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Objective Extracorporeal shock wave lithotripsy (ESWL) has been used to treat pancreatolithiasis in patients with chronic pancreatitis (CP), but the high recurrence rate remains challenging. We therefore evaluated the association between body composition parameters and the prediction of retreatment after ESWL. Methods This study retrospectively evaluated 42 patients with CP who had been treated with ESWL between 2008 and 2019 in a single center. Body composition parameters were measured on pretreatment computed tomography images. Patients who underwent repeat ESWL were classified as the retreatment group. Results There were 13 (31.0%) and 29 (69.0%) patients in the retreatment and non-retreatment groups, respectively. The visceral-to-subcutaneous adipose tissue area ratio (VSR) of the retreatment group was significantly lower than that of the non-retreatment group (p=0.016). When divided by the median VSR, 10 of the 20 patients with a VSR of0.85 underwent retreatment, whereas 3 of the 22 patients with a VSR of ≥0.85 underwent retreatment (p=0.019). According to a multivariate analysis, the VSR (p=0.010) and age (p=0.037) were independent factors associated with retreatment after ESWL. Conclusion This study showed that the VSR can predict the retreatment of patients with CP after ESWL.

Purpose This study aimed to investigate risk factors for radiation pneumonitis (RP) caused by electron beam (EB) boost irradiation during breast-conserving therapy. Methods and Materials This single-institution retrospective study included patients with breast cancer treated with breast-conserving therapy from 2013 to 2019. Radiation therapy comprised whole-breast irradiation with a dose of 50 Gy and 10 Gy EB boost dose to the tumor bed. EB energies were 4, 6, 9, 12, and 15 MeV. The lung volume receiving ≥1.25 Gy (V1.25) was calculated and considered because the EB energies have a short range. All patients underwent computed tomography and positron emission tomography/computed tomography within 1 year of irradiation. Imaging evaluation was based on the Common Terminology Criteria for Adverse Events, version 5.0. Results Overall, 105 patients (median age, 62 years; range, 33-85) were included for analysis with a median follow-up period of 5 months. Average area of EB boost irradiation was 72 cm2 (range, 36-196). Grade 1 RP developed in the EB irradiation field in 22 (20.6%) patients; grade 2 RP developed in 1 (0.93%) patient. Even in patients with central lung distance (CLD) ≥1.8 cm, a positive correlation was found between RP and both energy (r = 0.36; P = .005) and V1.25 (r = 0.26; P = .04). No correlation was found between RP and irradiation field size (P = .47). The EB energy and V1.25 cutoff values were 12 MeV and 24 cm3, respectively. Conclusions CLD of ≥1.8 cm, EB energy of ≥12 MeV, and V1.25 of ≥24 cm3 were risk factors associated with RP. Although the frequency of severe RP was not high, patients receiving high-energy electron treatment and those with a large CLD should be closely monitored.

The aim of this multicenter prospective study was to compare the sensitivity of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of 67Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO). The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by 67Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and 67Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and 67Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient’s attending physician. The clinical impacts (four grades) of FDG-PET/CT and 67Ga-SPECT on the final diagnosis were evaluated. A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study’s analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1–58.2%) was significantly higher than that for 67Ga-SPECT (25%, 95% CI 15.5–37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for 67Ga-SPECT (57%, P

Our objective was to investigate the differences in texture features between step-and-shoot (SS) and continuous-bed-motion (CBM) imaging in phantom and clinical studies. Methods: A National Electrical Manufacturers Association body phantom was filled with 18F-FDG solution at a sphere-to-background ratio of 4:1. SS and CBM were performed using the same acquisition duration, and the data were reconstructed using 3-dimensional ordered-subset expectation maximization with time-of-flight algorithms. Texture features were extracted using the software LIFEx. A volume of interest was delineated on the 22-, 28-, and 37-mm spheres with a threshold of 42% of the maximum SUV. The voxel intensities were discretized using 2 resampling methods, namely a fixed bin size and a fixed bin number discretization. The discrete resampling values were set to 64 and 128. In total, 31 texture features were calculated with gray-level cooccurrence matrix (GLCM), gray-level run length matrix, neighborhood gray-level different matrix, and gray-level zone length matrix. The texture features of the SS and CBM images were compared for all settings using the paired t test and the coefficient of variation. In a clinical study, 27 lesions from 20 patients were examined using the same acquisition and image processing as were used during the phantom study. The percentage difference (%Diff) and correlation between the texture features from SS and CBM images were calculated to evaluate agreement between the 2 scanning techniques. Results: In the phantom study, the 11 features exhibited no significant difference between SS and CBM images, and the coefficient of variation was no more than 10%, depending on resampling conditions, whereas entropy and dissimilarity from GLCM fulfilled the criteria for all settings. In the clinical study, the entropy and dissimilarity from GLCM exhibited a low %Diff and excellent correlation in all resampling conditions. The %Diff of entropy was lower than that of dissimilarity. Conclusion: Differences between the texture features of SS and CBM images varied depending on the type of feature. Because entropy for GLCM exhibits minimal differences between SS and CBM images irrespective of resampling conditions, entropy may be the optimal feature to reduce the differences between the 2 scanning techniques.

We conducted a randomized placebo-controlled double-blind 24-week trial using Melissa officinalis (M. officinalis) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer’s disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or M. officinalis extract group. No differences in vital signs or physical and neurologic examination results were detected between the M. officinalis and placebo groups. No serious adverse events occurred. There were no significant differences in cognitive measures; however, the mean Neuropsychiatric Inventory Questionnaire (NPI-Q) score improved by 0.5 points in the M. officinalis group and worsened by 0.7 points in the placebo group between the baseline and 24-week visit, indicating a significant difference (P = 0.012). No significant differences were apparent in disease-related biomarkers between the groups. M. officinalis extract containing 500 mg of RA taken daily was safe and well-tolerated by patients with mild dementia due to AD. Our results suggest that RA may help prevent the worsening of AD-related neuropsychiatric symptoms.Trial registration: The registration number for this clinical trial is UMIN000007734 (16/04/2012).

Parenteral nutrition-associated liver disease (PNALD) causes hepatic steatosis and moderate liver enzyme elevation due to lack of enteral nutrition and deficiency of some nutrients. However, the period for recovery from PNALD after a nutritional intervention is unknown with no report. Herein, we report a case of a 44-year-old Japanese woman with severe fatty infiltration of the liver due to malnutrition. Our nutritional support team administered appropriate total parenteral, especially fat and carnitine, nutrition to improve her malnutrition. Chronological changes in liver-to-spleen attenuation ratio were also considered because of her disease state. Computed tomography demonstrated improved attenuation of the liver, and the liver enzymes level normalized after 5 weeks from appropriate nutrition. Understanding the nutritional condition of a patient may help in elucidating an appropriate treatment strategy.

This study aimed to evaluate the accuracy of six threshold-based segmentation methods with different target-to-background ratios (TBR), images with different voxel sizes and image noise, in measuring metabolic volume (MV) and total glycolysis (TG). A standard body phantom consisting of six spheres (inner diameters of 37, 28, 22, 17, 13, and 10 mm) was filled with 18F-FDG solution. The background radioactivity level was 2.65 kBq/mL, and the TBRs were 4 and 8. PET data were acquired for 30 min with list mode. PET data for 30 and 3 min were reconstructed with a three-dimensional ordered subset expectation maximization algorithm plus time-of-flight information with images with 2 and 4 mm isotropic voxels. The six methods examined were absolute standardized uptake value (SUV) of 2.5 (SUV2.5), 41%, 50%, adaptive 41%, and adaptive 50% thresholds of maximum SUV (Th41, Th50, ThA41, and ThA50, respectively); and the contrast-oriented algorithm (ThCOA). Segmented MV and TG were compared with the actual inner volume and expressed as percentages (%MVseg and %TGseg, respectively). In addition, the segmented MV was converted to the diameter, and the differences of it from the reference diameter were compared among six methods. The ThCOA method yielded the most accurate measurements of %MVseg and %TGseg; the difference between %MVseg or %TGseg and its reference were smaller than 10% in 30-min and 15% in 3-min images, but the segmented contour was almost the same as the reference diameter. Measurements with Th50 and ThCOA were highly accurate for both %MVseg and %TGseg in the large spheres, and the adaptive threshold methods, including ThA41, ThA50, and ThCOA, were also highly accurate in the small spheres. The voxel sizes affected the accuracy of %MVseg and %TGseg with a TBR of 4 in any threshold-based methods. Of the six threshold-based segmentation methods studied, ThCOA was the most accurate method for evaluating MV and TG and had only minor dependence on TBRs and sphere size. The small voxel sizes improved the variation of the accuracy in low TBR.

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004–1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042–1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943–0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan–Meier curve (67.1 vs 21.2 vs 65.3, P

The aim of this multicenter prospective study was to compare the sensitivity ofThe study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed byA total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study's analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1-58.2%) was significantly higher than that forFDG-PET/CT showed a superior sensitivity to

A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.

Our objective was to investigate the differences in texture features between step-and-shoot (SS) and continuous-bed-motion (CBM) imaging in phantom and clinical studies.

The ectopic pancreas is often observed in the gastrointestinal tract, and is typically asymptomatic. A 28-year-old woman was referred to our hospital following repeated vomiting after every meal. Following gastroscopy, contrast-enhanced computed tomography (CE-CT), and endoscopic ultrasonography (EUS), she was diagnosed with gastric outlet obstruction, also known as pyloric obstruction, caused by a giant submucosal cystic tumor. The condition was successfully treated with EUS-guided cystic drainage, and she was diagnosed with a cystic tumor originating from the ectopic pancreas. The tumor shrank following EUS-guided cystic drainage, and her obstructive symptoms resolved. In cases with overgrowth of the ectopic pancreas, the differential diagnosis of malignancy is important but challenging. Herein, we report a unique final pathology of this rare case and discuss the findings with a literature review.

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2018 in Japan. It was based on the responses to questionnaires sent to nuclear medicine institutions. Replies were obtained from 999 institutions among 1,230 to which the questionnaire had been sent. Fourteen cases of adverse reactions were reported. A total of 1,017,702 radiopharmaceutical administrations were reported. The incidence of adverse reactions per 100,000 cases was 1.4. No case of deficient products was reported.

This study aimed to compare the qualities of whole-body positron emission tomography (PET) images acquired by the step-and-shoot (SS) and continuous bed motion (CBM) techniques with approximately the same acquisition duration, through phantom and clinical studies. A body phantom with 10–37 mm spheres was filled with 18F-fluorodeoxyglucose (FDG) solution at a sphere-to-background radioactivity ratio of 4:1 and acquired by both techniques. Reconstructed images were evaluated by visual assessment, percentages of contrast (%Q H) and background variability (%N) in accordance with the Japanese guideline for oncology FDG-PET/computed tomography (CT). To evaluate the variability of the standardized uptake value (SUV), the coefficient of variation (CV) for both maximum SUV and peak SUV was examined. Both the SUV values were additionally compared with those of standard images acquired for 30 min, and their accuracy was evaluated by the %difference (%Diff). In the clinical study, whole-body 18F-FDG PET/CT images of 60 patients acquired by both techniques were compared for liver signal-to-noise ratio (SNRliver), CV at end planes, and both SUV values. In the phantom study, the visual assessment and %Q H values of the two techniques did not differ from each other. However, the %N values of the CBM technique were significantly higher than those of the SS technique. Additionally, the CV and %Diff for both SUV values in the CBM images tended to be slightly higher than those in SS images. In the clinical study, the SNRliver values of CBM images were significantly lower than those of SS images, although the CV at the end planes in CBM images was significantly lower than those in SS images. In the Bland–Altman analysis for both SUV values, the mean differences were close to 0, and most lesions exhibited SUVs within the limits of agreement. The CBM technique exhibited slightly lesser uniformity in the center plane than the SS technique. Additionally, in the phantom study, the CV and %Diff of SUV values in CBM images tended to be slightly higher than those of SS images. However, since these differences were subtle, they might be negligible in clinical settings.

Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake is quantified using the heart-to-mediastinum ratio (HMR) with an Anger camera. The relationship between HMR determined using D-SPECT with a cadmium–zinc–telluride detector and an Anger camera is not fully understood. Therefore, the present study aimed to define this relationship using images derived from a phantom and from patients. Cross-calibration phantom studies using an Anger camera with a low-energy high-resolution (LEHR) collimator and D-SPECT, and clinical 123I-MIBG studies proceeded in 40 consecutive patients (80 studies). In the phantom study, a conversion coefficient (CC) was defined based on phantom experiments and applied to the Anger camera and the D-SPECT detector. The HMR was calculated using anterior images with the Anger camera and anterior planograms with D-SPECT. First, the HMR from D-SPECT was cross-calibrated to the Anger camera, and then, the HMR from both cameras were converted to the medium-energy general-purpose collimator condition (CC 0.88; ME88 condition). The relationship between HMR and corrected and uncorrected methods was examined. A 123I-MIBG washout rate was calculated using both methods with and without background subtraction. Based on the phantom experiments, the CC of the Anger camera with an LEHR collimator and of D-SPECT using an anterior planogram was 0.55 and 0.63, respectively. The original HMR from the Anger camera and D-SPECT was 1.76 ± 0.42 and 1.86 ± 0.55, respectively (p

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. 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 131I. Each institute returned the reporting form to the subcommittee each time an adverse reaction occurred. 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 131I-iodomethylnorcholesterol (230.1/105 administrations), followed by 131I-HSA (76.3/105 administrations), 131I-sodium iodohippurate (31.2/105 administrations), and 99mTc-DTPA (12.0/105 administrations). Comparison of adverse reactions between before and after 1997 revealed that prevalence dropped from 3.7/105 administrations (95% confidence interval 3.5–4.1) to 1.5/105 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. These results suggest that nuclear medicine staff must be aware of the possibility of adverse reactions from radiopharmaceuticals, despite their rarity.

Silicosis is caused by inhalation of silica dust and is the most common type of pneumoconiosis. The characteristics of silicosis are inflammation of lung tissue and calcified lymphadenopathy of pulmonary hilum, mediastinum and paratrachea. We present a papillary thyroid carcinoma (PTC) case with paratracheal and superior mediastinal calcified lymphadenopathy caused by silicosis. The patient did not exhibit any respiratory symptoms or abnormal chest x-ray findings due to early phase silicosis. The lymph nodes were thought to be metastasis of PTC before surgery. Patient underwent total thyroidectomy with neck and superior mediastinum dissection. Post-surgery pathological examination exhibited coexistence of silica nodules and micrometastasis of PTC in paratracheal lymph nodes, but only silica nodules were observed in superior mediastinum lymph nodes. Patient's occupation was office worker but had worked as a stonemason for several decades prior. This is a first observed case of superior mediastinal lymphadenopathy by silicosis mimicking metastasis of PTC. Benign calcified lymphadenopathy may mimic metastasis of PTC in the evaluation of neck or mediastinal lesions.

The purpose of this study was to evaluate the degree of cytological radiation damage to lymphocytes occurring after I-131 metaiodobenzylguanidine (MIBG) therapy as determined by the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by I-131 in vivo should result in augmentation of the number of cells with micronuclei. We studied 15 patients with pheochromocytoma (14/15) or ganglioneuroma (1/15), who were treated initially with 7.4 GBq of I-131-MIBG. Isolated lymphocytes collected from patients 10 days after the therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. Serial blood samples were obtained periodically only from two patients for 2 years after therapy. Micronucleus number of micronuclei per 500 binucleated cells was scored by visual inspection. As controls, lymphocytes from the same patients before the therapy were also studied. In an in vitro study, lymphocytes from eight normal volunteers were exposed to doses varying from 0.5 to 2 Gy and studied with the same method. The mean number (mean ± SD) of micronuclei after treatment was significantly increased (p

Various techniques are used in image-guided radiotherapy (IGRT). Cone beam computed tomography (CBCT) is widely used in IGRT on linear accelerators. The increased accuracy of IGRT enables reducing planning target volume margins and doses to normal tissues. However, for radiation therapies requiring fractionated irradiation, increased exposure dose attributed to CBCT becomes problematic. We investigated the smallest projection angle required to provide target accuracy for CBCT of lymph nodes located above or below the collarbone in breast cancer patients.

Background:The purpose of this study was to apply an artificial neural network (ANN) in patients with coronary artery disease (CAD) and to characterize its diagnostic ability compared with conventional visual and quantitative methods in myocardial perfusion imaging (MPI).Methods and Results:A total of 106 patients with CAD were studied with MPI, including multiple vessel disease (49%), history of myocardial infarction (27%) and coronary intervention (30%). The ANN detected abnormal areas with a probability of stress defect and ischemia. The consensus diagnosis based on expert interpretation and coronary stenosis was used as the gold standard. The left ventricular ANN value was higher in the stress-defect group than in the no-defect group (0.92±0.11 vs. 0.25±0.32, P

This survey was performed to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2015 in Japan. It was based on the responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 981 institutions among 1,274 to which the questionnaire had been sent. Fifteen cases of adverse reactions were reported. A total of 1,056,828 radiopharmaceutical administrations were reported. The incidence of adverse reactions per 100,000 cases was 1.4. No case of deficient products was reported.

Purpose Artificial neural networks (ANN) might help to diagnose coronary artery disease. This study aimed to determine whether the diagnostic accuracy of an ANN-based diagnostic system and conventional quantitation are comparable. Methods The ANN was trained to classify potentially abnormal areas as true or false based on the nuclear cardiology expert interpretation of 1001 gated stress/rest 99mTc-MIBI images at 12 hospitals. The diagnostic accuracy of the ANN was compared with 364 expert interpretations that served as the gold standard of abnormality for the validation study. Conventional summed stress/rest/difference scores (SSS/SRS/SDS) were calculated and compared with receiver operating characteristics (ROC) analysis. Results The ANN generated a better area under the ROC curves (AUC) than SSS (0.92 vs. 0.82, p 0.80. Conclusion The ANN was diagnostically accurate in various clinical settings, including that of patients with previous myocardial infarction and coronary revascularization. The ANN could help to diagnose coronary artery disease.

This study aimed to compare the qualities of whole-body positron emission tomography (PET) images acquired by the step-and-shoot (SS) and continuous bed motion (CBM) techniques with approximately the same acquisition duration, through phantom and clinical studies.A body phantom with 10-37 mm spheres was filled withIn the phantom study, the visual assessment and %QThe CBM technique exhibited slightly lesser uniformity in the center plane than the SS technique. Additionally, in the phantom study, the CV and %Diff of SUV values in CBM images tended to be slightly higher than those of SS images. However, since these differences were subtle, they might be negligible in clinical settings.

Objectives: Deep-inspiration breath-hold (DIBH) PET/CT with short-time acquisition and respiratory-gated (RG) PET/CT are performed for pulmonary lesions to reduce the respiratory motion artifacts, and to obtain more accurate standardized uptake value (SUV). DIBH PET/CT demonstrates significant advantages in terms of rapid examination, good quality of CT images and low radiation exposure. On the other hand, the image quality of DIBH PET is generally inferior to that of RG PET because of short-time acquisition resulting in poor signal-to-noise ratio. In this study, RG PET has been regarded as a gold standard, and its detectability between DIBH and RG PET studies was compared using each of the most optimal reconstruction parameters. Methods: In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were determined. In the clinical study, 19 cases were examined using each of the most optimal reconstruction parameters. Results: In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were different. Reconstruction parameters of DIBH PET could be obtained by reducing the number of subsets for those of RG PET in the state of fixing the number of iterations. In the clinical study, high correlation in the maximum SUV was observed between DIBH and RG PET studies. The clinical result was consistent with that of the phantom study surrounded by air since most of the lesions were located in the low pulmonary radioactivity. Conclusion: DIBH PET/CT may be the most practical method which can be the first choice to reduce respiratory motion artifacts if the detectability of DIBH PET is equivalent with that of RG PET. Although DIBH PET may have limitations in suboptimal signal-to-noise ratio, most of the lesions surrounded by low background radioactivity could provide nearly equivalent image quality between DIBH and RG PET studies when each of the most optimal reconstruction parameters was used. © 2013 The Author(s)., In Press / 発行後1年より全文を公開

Summary The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of 111Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2013 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 997 institutions among 1,249 to which the questionnaire had been sent. Eight cases of adverse reactions were reported. A total of 1,056,876 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 0.8. One case of defect products was reported, and the incidence of defect products per 100,000 cases was 0.1.

Background Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is an important method for detecting tumours, planning radiotherapy treatment, and evaluating treatment responses. However, using the standardized uptake value (SUV) threshold with PET imaging may be suitable not to determine gross tumour volume but to determine biological target volume (BTV). The aim of this study was to extract internal target volume of BTV from PET images. Methods Three spherical densities of 18F-FDG were employed in a phantom with an air or water background with repetitive motion amplitudes of 0–30 mm. The PET data were reconstructed with attenuation correction (AC) based on CT images obtained by slow CT scanning (SCS) or helical CT scanning (HCS). The errors in measured SUVmax and volumes calculated using SUV threshold values based on SUVmax (THmax) in experiments performed with varying extents of respiratory motion and AC were analysed. Results A partial volume effect (PVE) was not observed in spheres with diameters of ≥ 28 mm. When calculating SUVmax and THmax, using SCS for AC yielded smaller variance than using HCS (p

Introduction Angiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF 121 , which displays high binding affinity for KDR, and VEGF 165 , which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model. Methods VEGF 121 and VEGF 165 were labeled with 125 I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with 125 I-VEGF 121 . Results 125 I-VEGF 121 and 125 I-VEGF 165 exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. 125 I-VEGF 121 uptake in tumors was twofold higher than that of 125 I-VEGF 165 (9.12±98 and 4.79±1.08 %ID/g at 2 h, respectively). 125 I-VEGF 121 displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with 125 I-VEGF 165 . 125 I-VEGF 121 accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in 125 I-VEGF 121 tumor accumulation correlated with degree of tumor vascularity. Conclusion Radioiodinated VEGF 121 is a promising tracer for noninvasive delineation of angiogenesis in vivo.

Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy.Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy.In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node.This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.

We investigated the feasibility and validity of the sentinel lymph node concept for patients with prostate cancer.A total of 24 patients (mean age 68.1 years) with prostate cancer but without detectable distant metastases were enrolled in this study. Radioactive tracer (technetium labeled phytate) was injected into the prostate 5 to 6 hours before surgery. Preoperative lymphoscintigraphy was viewed, and in vivo and ex vivo gamma probing was performed during the surgery, which included backup extended lymph node dissection. Radioactivity of the excised lymph nodes was measured and validated with an autowell scintillation counter.Radioactive positive (hot) nodes were identified in 17 of the 24 (70.8%) patients by lymphoscintigraphy, in 21 of 24 (87.5%) patients by in vivo probing and in 23 of 24 (95.8%) patients by ex vivo probing. On an individual basis the numbers of hot nodes identified by lymphoscintigraphy and in vivo probing were low (40% and 36%, respectively) compared to the high detection rate for ex vivo probing (91%).Although sentinel lymph nodes can be used for prostate cancer, detailed lymph node mapping and extended dissection backup are currently needed. It is also important to establish novel procedures for accurate and complete removal of all hot nodes.

This study was performed to clarify factors that might influence short-term side effects occurring within 96 hours after administration of 131I for patients with thyroid carcinoma.In 71 patients with differentiated thyroid carcinoma, short-term side effects including gastrointestinal complaints, salivary gland swelling with pain, change in taste and headache were retrospectively analyzed. All patients were given domperidone for prevention of gastrointestinal complaints and advised to consume sour foods to promote discharge of radioiodine from the salivary glands. Selected factors possibly affecting the incidence of side effects were dose per body weight, TSH, effective half-life of 131I, sex, age, 131I accumulation into the stomach and salivary glands, and edema prior to radioiodine administration. The factors were evaluated by multivariate analyses.Incidence of gastrointestinal complaints, salivary gland swelling with pain, change in taste and headache was 65.2%, 50.0%, 9.8% and 4.4%, respectively. In gastrointestinal complaints, the incidence of appetite loss, nausea and vomiting was 60.9%, 40.2% and 7.6%, respectively. The gastrointestinal complaints increased significantly in the patients dosed above 55.5 MBq/kg and with TSH elevation. For salivary gland swelling with pain, female patients displayed a significantly higher incidence than males. No statistically significant factors were detected for change in taste or headache.Significant factors influencing short-term side effects were dose per body weight and TSH values for gastrointestinal complaints, and female sex for salivary gland swelling with pain. Our preliminary experience suggests that the most frequent gastrointestinal complaints can be prevented with ramosetron.

Background Previous reports have demonstrated the feasibility of scintigraphic assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding cassette (ABC) transporters by using 9 9 m Tc cationic tracers such as 9 9 m Tc tetrofosmin (TF). Furthermore, the potential of these tracers for evaluating the effects of reversal agents for MDR has been documented. However, most reversal agents simultaneously affect cationic ion transporters related to tracer accumulation in tumours. Methods The uptake of 9 9 m Tc-TF was examined in the MCF7/WT cell line, a wild-type breast cancer cell line that does not exhibit MDR, and its subclonal etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one of the multi-drug resistance associated proteins (MRPs), in the presence of increasing concentrations of verapamil, a classical MDR modulator. In the absence of verapamil, MCF7/VP cells showed significantly lower 9 9 m Tc-TF uptake than did MCF7/WT cells, indicating that 9 9 m Tc-TF is a substrate for MRP1. The presence of verapamil enhanced the uptake of 9 9 m Tc-TF in MCF7/VP cells. On the other hand, verapamil also increased tracer uptake in MCF7/WT cells, which was readily appreciated when the uptake values were corrected by viable cell numbers: an approximately 100% increase of 9 9 m Tc-TF uptake was observed in comparison with that in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention of radioactivity in both MCF7/WT cells and MCF7/VP cells. Conclusion These results suggest that cellular functions other than MRP1 function, probably cationic ion transporters, are simultaneously and significantly involved in the verapamil induced changes of cellular uptake of 9 9 m Tc-TF. 9 9 m Tc-TF scintigraphy may overestimate the reversal effects of modulators on chemoresistance caused by MRP1 when the modulators simultaneously affect ion transporters.

Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 6 7 Ga in the form of a 6 7 Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 6 7 Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO 2 or 95% N 2 /5% CO 2 for 1 h at 37°C. Cellular uptake of 6 7 Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 6 7 Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 6 7 Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 6 7 Ga citrate in N 2 gas in comparison to that in air (P

医薬保健研究域医学系, Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radio-immunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131 I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131 I-A7 and i.p. administered irrelevant 131 I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n=11), mice undergoing i.p. RIT with 131 I-A7 (n=11), mice undergoing i.v. RIT with 131 I-A7 (n=11) and mice undergoing non-specific i.p. RIT with 131 I-HPMS-1 (n=5). Intraperitoneal injection of 131 I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2±16.5% of the injected dose per g (% ID/ g) and 11.1±3.6% ID/g at 2 h, respectively (P

Background: The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer. Methods: Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 µCi. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography. Results: Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1. Conclusion: These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors.

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml x 100 g(-1) x min(-1) with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.

We report a rare case of double cancers with myocardial metastasis presenting acute myocardial infarction (AMI)-like findings both on an electrocardiogram (ECG) and on Tc-99m-MIBI myocardial SPECT. The ECG showed abnormal Q-waves and ST-segment elecvation in leads V1−V4, and Tc-99m-MIBI SPECT showed a photon deficient area in the anteroseptum. These findings were suggestive of AMI, but the patient had been simultaneously suffering from two adenocarcinomas, which were lung cancer and gastric cancer, and consecutive ultrasonic cardiography (UCG) demonstrated a growing mass lesion in the septal aspect of the left ventricle. After a month he died of severe heart failure. The histological diagnosis of a specimen of the cardiac mass lesion was invasive adenocarcinoma infiltrating to the heart, which revealed that the myocardial metastasis had mimicked AMI. This case shows that it is difficult to distinguish between myocardial infarction and myocardial metastasis with myocardial perfusion SPECT. It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents AMI-like findings.