (99m)Tc-EF. Blood and urine collections and whole-body planar imaging were conducted at various time points up to 24 h after the injection to assess the pharmacokinetics of (99m)Tc-EF. The internal radiation dosimetry was calculated based on the pharmacokinetics results using the MIRD method.Results: Five adverse events were observed in three subjects (50 %) after administration of the folic acid and (99m)Tc-EF, while these events were mild and non-serious. Of those five events, three were considered to be related to the administered agents. The radioactivity in blood rapidly decreased and showed a biphasic profile. The activity of (99m)Tc-EF at 5 min post injection was largest in the bone marrow, followed by the liver and kidneys, and had decreased within 24 h in all organs/tissues without appreciable retention. The pharmacokinetics results suggested that (99m)Tc-EF was mainly eliminated by kidney. The results also suggested that when administered at 925 MBq of (99m)Tc-EF, which is the maximum dose generally used for clinical trials in other countries, the corresponding effective dose of (99m)Tc-EF is equal to or less than those determined for the current radioactive diagnostic imaging agents.Conclusions: The results of this study assessing the safety and radiation dosimetry of (99m)Tc-EF with folic acid pre-administration suggested that folic acid and (99m)Tc-EF should be appropriate for further studies. No pharmacokinetics concerns were noted. [ABSTRACT FROM AUTHOR]

Conclusion: The usefulness of addition of positron emission tomography/computed tomography (PET/CT) in decisions as to whether to perform neck dissection in patients with T1-T2 lingual squamous cell carcinoma (SCC) might be limited, but adding the condition of lymph nodes with a maximum standardized uptake value (SUVmax) >4.5 to existing criteria would be helpful. Objectives: The purpose of this study was to investigate the usefulness of PET/CT for performing neck dissection in patients with T1-T2 lingual SCC. Methods: This retrospective review surveyed 19 patients with T1-T2 lingual SCC who underwent neck dissection after meeting one or more of the following criteria: (1) clinically positive nodes; (2) >4 mm thickness; (3) ≥ 3 cm longest diameter of the primary tumor. Focal 18F-fluorodeoxyglucose (FDG) uptake was considered to indicate PET-positive nodes (PET + Ns). The relation between pathologically positive nodes (p + Ns) and PET + Ns was estimated. Results: There were 14 PET + Ns at 12 of 66 levels (18%) in 8 of the 19 (42%) patients. There were also 6 p + Ns (1%) among 412 nodes at 5 cervical lymph node levels (8%) in 5 patients (26%). The sensitivity and specificity for PET/CT were 80% and 64%, respectively. The SUVmax was measured, and receiver operating characteristic (ROC) analysis was undertaken to obtain better accuracy. The sensitivity and specificity were 60% and 100% when the SUVmax cut-off value was set at 4.5. [ABSTRACT FROM AUTHOR]

The article reports on a study which identifies the differences in the approval status and regulatory actions for radiopharmaceuticals in the U.S. and Japan. The researchers have examined the similarities and differencies of the two regulatory systems since 1995. It suggests that international harmonization of the regulatory systems for manufactured novel drugs is important in the development of such drugs in other multinational countries.

Objective. Relapsing polychondritis (RPC) is relatively rare and early diagnosis is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for the diagnosis of RPC and evaluation of disease activity.Methods. Five RPC patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from a total of 13 patients were analysed.Results. Typical FDG accumulation was noted in the tracheobronchial trees of nine patients, the costal cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses of three, auricles of three, lymph nodes of three and the aorta of one. One patient showed nasal chondritis on a PET scan despite the absence of nasal changes on physical examination. Of five patients with costochondritis, four remained asymptomatic. Of nine patients with airway FDG accumulation, eight developed respiratory symptoms and all had CT abnormalities. In the other patient, airway FDG accumulation was evident despite the absence of airway symptoms and a lack of abnormalities in the respiratory function test and CT. PET also revealed bronchial chondritis in asymptomatic patients. The mean maximum standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d. 2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement.Conclusion. FDG-PET/CT is a potentially powerful tool for the early diagnosis of RPC, especially in patients without easily biopsied organ involvement. This modality also facilitates evaluation of disease extent and disease activity during treatment. [ABSTRACT FROM PUBLISHER]

Objective. This study aimed to determine whether [18F]fluorodeoxyglucose-PET/CT ([18F]FDG-PET/CT) discriminates PM/DM from non-muscular diseases and also whether FDG uptake in proximal muscles reflects the activity and severity of muscular inflammation in PM/DM.Methods. Twenty treatment-naïve PM/DM patients who underwent [18F]FDG-PET/CT were retrospectively identified by reviewing medical records. The same number of age- and sex-matched control patients with non-muscular diseases were also identified. Standardized uptake value (SUV) was calculated for each of the seven proximal muscles. For patient-based assessment, mean proximal muscle SUV was calculated by averaging the SUVs for these proximal muscles bilaterally.Results. Mean proximal muscle SUVs were significantly greater in PM/DM patients than in control patients (median 1.05 vs 0.69, P < 0.001). Mean proximal muscle SUVs significantly correlated with mean proximal manual muscle test scores (ρ = 0.49, P = 0.028) and serum levels of creatine kinase (ρ = 0.54, P = 0.015) and aldolase (ρ = 0.64, P = 0.002). Furthermore, SUVs in proximal muscles from which biopsy specimens were obtained significantly correlated with histological grade for inflammatory cell infiltration (ρ = 0.66, P = 0.002).Conclusion. Our results suggest that [18F]FDG-PET/CT is useful in the diagnosis of PM/DM when inflammation in proximal muscles is globally assessed with quantitative measurements. Our results also indicate that local FDG uptake in a proximal muscle reflects the activity of inflammation in the same muscle and provides useful information in determining the region for muscle biopsy. [ABSTRACT FROM PUBLISHER]

Conclusion: Maximum standardized uptake values (SUVmax) have prognostic value for induction chemotherapy (ICT) response and survival in oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC) patients. Pretreatment positron emission tomography with the use of fluorodeoxyglucose (18F-FDG PET) may be an aid in deciding the treatment strategy in OHSCC patients. Objectives: We investigated the association between pretreatment 18F-FDG PET and response to ICT and survival in OHSCC patients. Methods: We conducted a retrospective cohort study of 58 OHSCC patients treated at Aichi Cancer Center Hospital. The predictive impact of SUVmax of the primary tumor site was evaluated using statistical multivariate proportional hazard models. Results: Thirty-one cases (53%) were located in the oropharynx and 27 (47%) in the hypopharynx. Median SUVmax was 11.6 (range 3.2-23.5), and was significantly higher in the 8 patients with less than stable disease than in the 50 with more than partial response (median SUVmax, 17.3 vs 11.1; p = 0.002). In multivariate analysis, hazard ratios for the medium and high SUVmax groups relative to the low group were 3.07 (95% confidence interval, 0.62-15.29; p = 0.170) and 4.71 (0.97-22.89; p = 0.055), respectively, and the dose-response relationship was statistically significant (ptrend = 0.047). A similar tendency was observed on subclassification by oropharynx and hypopharynx. [ABSTRACT FROM AUTHOR]

Background In the population with cardiac sarcoidosis (CS), approximately one third lacks extracardiac involvement and is considered to have isolated CS. Recently, the Japanese Circulation Society updated the diagnostic criteria for CS, providing a methodology for diagnosing isolated CS. We aimed to assess the characteristics of isolated CS diagnosed using a multimodal imaging approach according to the updated Japanese Circulation Society guidelines. Methods and Results We retrospectively identified 161 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography for suspected CS between 2012 and 2019. According to the guidelines, patients were classified as having CS with extracardiac involvement, isolated CS, or no CS. We compared the characteristics of multimodality imaging and the prevalence of major adverse cardiovascular events. The Japanese Circulation Society criteria classified 28 patients (17%) as having CS with 4 (2%) with histological confirmation, 21 (13%) as isolated CS, and 112 (70%) as no CS. Compared with CS, isolated CS showed higher left ventricular volume and reduced left ventricular ejection fraction ( P <0.01 for all). During the median follow-up period of 522 days, 24 patients had major adverse cardiovascular events. Isolated CS (hazard ratio, 3.35; [95% CI, 1.08-10.39], P =0.036) was independently associated with major adverse cardiovascular events after adjusting for reduced left ventricular ejection fraction and steroid. In the subgroup of 41 patients with serial 18F-fluorodeoxyglucose positron emission tomography evaluation, only updated CS criteria were associated with improvement in myocardial inflammation on 18F-fluorodeoxyglucose positron emission tomography. Conclusions Isolated CS detected using the updated Japanese Circulation Society guidelines was associated with poor event-free survival and should be managed with caution.

Objectives. To evaluate whether there is a correlation between the differences in joint uptake of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) and the improvement of clinical findings in RA patients undergoing anti-TNF therapies.Methods. Twenty-two patients who received anti-TNF therapies, including infliximab for 16 patients and etanercept for 6 patients, were assessed. PET with 18F-FDG studies and clinical assessments were performed at baseline and 6 months after the initiation of therapy. The maximal standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in the bilateral shoulder, elbow, wrist, hip, knee and ankle joints. Spearman's rank correlation test was applied to assess the correlation between the SUV and the clinical parameters.Results. The ΔSUV (12 joints), the difference in the SUVmax of the affected 12 joints before and after treatment, was positively correlated with the ΔDAS28 (r = 0.609, P = 0.003), ΔDAS28-CRP (r = 0.656, P = 0.001) and Δtender joint count (TJC) (r = 0.609, P = 0.003). There were also significantly positive correlations between ΔSUV (8 joints); the difference in the SUVmax of the bilateral shoulder, elbow, wrist and knee joints before and after treatment and the ΔDAS28 (r = 0.642, P = 0.001), ΔDAS28-CRP (r = 0.712, P < 0.001) and ΔTJC (r = 0.608, P = 0.003), respectively.Conclusion. The FDG uptake observed in the inflamed RA joints may reflect disease activity. The FDG-PET response was correlated with the clinical response to the biologic treatment of RA. [ABSTRACT FROM AUTHOR]

Background. The prevalence of esophageal cancer accompanied by hypopharyngeal cancer (HPC) is high and increasing rapidly in Asia. The purpose of this prospective study was to evaluate the prevalence of esophageal cancer during the pretreatment of HPC patients who were routinely examined using esophagogastroduodenoscopy (EGD) and 18F-fluorodeoxyglucose/computed tomography (FDG-PET/CT) and to discuss the utility of these examinations. Material and methods. Between September 2005 and September 2010, 33 patients with newly diagnosed HPC (all with squamous cell carcinoma) underwent EGD (after a conventional endoscopy, iodine staining was performed) and FDG-PET/CT examinations. We evaluated the prevalence of esophageal cancer among HPC patients according to the EGD findings and determined the sensitivity of FDG-PET/CT for the detection of esophageal primary tumors for each clinical T classification. Results. In 17 of the 33 patients (51.5%), 29 biopsy-proven esophageal squamous cell carcinomas were diagnosed using EGD. In eight of the 17 (47.1%) patients, two or more esophageal cancer lesions were diagnosed. Twenty-four of the 29 (82.8%) lesions were superficial esophageal cancers, and the remaining five (17.2%) lesions were advanced esophageal cancers. In six of the 29 (20.7%) esophageal cancer lesions that were detected using FDG-PET/CT, only one of the 29 (3.4%) lesions was evaluated as being equivocal; the remaining 22 (75.9%) lesions were not detected. The distribution of the clinical T classifications detected using FDG-PET/CT was as follows: T1a, 0/21 (0%); T1b, 1/3 (33%); and T3, 5/5 (100%). Conclusions. The prevalence of esophageal cancer during the pretreatment of HPC patients was 51.5%; this prevalence was higher than that in previous reports. We believe that the increasing proportion of superficial lesions (82.8%) detected using iodine staining and EGD may have led to the relatively high prevalence. FDG-PET/CT detected only 20.7% of the esophageal cancers, although FDG-PET/CT is capable of detecting unexpected primary malignant tumors other than esophageal cancer. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the cortical activity of 2 successful prelingually deafened adult cochlear implant (CI) users who have been trained by auditory-verbal/oral communication since childhood. Methods: Changes in regional cerebral blood flow were measured by positron emission tomography using 18F-fluorode-oxyglucose while the subjects were receiving auditory language stimuli by listening to a story. Ten normal-hearing volunteers were observed as age-matched control subjects. Results: In both cases, the auditory-related regions, when compared to same regions in the control subjects, showed hypermetabolism in the left dorsolateral prefrontal cortex and the left precentral gyrus--similar to that in successful CI users who are prelingually deafened children or postlingually deafened adults. Both subjects had the ability to activate these areas, and this ability might be one of the reasons that accounts for such exceptionally good performance in older prelingually deaf CI users. As for the visual-related regions, hypometabolism was observed in Brodmann areas 18 and 19, and this finding might be related to the intensive auditory-verbal/oral education that the subjects had received since childhood. Conclusions: Despite the limits imposed by the small sample size and the spatial resolution of positron emission tomography, this study yielded insights into the nature of the brain plasticity in prelingually deafened adults who are successful CI users. [ABSTRACT FROM AUTHOR]

The Japan Materials Testing Reactor (JMTR) is now under refurbishment, and the operation of the new JMTR will start in FY 2011. The new JMTR has a plan to produce ^99Mo, which is the parent nuclide of ^99mTc, and two ^99Mo production technologies have been developed: one is a solid irradiation method, and the other is a solution irradiation method. In the solid irradiation method, it was found that JMTR can provide about 20% of the ^99Mo imported into Japan. In the solution irradiation method, the fundamental characteristics of the aqueous molybdate solutions selected as candidates for the irradiation target were cleared by the gamma-ray irradiation test. Aiming at the domestic production of ^99Mo in Japan, the development of ^99Mo production technologies in JMTR is kept going. [ABSTRACT FROM AUTHOR]

Abstract: Background: F-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a useful tool for the detection of local inflamed atherosclerotic lesions. Objective: This study used hybrid PET/computed tomography (CT) to examine the effects of 2 doses of atorvastatin on 18F-FDG uptake in atherosclerotic plaques in Japanese adults with stable angina pectoris who were scheduled to undergo percutaneous coronary intervention (PCI). Methods: This was a prospective, randomized, investigator-blinded, open-label study in patients with dyslipidemia (total cholesterol ≥220 mg/dL and/or LDL-C ≥140 mg/dL) who were scheduled to undergo PCI for stable angina pectoris and had not received any lipid-lowering drugs within 1 year before enrollment. Patients were randomly allocated to receive atorvastatin 5 or 20 mg/d for 6 months. At baseline (the day after PCI), 18F-FDG uptake in the ascending aorta and femoral artery was determined using PET/CT imaging, and the mean target-to-background ratio (TBR) was calculated in individual plaques. The same regions were assessed by PET/CT after 6 months of treatment. Changes from baseline to follow-up in the lipid profile, serum malondialdehyde-modified LDL-C (MDA–LDL-C), and serum high-sensitivity C-reactive protein (hs-CRP) were also examined. Drug adherence, adverse events, and changes in medications were monitored at monthly outpatient visits. Results: Of 32 patients initially screened, 2 were excluded due to newly diagnosed cancer; thus, 30 patients were randomly assigned to treatment, 15 in each group. Patients were predominantly male (18 [60%]), with a mean (SD) age of 54 (11) years, mean body weight of 65 (12) kg, and mean total cholesterol, HDL-C, and triglyceride concentrations of 240 (29), 48 (14), and 180 (102) mg/dL, respectively. After 6 months, the 20-mg group had significant reductions from baseline in mean (SD) TBR in the ascending aorta (from 1.15 [0.14] to 1.05 [0.12]; percent change, −7.9% [9.4%]; P = 0.007) and the femoral artery (from 1.12 [0.11] to 1.02 [0.11]; percent change, −9.9% [13.8%]; P = 0.012). The corresponding changes from baseline were not statistically significant in the 5-mg group. The differences in percent change in TBR in the 2 locations were not significant between groups. When data from the 2 groups were combined, the overall reduction in TBR from baseline to 6 months was significant in both the ascending aorta (P = 0.003) and the femoral artery (P = 0.021). The decreases in TBR in both arteries were significantly correlated with reductions in LDL-C (ascending aorta: r 2 = 0.230 [P = 0.012]; femoral artery: r 2 = 0.338 [P = 0.003]), MDA–LDL-C (ascending aorta: r 2 = 0.183 [P = 0.028]; femoral artery: r 2 = 0.247 [P = 0.010]), and hs-CRP (ascending aorta: r 2 = 0.132 [P = 0.048]; femoral artery: r 2 = 0.271 [P = 0.007]). One patient in the 5-mg group and 2 patients in the 20-mg group had ∼2-fold increases in serum aminotransferases on a single occasion; however, no specific musculoskeletal or hepatic adverse events were observed, and aminotransferase values decreased to within normal ranges without changes in the atorvastatin dose. Conclusion: Six months of treatment with atorvastatin 20 mg, but not 5 mg, was associated with a significant reduction in TBR in the ascending aorta and femoral artery in these Japanese adults with dyslipidemia undergoing PCI for stable angina pectoris. University Hospital Medical Information Network Clinical Trials Registry identifier: C000000371. [Copyright &y& Elsevier]

Background: Incorporating mediastinoscopy (MS) into the PET-based strategy for non-small cell lung carcinoma (NSCLC) patients might be cost-effective because MS can allow unnecessary thoracotomies to be avoided. The objective of our study was to assess the cost-effectiveness of incorporating MS into a PET strategy for NSCLC patients.Methods: To determine life expectancy (LE), quality adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER), a decision-tree sensitivity analysis was designed for histopathologically confirmed NSCLC patients with M0 disease, based on the three competing strategies of chest CT only vs. PET + CT vs. PET + CT + MS. A simulation of 1000 NSCLC patients was created using baselines of other relevant variables in regard to sensitivity, specificity, mortality, LE, utilities and cost from published data. One-way sensitivity analyses were performed to determine the influences of mediastinal metastasis prevalence on LE, QALY and ICER.Results: The LE and QALY per patient in the CT only strategy, PET + CT strategy and PET + CT + MS strategy were 4.79 and 4.35, 5.33 and 4.93 and 5.68 and 5.33 years, respectively, with a 20% prevalence of mediastinal metastasis. The ICERs were 906.6 yen x 10(3) (7555 US dollars)/QALY/patient at a 20% mediastinal metastasis prevalence, and 2194 yen x 10(3) (18,282 US dollars)/QALY/patient at a 50% prevalence, but exceeded 5280 yen x 10(3) (44,000 US dollars)/QALY/ patient at 80%.Conclusions: Our study quantitatively showed the CT + PET + MS strategy in place of the PET + CT strategy in managing NSCLC patients to be cost-effective. MS should be incorporated into the PET + CT strategy for NSCLC patients except in those highly suspected of having mediastinal disease on chest CT or PET. [ABSTRACT FROM AUTHOR]

Background: Although iodine 123 15-(p-iodophenyl)-3-(R , S) methylpentadecanoic acid (BMIPP) can assess abnormal utilization of fatty acid in the diseased myocardium, the prognostic value of BMIPP imaging at rest in patients with known or suspected coronary artery disease (CAD) remains unclear.Methods and Results: A total of 270 patients were included by a retrospective search of the existing databases of 4 institutions. In addition to hard events, consisting of cardiac death and nonfatal myocardial infarction, any significant events including death, nonfatal myocardial infarction, coronary revascularization, heart failure, and unstable angina were assessed. During a median follow-up of 3.9 years, 33 patients had significant events, among whom 10 had hard events. Kaplan-Meier survival estimates revealed a hard event-free survival rate of 98% at 3 years in patients with a BMIPP defect score lower than 5 but 93% in those with a defect score of 5 or greater ( P = .03). With regard to significant events, the analysis showed an event-free survival rate of 92% at 3 years in patients with a BMIPP defect score lower than 5 but 80% in those with a defect score of 5 or greater ( P = .0003).Conclusions: These results indicate that resting BMIPP imaging has prognostic value and may have a role in the risk stratification of patients with known or suspected CAD. [ABSTRACT FROM AUTHOR]

This survey was performed to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2020 in Japan. The results are based on responses to questionnaires sent to nuclear medicine centers. Replies were obtained from 1,006 centers out of 1,212 to which the questionnaire was sent. A total of 940,758 administrations of radiopharmaceuticals were reported. There were 17 cases with adverse reactions, giving an incidence of adverse reactions of 1.8 per 100,000 cases. Two cases of defective products were reported, giving an incidence of defective products of 0.2 per 100,000 cases.

Purpose: To investigate the usefulness of the positron emission tomography response criteria in solid tumors 1.0 (PERCIST1.0) for predicting tumor response to neoadjuvant chemotherapy and prognosis and determine whether PERCIST improvements are necessary for esophageal squamous cell carcinoma (ESCC) patients., Patients and Methods: We analyzed the cases of 177 ESCC patients and examined the association between PERCIST and their pathological responses. Associations of whole-PERCIST with progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and Cox proportional hazards model. To investigate potential PERCIST improvements, we used the survival tree technique to understand patients' prognoses., Results: There were significant correlations between the pathologic response and PERCIST of primary tumor (p < 0.001). The optimal cutoff value of the primary tumors' SULpeak response to classify pathologic responses was -50.0%. The diagnostic accuracy of SULpeak response was 87.3% sensitivity, 54.1% specificity, 68.9% accuracy, positive predictive value 60.5%, and negative predictive value 84.1%. Whole-PERCIST was significantly associated with PFS and OS. The survival tree results indicated that a high reduction of the whole SULpeak response was significantly correlated with the patients' prognoses. The cutoff values for the separation of prognoses were - 52.5 for PFS and - 47.1% for OS., Conclusion: PERCIST1.0 can help predict tumor responses and prognoses. However, 18 F-FDG-PET/CT tends to underestimate residual tumors in histopathological response evaluations. Modified PERCIST, in which the partial metabolic response is further classified by the SULpeak response (-50%), might be more appropriate than PERCIST1.0 for evaluating tumor responses and stratifying high-risk patients for recurrence and poor prognosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Public knowledge-based application ("Kouchi-shinsei" in Japanese) is unique to Japan, implemented to eliminate the off-label use of unapproved indications, dosages, and administrations because of drug lag. The guidance for public knowledge-based application was issued in 1999. This study comprehensively investigated the trends of items approved by public knowledge-based application in Japan during the last 2 decades. Prescription drugs approved from January 2000 to December 2019 were surveyed. In Japan, 1,855 drugs were approved within the target survey period. Among them, 219 (11.8%) were approved by public knowledge-based application. Considering the changes in the number of items approved by public knowledge-based application over the years, the number of items approved in 2000 was 7, reaching a maximum of 34 items in 2011, and decreased after that, 8 items were approved in 2019. The regulatory characteristics of drugs approved by public knowledge-based application and those of other drugs were compared. By public knowledge-based application, more anticancer and pediatric drugs were approved (P < 0.001), and only one drug for orphan diseases was approved (P < 0.001). In addition, the review time of public knowledge-based applications was significantly shorter than that of normal applications regardless of time point. The approval system using public knowledge-based application began in 2000, following issuance of the "Guidance for off-label use of prescription drugs." Furthermore, the approved items were mostly drugs for cancer, infectious diseases, and pediatric drugs. We anticipate the promotion of public knowledge-based application to accommodate the approval of drugs for orphan diseases., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2019 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. Replies were obtained from 1,003 institutions out of 1,213 to which the questionnaire had been sent. A total of 1,037,568 radiopharmaceutical administrations were reported. Eighteen cases of adverse reactions were reported. The incidence of adverse reactions per 100,000 cases was 1.7. No case of defective products was reported.

Aim: Many researchers argue that Alzheimer's disease is at least partly caused by deposition of amyloid beta (Aβ) in the brain. Ferulic acid (FA) and Angelica archangelica (AA) are candidate agents for reducing Aβ and improving cognitive function. Feru-guard 100M is a supplement containing FA and AA extract. Using this supplement, we planned to assess the effect of FA and AA on Aβ deposition in the human brain., Methods: This was an open-label, interventional multi-institutional joint study of Kobe University and the Institute of Biomedical Research and Innovation (Kobe, Japan). Seventeen subjects diagnosed with mild cognitive impairment were divided into two groups: the intervention group (n = 10) and the control group (n = 7). The subjects in the intervention group used Feru-guard 100M every day for 48 weeks, whereas the subjects in the control group did not use the supplement. We assessed the differences between the two groups by examining Aβ deposition and brain atrophy at 48 weeks and cognitive function every 24 weeks. We used carbon-11-labelled Pittsburgh compound B (PiB) positron emission tomography to evaluate Aβ deposition., Results: There were no significant differences in Aβ deposition, brain atrophy, and cognitive function between the two groups. Specifically, differences in Aβ deposition change in seven regions of interest examined with PiB positron emission tomography, brain atrophy change in four indicators of voxel-based morphometry, and cognitive impairment measured by five psychological tests were not significantly between the two groups., Conclusion: Treatment with Feru-guard 100M, a supplement containing FA and AA extract, for 48 weeks did not reduce cortical PiB retention, which reflects Aβ deposition. It also did not suppress the aggravation of brain atrophy or decline in cognitive function., (© 2020 Japanese Psychogeriatric Society.)

Objective: The prognostic value of harmonized pretreatment volume-based quantitative fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) parameters in metastatic breast cancer patients was investigated., Subjects and Methods: Records of 65 stage IV breast cancer patients, including 29 estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, 23 HER2-positive, and 13 triple-negative cases, from four different institutions were retrospectively reviewed. Harmonized standardized uptake value (SUVmax) of the primary tumor (pSUVmax), highest SUVmax of all malignant lesions (wSUVmax), whole-body metabolic tumor volume (WB MTV), and whole-body total lesion glycolysis (WB TLG) shown by pretreatment 18 F-FDG PET/CT imaging were calculated. Cox proportional hazards model and log-rank test results were used to evaluate relationships among clinicopathological factors, volume-based quantitative 18 F-FDG PET/CT parameters, progression-free survival, and overall survival (OS)., Results: Disease progression occurred in 54 patients and 28 died during a median follow-up period of 52.5 months (range 2.6-133.6 months). Univariate analysis of all cases showed associations of negative ER and progesterone receptor (PR) status (P=0.0025), and high T/N stage (P=0.037/P=0.019), pSUVmax (P=0.049), WB MTV (P=0.021), and WB TLG (P=0.0010) with significantly shorter OS. Multivariate analysis confirmed negative ER and PR status (hazard ratio [HR]: 6.42, 95% confidence interval [CI]: 2.27-19.38; P=0.0054), high T stage (HR: 5.10, 95% CI:1.96-18.61, P=0.0064) and WB TLG (HR: 4.69, 95% CI:1.67-12.79, P=0.049) as independent negative OS predictors. In two groups of ER-positive/HER2-negative and triple-negative, WB TLG had a significant association with death (P=0.021 and P=0.037, respectively) on univariate analysis. In a HER2-positive group, no independent negative OS predictors were observed., Conclusion: In metastatic breast cancer patients, harmonized pretreatment quantitative volume-based 18 F-FDG PET/CT parameters, especially whole-body TLG, are potential surrogate markers for prognosis.

Objective: This pharmacovigilance-based survey was aimed at determining the prevalence of, and association between, radiopharmaceuticals and adverse reactions to radiopharmaceuticals from 1975 to 2017 in Japan., Methods: The Subcommittee for Safety Issues of Radiopharmaceuticals of the Japan Radioisotope Association's Medical Science and Pharmaceutical Committee mailed a form for reporting adverse reactions to radiopharmaceuticals to all institutes performing nuclear medicine examinations in Japan. This investigation included adverse reactions to diagnostic radiopharmaceuticals labeled with both single-photon- and positron-emitting radionuclides and therapeutic sodium iodide labeled with 131 I. Each institute returned the reporting form to the subcommittee each time an adverse reaction occurred., Results: Replies were obtained from 75% of the institutions. In total, 1099 adverse reactions were reported from 46,645,580 radiopharmaceutical administrations, giving a prevalence of 2.4 adverse reactions per 100,000 administrations (95% confidence interval 2.2-2.5). Adverse reactions were most frequently observed for 131 I-iodomethylnorcholesterol (230.1/10 5 administrations), followed by 131 I-HSA (76.3/10 5 administrations), 131 I-sodium iodohippurate (31.2/10 5 administrations), and 99m Tc-DTPA (12.0/10 5 administrations). Comparison of adverse reactions between before and after 1997 revealed that prevalence dropped from 3.7/10 5 administrations (95% confidence interval 3.5-4.1) to 1.5/10 5 administrations (95% confidence interval 1.4-1.6). During the study period, vasovagal reactions accounted for 50.3% of adverse reactions, fever for 7.5%, allergic reactions for 25.7%, and other for 16.5%; 3.7% of all adverse reactions were considered severe but none were lethal. A definite, probable, possible, less likely, and uncertain causal relationship with radiopharmaceuticals was observed in 13.1%, 33.7%, 39.9%, 6.2%, and 7.1% of adverse reactions, respectively., Conclusions: These results suggest that nuclear medicine staff must be aware of the possibility of adverse reactions from radiopharmaceuticals, despite their rarity.

Aim: Recently, nuclear cardiology has dramatically advanced by a new technology development such as the device, short-term acquisition system, image reconstruction algorithm and image analysis. Although these innovations have been gradually employed in routine examinations, we did not investigate the current use of image acquisition, image reconstruction, and image analysis with myocardial perfusion single-photon emission computed tomography (MPS). We investigated the current status of MPS imaging technology in Japan., Methods: We carried out a survey using a Web-based questionnaire system, the opening of which was announced via e-mail, and it was available on a website for 3 months. We collected data on the current use of MPS with 201 Tl and/or 99m Tc agents with respect to routine protocols, image acquisition, image reconstruction, and image analysis., Results: We received responses to the Web-based questionnaire from 178 and 174 people for 99m Tc and 201 Tl MPS, respectively. The routine protocols of MPS of stress-rest and rest-stress MPS on 1-day protocols with 99m Tc were 41.2% and 14.5%, respectively, and the rest-only scan response rate was 23.7%, whereas that of 201 Tl MPS was 65.9% with stress-rest MPS, 19.0% with rest-only MPS, and 10.9% with stress-rest MPS adding a rest scan 24 h after injection. The filtered back projection (FBP) method is most commonly used image reconstruction method, yielding 70.5% for 99m Tc MPS and 76.8% for 201 Tl MPS, including combined FBP and ordered subset expectation maximization method. The results for no-correction (NC) images were 49.2% with 99m Tc MPS and 55.2% with 201 Tl MPS including the response of NC and combined attenuation correction (AC) and scatter correction (SC) (i.e., ACSC) images. The AC or ACSC images of 99m Tc and 201 Tl were provided by 30-40% of the institutions surveyed., Conclusions: We investigated the current status of MPS imaging technology in Japan, and found that although the use of various technical developments has been reported, some of these technologies have not been utilized effectively. Hence, we expect that nuclear medicine technology will be used more effectively to improve diagnosis.

Aim: To examine whether Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) is useful to predict tumour response and prognosis of patients with oesophageal cancer who received neoadjuvant chemoradiotherapy (NACRT) followed by surgery., Materials and Methods: This multicentre retrospective study included 60 patients with oesophageal cancer who underwent 2-[ 18 F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography ( 18 F-FDG-PET/CT) before and after NACRT prior to surgery from January 2007 and June 2016. The correlation between pathological response and PERCIST was assessed by χ 2 test. The prognostic significance was assessed by the Kaplan-Meier method and Cox regression analysis., Results: There were 30 responders and 30 non-responders pathologically. The complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) were seen in 22, 29, seven, and two patients, respectively. There was a significant correlation between pathological response and PERCIST (p<0.001). Forty patients showed eventual progression, and 20 patients were alive without progression between the start of NACRT and last clinical follow-up (median follow-up period; 27 months [range, 3-107]). Pathological stage and PERCIST were significant for progression-free survival (PFS; p=0.044 and 0.006, respectively) and also significant for overall survival (OS; p=0.009 and 0.001, respectively) at univariate analysis. Pathological lymph node staging was also significant for OS at univariate analysis (p=0.018). At multivariate analysis, PERCIST remained significant and independent for PFS (hazard ratio [HR]: 1.59, p=0.046) and OS (HR: 1.82, p=0.008)., Conclusion: PERCIST may be useful for predicting tumour response and prognosis of patients with oesophageal cancer who received NACRT., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Cardiac denervation is associated with progressive left ventricular (LV) dysfunction, ventricular arrhythmias, and sudden cardiac death (SCD) in heart failure (HF). In this regard, it is important to evaluate cardiac-specific sympathetic nervous system (SNS) function. The radiotracer Iodine-123 meta-iodobenzylguanidine ( 123 I-mIBG) can noninvasively evaluate pre-synaptic SNS function. Recent multicenter trials have shown 123 I-mIBG to have strong predictive value for fatal arrhythmias and cardiac death in HF. 123 I-mIBG was initially developed in the USA in the 1970s. In 1992, the Japanese Ministry of Health and Labour approved 123 I-mIBG for the assessment of cardiac function. Following approval, the Japanese nuclear cardiology community developed 123 I-mIBG imaging services in various medical centers. Japanese groups have been trying to establish the clinical utility of 123 I-mIBG and standardize parameters for data acquisition and image analysis. The US Food and Drug Administration (FDA) has approved clinical use of 123 I-mIBG for cardiac and non-cardiac imaging. However, clinical use of 123 I-mIBG in the US has been very limited. The number of 123 I-mIBG studies in Japan has also been limited. There are similarities and differences between the two countries. To establish the clinical utility of 123 I-mIBG in both countries, it is important to characterize the situations of 123 I-mIBG in each.

Introduction: Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA., Methods: We performed [ 123 I] FP-CIT SPECT and [ 123 I] N-isopropyl-p-iodoamphetamine SPECT (IMP-SPECT), and determined GBA expression and glucocerebrosidase (GCase) activity in leukocytes in two GBA-associated PD patients and nine unaffected individuals (including four mutation carriers) in a Japanese family with a heterozygous gross deletion mutation in the GBA gene., Results: The two PD patients and two of the four clinically unaffected carriers showed decreased [ 123 I] FP-CIT uptake. IMP-SPECT showed a pattern like that in DLB in one patient. When we compared PD patients with GBA mutations with clinically unaffected carriers, there was a poor correlation between the development of PD and the expression level of GBA or GCase activity., Conclusion: We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [ 123 I] FP-CIT in this family. However, since we cannot conclude whether a reduction of GCase activity is directly correlated with the pathogenesis of PD or not, longitudinal follow-up of this family is needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: In 2013, the Japanese Society of Nuclear Medicine (JSNM) announced consensus guidelines for pediatric nuclear medicine. These JSNM guidelines proposed use of lower administered doses compared with traditionally determined doses, which were estimated from age, weight or body surface area (BSA) based on the administered dose for adults in Japan. When the JSNM guidelines are used, the relationship between this recommended administered dose and image quality remains unclear. In this study, we clarified the relationship between administered dose and image quality for pediatric 99m Tc-DMSA renal scan retrospectively, and verified the diagnosable image quality with the recommended administered dose of the JSNM guidelines., Materials and Methods: Data from 7 pediatric patients who underwent 99m Tc-DMSA dynamic renal scans according to the guidelines' recommended doses were collected. Scan frame rate was 1 frame/min, and scan time was up to 8 min. Eight images, which had different acquired time periods from 1 min to 8 min were prepared by adding each frame. Nine nuclear medicine specialists determined 8 images with different acquired times as diagnosable or undiagnosable. A region of interest (ROI) with 50% thresholds was placed on each kidney of every image. Coefficient of variation (CV) was calculated by dividing the standard deviation (σ) by the mean counts (µ) of each ROI (CV = σ/µ × 100). 99m Tc-DMSA renal scans (total of 2821 cases) that were performed previously in collaboration with 6 hospitals were collected, and CVs of these images were calculated in all cases. These 2821 cases were separated into 5 groups for every 10 kg weight; i.e., (1) less than 10 kg, (2) 10-19.9 kg, (3) 20-29.9 kg, (4) 30-39.9 kg, and (5) above 40 kg. Regression line of each group was analyzed in relation to the CV and administered dose. The CV at the point of intersection with the recommended dose range from the guideline was determined for each group. This CV value was considered as the estimated CV of the image obtained when the recommended dose of the guideline was used. Thus, if the CV was equal to or less than the estimated CV value, then the diagnostic image quality was deemed satisfactory., Results: Average CV of the lower limit of diagnosable images in 7 cases as determined by 9 nuclear medicine specialists was 19.9%. Estimated CV was 21.2-24.2% in the group weighing < 10 kg (group 1), 19.9-20.6% in the group weighing > 10 kg and < 20 kg (group 2), 19.6% in group weighing > 20 kg and < 30 kg (group 3), 19.4-19.5% in the group weighing > 30 kg and < 40 kg (group 4), and 19.8% in the group weighing > 40 kg (group 5). The estimated CVs from groups 1 and 2 with weight < 20 kg exceeded 19.9%., Conclusions: Although 99m Tc-DMSA renal scan can be carried out using the guidelines' recommended dose with conventional image acquisition time in patients weighing 20 kg or more, those < 20 kg need consideration for a longer image acquisition time to obtain diagnosable images.

Objective: To examine the correlation of the quantitative indexes standardized uptake value (SUV), SUV corrected for lean body mass (SUL) and SUV corrected for Japanese lean body mass (SULj) with body weight to develop an appropriate quantitative index independent of body weight fluctuation for assessment of response to cancer treatment in Japanese patients., Subjects and Methods: Fifty-six males with esophageal cancer and 30 females with breast cancer underwent fluorine-18-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) scans, once before and once after, receiving neoadjuvant chemotherapy prior to planned surgical resection. The maximum value, peak value, and average value of SUV, SUL and SULj were calculated by setting a spherical volume of interest (3cm diameter) in a normal area of the liver. The correlation between each index and body weight was obtained from the correlation coefficient (r) and the significance of the correlation was tested., Results: Analyses were conducted with all patients (P<0.01), as well as after dividing into those with only esophageal (P<0.05) or breast (P<0.01) cancer. Regarding the correlation coefficient between each index and body weight, a significant difference was seen for SUVmax, SUVpeak and SUVmean. In contrast, there was no correlation with body weight for SULmax, SULpeak, SULmean, SULjmax, SULjpeak, or SULjmean in any of the 3 groups., Conclusion: Based on the correlation with body weight, we concluded that both SUL and SULj (SUL corrected for Japanese lean body mass) is useful for assessment of cancer treatment response in Japanese patients.

Purpose: In an Asian international multicenter phase II trial conducted in patients with peripheral T-cell lymphoma (PTCL), [F-18]FDG-PET/CT was used for evaluation of the therapeutic response. Standardization of the PET/CT scanners was necessary before patient enrollment. We therefore standardized the scanners by phantom tests based on the profile approved by the Quantitative Imaging Biomarkers Alliance (QIBA) of Radiological Society of North America (RSNA)., Materials and Methods: The tests were conducted on 12 scanners in 12 facilities in compliance with the QIBA Profile and used National Electrical Manufacturers Association (NEMA) International Electrotechnical Commission (IEC) body phantoms. We measured three parameters (standardized uptake value [SUV], resolution and noise) and adjusted the imaging parameter values. The indexes recommended in the Japanese Society of Nuclear Medicine (JSNM) guideline were also evaluated., Results: In a total of 12 facilities, 6 facilities required no change in imaging conditions and 6 facilities required changes in imaging parameters. After revision, the three measurements (SUV, resolution and noise) met QIBA criteria at all sites, but 10 of the 12 scanners did not meet JSNM criteria., Conclusion: We standardized imaging conditions using phantoms as required in the RSNA-QIBA profile for response evaluation by [F-18]FDG PET/CT images in a multicenter study.

Purpose: An artificial neural network (ANN) has been applied to detect myocardial perfusion defects and ischemia. The present study compares the diagnostic accuracy of a more recent ANN version (1.1) with the initial version 1.0., Methods: We examined 106 patients (age, 77 ± 10 years) with coronary angiographic findings, comprising multi-vessel disease (≥ 50% stenosis) (52%) or old myocardial infarction (27%), or who had undergone coronary revascularization (30%). The ANN versions 1.0 and 1.1 were trained in Sweden (n = 1051) and Japan (n = 1001), respectively, using 99m Tc-methoxyisobutylisonitrile myocardial perfusion images. The ANN probabilities (from 0.0 to 1.0) of stress defects and ischemia were calculated in candidate regions of abnormalities. The diagnostic accuracy was compared using receiver-operating characteristics (ROC) analysis and the calculated area under the ROC curve (AUC) using expert interpretation as the gold standard., Results: Although the AUC for stress defects was 0.95 and 0.93 (p = 0.27) for versions 1.1 and 1.0, respectively, that for detecting ischemia was significantly improved in version 1.1 (p = 0.0055): AUC 0.96 for version 1.1 (sensitivity 87%, specificity 96%) vs. 0.89 for version 1.0 (sensitivity 78%, specificity 97%). The improvement in the AUC shown by version 1.1 was also significant for patients with neither coronary revascularization nor old myocardial infarction (p = 0.0093): AUC = 0.98 for version 1.1 (sensitivity 88%, specificity 100%) and 0.88 for version 1.0 (sensitivity 76%, specificity 100%). Intermediate ANN probability between 0.1 and 0.7 was more often calculated by version 1.1 compared with version 1.0, which contributed to the improved diagnostic accuracy. The diagnostic accuracy of the new version was also improved in patients with either single-vessel disease or no stenosis (n = 47; AUC, 0.81 vs. 0.66 vs. p = 0.0060) when coronary stenosis was used as a gold standard., Conclusion: The diagnostic ability of the ANN version 1.1 was improved by retraining using the Japanese database, particularly for identifying ischemia.

Purpose: The AI-300 automated infusion device (Sumitomo Heavy Industries, Ltd., Tokyo, Japan) is subject to administration error as a function of smaller volumes of 18 F-FDG dispensed via a three-way cock supplied with a disposable kit. The present study aimed to validate the administration accuracy of the AI-300 using an improved disposable kit for quantitative positron emission tomography (PET) assessment., Methods: We determined administration accuracy between the improved and previous disposable kits by measuring variations in dispensed volumes and radioactive concentrations of 18 F-FDG according to the criteria of the Japanese Society of Nuclear Medicine. A reference value was generated by measuring radioactivity using a standard dose calibrator., Results: The values obtained using the previous kit deviated from the reference values by a maximum of -10.6%, and the deviation depended on dispensed volumes of 18 F-FDG<0.25 mL. In contrast, the values were relatively stable when using the improved kit with dispensed 18 F-FDG volumes < 0.25 mL. Variations in radioactive concentrations were relatively stable using the improved kit, whereas that of the previous kit was slightly unstable at high radioactive concentrations., Conclusion: The administration accuracy of the AI-300 using the previous kit varied considerably according to smaller dispensed volumes, but the improved kit might alleviate this problem. The present results indicated that the improved disposal kit should be immediately implemented to eliminate uncertainty surrounding quantitative PET findings.

Purpose: This article discusses possible supplemental breast cancer screening modalities for younger women with dense breasts from a perspective of population-based breast cancer screening program in Japan., Conclusion: Supplemental breast cancer screening modalities have been proposed to increase the sensitivity and detection rates of early stage breast cancer in women with dense breasts; however, there are no global guidelines that recommend the use of supplemental breast cancer screening modalities in such women. Also, no criterion standard exists for breast density assessment. Based on the current situation of breast imaging in Japan, the possible supplemental breast cancer screening modalities are ultrasonography, digital breast tomosynthesis, and breast magnetic resonance imaging. An appropriate population-based breast cancer screening program based on the balance between cost and benefit should be a high priority. Further research based on evidence-based medicine is encouraged. It is very important that the ethnicity, workforce, workflow, and resources for breast cancer screening in each country should be considered when considering supplemental breast cancer screening modalities for women with dense breasts.

Low-energy characteristic x-rays emitted by 111 In and 123 I sources are easily absorbed by the containers of the sources, affecting radioactivity measurements using a dose calibrator. We examined the effects of different containers on the estimated activities. The radioactivities of 111 In, 123 I, 201 Tl, and 99m Tc were measured in containers frequently employed in clinical practice in Japan. The 111 In measurements were performed in the vials A and B of the 111 In-pentetreotide preparation kit and in the plastic syringe. The activities of 123 I-metaiodobenzylguanidine and 201 Tl chloride were measured in the prefilled glass syringes and plastic syringes. The milking vial, vial A, vial B, and plastic syringe were used to assay 99m Tc. For 111 In and 123 I, measurements were performed with and without a copper filter. The filter was inserted into the well of the dose calibrator to absorb low-energy x-rays. The relative estimate was defined as the ratio of the activity estimated with the dose calibrator to the standard activity. The estimated activities varied greatly depending on the container when 111 In and 123 I sources were assayed without the copper filter. The relative estimates of 111 In were 0.908, 1.072, and 1.373 in the vial A, vial B, and plastic syringe, respectively. The relative estimates of 123 I were 1.052 and 1.352 in the glass syringe and plastic syringe, respectively. Use of the copper filter eliminated the container-dependence in 111 In and 123 I measurements. Container-dependence was demonstrated in neither 201 Tl nor 99m Tc measurements. The activities of 111 In and 123 I estimated with a dose calibrator differ greatly among the containers. Accurate estimation may be attained using the container-specific correction factor or using the copper filter.

Background: The presence of cardiac involvement in sarcoidosis, a multisystem granulomatous disease of unknown etiology, is associated with very poor prognosis. Therefore, early detection of cardiac sarcoidosis (C-sar) is very important for effective treatment. Recently, the value of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), which allows visualization of even minute amounts of myocardial damage, has been emphasized in diagnosing C-sar. Although the presence of LGE has been added as a minor criterion for diagnosing C-sar in the most recent Japan Ministry of Health and Welfare (JMHW) guidelines, its clinical utility remains unknown., Methods: A total of 17 patients with biopsy-proven extracardiac sarcoidosis, who underwent CMR and examinations using a sufficient number of modalities to diagnose or exclude C-sar in accordance with the JMHW diagnostic criteria, were retrospectively enrolled in this study. Among these 17 patients, 7 patients were diagnosed with C-sar and 10 with non-C-sar. We investigated the clinical performance of LGE in the detection of cardiac involvement, compared the distribution of LGE with perfusion defects of iodine-123-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) or thallium-201 (201Tl) scintigraphy, and evaluated the prognostic value of LGE on CMR in identifying adverse clinical events., Results: All patients diagnosed with C-sar were positive for LGE and all diagnosed with non-C-sar patients were negative. Evaluation of LGE revealed a broader range of abnormalities than the evaluation of the defects shown by either BMIPP or 201Tl scintigraphy. All adverse events occurred in the C-sar patients with LGE., Conclusions: This study showed that LGE is useful for the detection of cardiac involvement, and it might be a promising tool for determining the prognosis of patients with biopsy-proven extracardiac sarcoidosis.

Iron deficiency and cardiac sympathetic impairment play a role in the worsening of heart failure, and these two conditions may be linked. The present study aimed to clarify the relationship between myocardial iron deficiency, cardiac sympathetic activity, and major adverse cardiac events (MACE) in patients with dilated cardiomyopathy (DCM). Cardiac T2* MRI for iron deficiency and (123)I-Metaiodobenzylguanidine (MIBG) imaging for cardiac sympathetic activity were performed in 46 patients with DCM. Myocardial T2* value (M-T2*) was calculated by fitting signal intensity data for mid-left ventricular septum to a decay curve using 3-Tesla scanner. (123)I-MIBG washout rate (MIBG-WR) was calculated using a polar-map technique with tomographic data. We analyze the ability of M-T2* and MIBG-WR to predict MACE. MIBG-WR and M-T2* were significantly greater in DCM patients with MACE than in patients without MACE. Receiver-operating-characteristics curve analysis showed that the optimal MIBG-WR and M-T2* thresholds of 35 % and 28.1 ms, and the two combination predict MACE with C-statics of 0.69, 0.73, and 0.82, respectively. Patients with MIBG-WR <35 % and M-T2* <28.1 ms had significantly lower event-free rates than those with MIBG-WR ≥35 % or M-T2* ≥28.1 ms (log-rank value = 4.35, p < 0.05). Cox hazard regression analysis showed that χ(2) and the hazard ratio were 3.99 and 2.15 for development of MACE in patients with MIBG-WR ≥35 % or M-T2* ≥28.1 ms (p < 0.05). Iron deficiency, expressed by a high M-T2*, and MIBG-WR were both independent predictors of MACE in patients with DCM. The two combination was a more powerful predictor of MACE than either parameter alone.

Background: Whole-body cancer screening with multimodalities including [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) detects a wide range of tumors. This program has been recognized as an option for opportunistic screening, particularly in Japan. However, reports on diagnostic accuracy have been limited. We aimed to evaluate the detectability and related properties of this screening program among asymptomatic individuals in a community setting., Methods: The study participants were 1,762 residents of Osaka Prefecture, Japan, who underwent opportunistic cancer screening at Higashitemma Clinic for the first time between November 2004 and December 2005. FDG-PET cancer screening was performed with several imaging modalities (e.g., FDG-PET, computed tomography, magnetic resonance imaging and ultrasonography) and fecal occult blood test. Screening records were linked to the Osaka cancer registry within 1 year after the screening to determine sensitivity, specificity and positive predictive values., Results: After excluding 12 participants with cancer detected before the screening, 33 were identified by the cancer registry to have primary cancers. Of these, the present screening program found that 28 were positive (6 prostate, 5 lung, 5 colorectal, 5 thyroid, 3 liver and 4 others). Sensitivity, specificity and positive predictive values were 84.8 % (28/33, 95 % confidence interval 69.1-93.3), 86.8 % (1,491/1,718, 85.1-88.3) and 10.1 % (28/277, 6.4-12.9), respectively., Conclusions: FDG-PET cancer screening with multimodalities reasonably and accurately detects existing asymptomatic cancer. However, the numbers of false negatives and false positives were not insignificant. Facilities that provide the screening should inform participants of relevant information, including the limitations of this program.

Objective: The Subcommittee on the Survey of Nuclear Medical Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years., Methods: The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2012, to all the nuclear medicine institutes. The total numbers for the year 2012 were then estimated., Results: A total of 1,167 institutes responded to the survey, including the 14 in vitro assay institutes and 266 PET centers. The recovery rate was 92 %. The number of gamma cameras installed was 1,425 in total, with 9 % decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 84 and 10.5 %, respectively. The number of single-photon tracer studies in 2012 was 1.15 million which means decrease in 19 % in 5 years and 29 % in 10 years. All but cerebral perfusion study and sentinel lymphoscintigraphy have decreased. Bone scintigraphy was a leading examination (38.7 %), followed by cardiac studies (29.4 %) and cerebral perfusion study (18.5 %) in order. SPECT studies showed an increase from 42.3 to 47.2 %. PET centers have also increased from 212 to 295, as compared to the last survey. The 135 PET centers have installed one or two in-house cyclotrons. PET studies showed 25.5 % increase in 5 years, with oncology accounting for 96.3 %. (18)F-FDG accounted for 98.2 % (505,990 examinations). PET examinations using (11)C-methionine have been increasing, with 3,352 examinations in 2012. The number of new PET studies using (11)C-PIB PET was 695. (131)I-radioiodine targeted therapies showed an increase, including 3,644 patients (53.6 %) for thyroid cancer and 4,889 patients (17.9 %) for hyperthyroidism. Out-patient thyroid bed ablation therapy with 30 mCi of (131)I accounted for 21.0 % of cancer patients. The number of admission rooms decreased from 158 to 135 in 5 years. In vitro radioassays have been declining continuously since 1992, with the number of studies of 9.0 million in 2012., Conclusions: Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study in the oncology field and radionuclide targeted therapy have steadily increased.

Purpose: Recent advances in image diagnostic technology have enhanced the discovery of peripheral small size lung cancers. Here, we examined the utility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of grade of tumor malignant potency., Methods: Seventy-nine patients with peripheral small lung cancers (≤2 cm) who underwent surgical resections and preoperative FDG-PET were enrolled. The correlations between the maximum standardized uptake value (SUVmax) and various clinicopathological features related to tumor invasiveness, nodal metastasis, and recurrence were analyzed., Results: The median SUVmax of all tumors was 2.4 (range, 0-16.1). The SUVmax was significantly higher in patients with vascular invasion (5.6 ± 3.5 vs. 2.4 ± 2.4; P <0.0001), lymphatic invasion (4.9 ± 3.7 vs. 2.7 ± 2.6; P = 0.0029), lymph node metastasis (6.1 ± 4.4 vs. 3.0 ± 2.7; P = 0.0022), and recurrences (5.8 ± 3.3 vs. 3.1 ± 3.1; P = 0.0219). Patients with SUVmax ≥2.5 had a significantly higher incidence rate of vascular invasion (56% vs. 7%; P <0.0001), lymphatic invasion (51% vs. 15%; P = 0.0006), lymph node metastasis (26% vs. 3%; P = 0.0033), and recurrence (18% vs. 3%; P = 0.0289). The patients with SUVmax ≥1.5 also had a significantly higher incidence of vascular invasion, lymphatic invasion, lymph node metastasis, and recurrence. It is particularly worth noting that patients with SUVmax <1.5 had no vascular invasion, lymph node metastasis, or recurrence., Conclusion: Preoperative SUVmax of peripheral small lung cancers were significantly associated with tumor malignancy.

Objective: Our objective was to compare the oncologic outcomes of lobectomy and segmentectomy for clinical stage IA lung adenocarcinoma., Methods: We examined 481 of 618 consecutive patients with clinical stage IA lung adenocarcinoma who underwent lobectomy or segmentectomy after preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computed tomography. Patients (n = 137) who underwent wedge resection were excluded. Lobectomy (n = 383) and segmentectomy (n = 98) as well as surgical results were analyzed for all patients and their propensity score-matched pairs., Results: Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between patients undergoing lobectomy (3-year RFS, 87.3%; 3-year OS, 94.1%) and segmentectomy (3-year RFS, 91.4%; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.27-1.20; P = .14; 3-year OS, 96.9%; HR, 0.49; 95% CI, 0.17-1.38; P = .18). Significant differences in clinical factors such as solid tumor size (P < .001), maximum standardized uptake value (SUVmax) (P < .001), and tumor location (side, P = .005; lobe, P = .001) were observed between both treatment groups. In 81 propensity score-matched pairs including variables such as age, gender, solid tumor size, SUVmax, side, and lobe, RFS and OS were similar between patients undergoing lobectomy (3-year RFS, 92.9%, 3-year OS, 93.2%) and segmentectomy (3-year RFS, 90.9%; 3-year OS, 95.7%)., Conclusions: Segmentectomy is suitable for clinical stage IA lung adenocarcinoma, with survivals equivalent to those of standard lobectomy., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)