Occupational radiation exposure among medical personnel in university and general hospitals in Japan.

OBJECTIVE: This study aimed to compare the occupational radiation exposure of medical workers between general hospitals and university hospitals. METHODS: Radiation exposure data from three hospitals in Hiroshima city, including one university hospital and two general hospitals, were collected using personal dosimeters. Monthly radiation doses were analyzed, and the annual sum of radiation exposure dose was calculated for 538 subjects in general hospitals and 1224 subjects in the university hospital. To assess the impact of locality, additional data from Nagasaki University Hospital and Fukushima Medical University Hospital were included for comparative analysis. Professional affiliations, such as doctors, nurses, and radiological technologists, were considered in the evaluation. RESULTS: The study revealed slight but significant differences in radiation doses between general and university hospitals. In general hospitals, except for radiological technologists, a slightly higher radiation dose was observed compared to university hospitals. Despite the annual increase in the use of medical radiation, the majority of hospital workers in both settings adhered to safety guidelines, with occupational radiation exposure remaining below the limit of detection (LOD). Workers who involved in fluoroscopic procedure, whether at university or general hospitals, had higher radiation doses than those who did not. CONCLUSION: The study's primary conclusion is that workers in general hospitals experience a slight but significantly higher radiation dose and a lower percentage below the LOD compared to university hospitals. The observed difference is attributed to the greater workload at general hospitals than at university hospitals, and also may be due to the different nature of university hospital and general hospital. University hospitals, characterized by greater academic orientation, tend to benefit from comprehensive support systems, specialized expertise, and advanced technology, leading to more structured and regulated radiation control. These findings provide a basis for targeted interventions, improved safety protocols.

Radiation Exposure Characteristics among Healthcare Workers: Before and After Japan's Ordinance Revision.

ABSTRACT: Radioactive materials and ionizing radiation have both medical value and disease risks, necessitating radiation dose measurement and risk reduction strategies. The International Commission on Radiological Protection (ICRP) lowered the lens of the eye exposure limit, leading to Japan's revised "Ionizing Radiation Ordinance." However, the effects on radiation exposure in medical settings and compliance feasibility remain unclear. To examine the impact of the revision to the "Ionizing Radiation Ordinance" and use it for measures to reduce exposure to radiation, a comprehensive analysis was conducted on data collected from Nagasaki University Hospital, Hiroshima University Hospital, and Fukushima Medical University Hospital in 2018, 2020, and April to September 2021. This included information on age, sex, occupation, department, and monthly radiation doses of workers, aiming to assess the impact of the revision to the "Ionizing Radiation Ordinance" on radiation exposure before and after its enforcement. Out of 9,076 cases studied, 7,963 (87.7%) had radiation doses below the measurable limit throughout the year. Only 292 cases (3.2%) exceeded 1 mSv y -1 , with 9 doctors and 2 radiological technologists surpassing 5 mSv y -1 . Radiological technologists showed significantly higher doses compared to doctors, dentists, and nurses (p < 0.01), while male subjects had significantly higher exposure doses than females (p < 0.01). No significant changes in radiation exposure were observed before and after the revision of the Ionizing Radiation Ordinance; however, variations in radiation exposure control were noted, particularly among nurses and radiological technologists, suggesting the impact of the revision and the need for tailored countermeasures to reduce radiation dose in each group.

Construction of a Phantom for Image Quality Evaluation in PET/MRI System.

Background: There is no phantom for image quality test in magnetic resonance imaging combined with positron emission tomography systems (PET/MRI systems). In MRI, radioactive water phantom containing 2-deoxy-2-[F-18] fluoro-D-glucose (18F-FDG) cannot be used due to the dielectric effect. Even for phantoms filled with MR-available solutions, the source current of the RF coil is strongly disturbed as the diameter of the phantom increases. Stable MR images require proper phantom size and solution selection. Previous reports have not provided these details. Other than that, few existing phantoms evaluate negative signals such as N-13 ammonia (13N-NH3). We created a phantom for PET/MRI system for image quality test. Methods: The phantom for the PET/MRI system was assembled in two portions. One portion is a signal part containing 18F-FDG radioactive water. The other portion is filled with polyvinyl alcohol glue to construct MRI image to generate µ-map. The glue part is allowed to rewrite the table position overlaps with the first layer, and attenuation correction is performed. Signals are set as positive (4 times and twice higher than background radioactivity) and negative (no radioactivity) columns with different sizes (15 mm φ and 7 mm φ). The PET images with X-ray computed tomography-based attenuation correction (CT-AC) and MRI-AC were evaluated by %-contrasts, variation and uniformity. Results: The %-contrasts of the positive shallow signals with PET/magnetic resonance (MR) and PET/CT were 41.8% and 45.4%, respectively. And it of the positive deep signals with PET/MR and PET/CT were 40.7% and 44.9%. On the other hand, the %-contrasts of the negative shallow signals with PET/MR and PET/CT were 62.3% and 65.6%, respectively. And it of the negative deep signals with PET/MR and PET/CT were 60.7% and 63.7%. Moreover, the % Nj index of uniformity was 2.0% on PET/MRI images and 0.34% on PET/CT images. For negative signals that assume a decrease in myocardial blood flow, The image quality of MR-AC was almost the same as that of CT-AC. Consistency between the images after CT-AC and MR-AC correction were confirmed, and in particular, a stable MR-AC µ-map was obtained in the phantom study. Conclusion: The suggested prototype phantom for generating µ-map is reasonable and useful for evaluating PET/MRI image quality, based on the present standard.

Monitoring of Current Cancer Therapy by Positron Emission Tomography and Possible Role of Radiomics Assessment.

Evaluation of cancer therapy with imaging is crucial as a surrogate marker of effectiveness and survival. The unique response patterns to therapy with immune-checkpoint inhibitors have facilitated the revision of response evaluation criteria using FDG-PET, because the immune response recalls reactive cells such as activated T-cells and macrophages, which show increased glucose metabolism and apparent progression on morphological imaging. Cellular metabolism and function are critical determinants of the viability of active cells in the tumor microenvironment, which would be novel targets of therapies, such as tumor immunity, metabolism, and genetic mutation. Considering tumor heterogeneity and variation in therapy response specific to the mechanisms of therapy, appropriate response evaluation is required. Radiomics approaches, which combine objective image features with a machine learning algorithm as well as pathologic and genetic data, have remarkably progressed over the past decade, and PET radiomics has increased quality and reliability based on the prosperous publications and standardization initiatives. PET and multimodal imaging will play a definitive role in personalized therapeutic strategies by the precise monitoring in future cancer therapy.

Determination of brain tumor recurrence using 11 C-methionine positron emission tomography after radiotherapy.

We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.

Clinicopathologic Significance of False-Positive Lymph Node Status on FDG-PET in Lung Cancer.

INTRODUCTION: 2-[18F] Fluoro-d-deoxyglucose (FDG) positron emission tomography (PET) is a relevant diagnostic procedure for staging lung cancer. However, accurate evaluation of lymph node metastases by PET is controversial because of false-positive FDG uptake. PATIENTS AND METHODS: A total of 245 patients with lung cancer were retrospectively analyzed. Standardized maximum uptake values (SUVmax) of the primary tumor and lymph nodes were compared to pathologic lymph node metastases to correlate PET findings with clinicopathologic variables and patient outcomes. RESULTS: The SUVmax values of metastatic lymph nodes were significantly higher than those of lymph nodes without metastases (P = .0036). When SUVmax ≥ 4 was defined as PET positive for metastasis, the sensitivity, specificity, and accuracy were 48.1%, 79.8%, and 73.1%, respectively. Multivariate logistic regression analysis showed that age > 75 years, bilateral hilar FDG uptake, and no lymph node swelling were significant factors related to false-positive lymph node metastases. Smoking status, FDG uptake in the primary tumor, and concurrent lung diseases were not significant factors. CONCLUSION: Metastatic lymph nodes show higher FDG uptake than false-positive lymph nodes, and older patient age, bilateral hilar FDG uptake, and no swollen nodes are associated with no metastases. Patients with lymph node metastases have worse survival than those with false-positive FDG-PET findings. However, abnormal FDG uptake in the lymph node is an important prognostic factor.

Prognostic impact of preoperative FDG-PET positive lymph nodes in lung cancer.

BACKGROUND: 2-[18F] Fluoro-D-deoxyglucose positron emission tomography (FDG-PET) is an appropriate diagnostic procedure for staging lung cancer. However, accurate evaluation of lymph node (LN) metastases by PET is controversial owing to false-positive/-negative FDG uptake results. The prognostic significance of both false-negative and false-positive LNs on FDG-PET remains to be determined. METHODS: A total of 235 patients with lung cancer were retrospectively analyzed. Maximum standardized uptake values (SUVmax) of the lymph nodes were compared with pathological LN metastases to correlate PET findings with clinicopathological variables and patients' outcomes. RESULTS: When SUVmax ≥ 4 was defined as PET-positive for LN metastasis, sensitivity, specificity, and accuracy were 46.0%, 79.5%, and 72.3%, respectively. False-negative cases and pathological n0 cases were significantly younger, had primary tumors that were smaller or lower SUVmax, and adenocarcinomas compared with false-positive and pathological n+ cases. The difference in survival time between patients with abnormal FDG uptake in the LN and those without was larger than that between pathological LN metastases and no pathological metastases in patients with adenocarcinoma. Multivariate analysis by the Cox proportional hazard model identified smoker, EGFR/ALK negative and LN positive on PET as significant adverse prognostic factors, rather than pathological n-stage. CONCLUSIONS: Abnormal FDG uptake in the LN is an important prognostic factor. Increased glucose metabolism on FDG-PET appears to be a more efficient postoperative prognostic marker than pathological n-stage in patients with lung cancer.

Positron Emission Tomography for Response Evaluation in Microenvironment-Targeted Anti-Cancer Therapy.

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

Human dosimetry of free 211At and meta-[211At]astatobenzylguanidine (211At-MABG) estimated using preclinical biodistribution from normal mice.

BACKGROUND: 211At is one of the ideal nuclides for targeted radionuclide therapies (TRTs). Meta-[211At]astatobenzylguanidine (211At-MABG) has been proposed for the treatment of pheochromocytoma. To effectively use these radiopharmaceuticals, dosimetry must be performed. It is important to determine the absorbed doses of free 211At and 211At-MABG to determine the organs that may be at risk when using TRTs. The aim of this study was to estimate human dosimetry from preclinical biodistribution of free 211At and 211At-MABG in various organs in normal mice. METHODS: Male C57BL/6 N mice were administered 0.13 MBq of free 211At or 0.20 MBq of 211At-MABG by tail-vein injection. The mice were sacrificed at 5 min, and at 1, 3, 6, and 24 h after the injection (n = 5 for each group). The percentage of injected activity per mass in organs and blood (%IA/g) was determined. The human absorbed doses of free 211At and 211At-MABG were calculated using the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) version 2.0 and IDAC-Dose 2.1. RESULTS: High uptake of free 211At was observed in the lungs, spleen, salivary glands, stomach, and thyroid. The absorbed doses of free 211At in the thyroid and several tissues were higher than those of 211At-MABG. The absorbed doses of 211At-MABG in the adrenal glands, heart wall, and liver were higher than those of free 211At. CONCLUSIONS: The absorbed doses of 211At-MABG in organs expressing the norepinephrine transporter were higher than those of free 211At. In addition, the biodistribution of free 211At was different from that of 211At-MABG. The absorbed dose of free 211At may help predict the organs potentially at risk during TRTs using 211At-MABG due to deastatination.

[The Nationwide Survey on Avoidance of Targeted Radionuclide Therapy in Patients with Limited Activities of Daily Living and Those Undergoing Hemodialysis].

Targeted radionuclide therapy with high-dose radioisotopes should be performed in isolation rooms. Patients can be released only after radioactivity remaining in their bodies becomes less than the limits determined by the release criteria in order to secure public protection. Patients are asked to stay in isolation rooms for a few days. Physicians often face difficulties to carry out therapy in patients with limited activities of daily living and those undergoing hemodialysis, and have to avoid therapy in such cases. The Japanese Society of Nuclear Medicine conducted a nationwide survey in order to find out the actual situation. The survey results should reflect future improvement of therapeutic environment in collaborating with related societies and administrative bodies.

Possibility of cancer-stem-cell-targeted radioimmunotherapy for acute myelogenous leukemia using 211At-CXCR4 monoclonal antibody.

To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the 211At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (211At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of 211At-CXCR4 mAb in blood was 15.0 h. The highest tumor uptake of 5.05%ID/g with the highest tumor-to-muscle ratio of 8.51 ± 6.14 was obtained at 6 h. Radiation dosimetry estimated with a human phantom showed absorbed doses of 0.512 mGy/MBq in the bone marrow, 0.287 mGy/MBq in the kidney, and <1 mGy/MBq in other major organs except bone. Sphere model analysis revealed 22.8 mGy/MBq in a tumor of 10 g; in this case, the tumor-to-bone marrow and tumor-to-kidney ratios were 44.5 and 79.4, respectively. The stem-cell-targeted α-particle therapy using 211At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.

Feasibility of gamma camera-based GFR measurement using renal depth evaluated by lateral scan of 99mTc-DTPA renography.

OBJECTIVE: Gamma camera-based measurement of glomerular filtration rate (GFR) with 99mTc-diethylenetriaminepentaacetic acid (DTPA) is an established non-invasive measurement of split renal function; however, it is not as accurate as the plasma sample method. Therefore, study into improving the accuracy of such method is clinically relevant. The aim of this study was to elucidate the feasibility of gamma camera-based GFR measurement using renal depth evaluated by lateral scan of 99mTc-DTPA renography and comparing the results with those of GFR using renal depth measured by CT, and three representative formulas. METHODS: The study population comprised 38 patients (median, 69 years; male 28, female 10; median estimated GFR, 67.4 ml/min) with renourinary disorders. Scintigraphy was performed after intravenous injection of 370 MBq 99mTc-DTPA by dynamic data acquisition for 20 min, followed by a bilateral static scan of the abdomen for 3 min. All patients underwent computed tomography (CT) within 2 months from renography. GFR was calculated by renography using renal depth determined in five ways; lateral scan of 99mTc-DTPA, CT, and three formulas previously created with using weight, height and age. GFRs were compared with estimated GFR (eGFR). The depth of both kidneys measured as described above was compared and evaluated the laterality of the renal depth. RESULTS: The median values of GFR calculated with renal depth determined by 99mTc-DTPA renography, CT, and the three formulas were 87.3, 83.9, 67.8, 68.3, and 71.5 ml/min, respectively. All of them correlated significantly with eGFR (r = 0.734, r = 0.687, r = 0.728, r = 0.726, and r = 0.686, respectively), however, no significant difference was observed among five correlation coefficients. Bland-Altman plot revealed that eGFR had error and fixed bias when compared with GFRs calculated using renal depth determined by renography, CT, and Taylor's formula. The depth of both kidneys measured by 99mTc-DTPA renography was equivalent to that measured by CT, however, those measured by the three formulas were significantly smaller than that measured by 99mTc-DTPA renography. The depth of the right kidney was larger than that of the left kidney using all three formulas in all patients. However, CT detected only 66% of patients to have a deeper right kidney than left kidney. CONCLUSION: Lateral scanning is a feasible procedure to measure renal depth for accurate and reasonable split GFR measurements using 99mTc-DTPA renography.

Determination of the Kinetic Parameters for 123I Uptake by the Thyroid, Thyroid Weights, and Thyroid Volumes in Present-day Healthy Japanese Volunteers.

The purpose of this study was to evaluate the kinetic parameters that determine the uptake rate of radioiodide in the thyroid over 24 h after administration and to estimate thyroid volumes/masses of present-day Japanese. Methods: We determined the thyroid uptake rate of I in healthy male Japanese after oral administration (4.5-8.0 MBq) without iodine restriction. Masses of thyroid glands were collected in 2012-2016 during autopsies of 7,651 male and 3,331 female subjects. Volumes of thyroid glands were estimated by ultrasonography and magnetic resonance imaging in 52 male subjects. Results: The thyroid uptake rate of I for 24 h was 16.1 ± 5.4%. Kinetic model analysis was conducted to obtain the clearances (L h) for thyroid uptake and urinary excretion of I (0.499 ± 0.258 and 2.10 ± 0.39 L h, respectively). The masses of thyroid glands were on average 19.8 g (95% confidence interval of 18.3-19.5 g) and 15.5 g (95% confidence interval of 14.7-16.2 g) in male and female subjects aged 19-52 y, respectively. Volumes of thyroid glands estimated by ultrasonography and magnetic resonance imaging were 17.5 ± 5.2 and 14.2 ± 5.3 mL, respectively. In healthy Japanese, there has been no significant change for at least 50 y in the thyroid uptake of radioiodide over 24 h or in its kinetic parameters. These Japanese-specific kinetic parameters will allow quantitative estimation of the radiation exposure from the Fukushima accident and its variance during the individual's evacuation from or stay in Fukushima.

Time-related study on external exposure dose of 2-deoxy-2-[F-18]fluoro-D-glucose PET for workers' safety.

Time-course study of individual dose equivalents of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (18F-FDG PET) was conducted in different hospital workers, and the daily work duties were analyzed. For the measurements, a semiconductor dosimeter was used. The values at intervals of 1 min and 1 h, the monthly cumulative and daily cumulative doses, and trend graphs were acquired with dedicated software and displayed on the reader. The following radiation workers with duties involving maximum external exposure work were included: doctors making diagnoses (4.8 µSv/procedure), nurses removing injection needles (3.1 µSv/procedure), pharmacists performing quality control tests (2.9 µSv/procedure), nuclear medicine technologists assisting patient positioning (6.5 µSv/procedure), and cyclotron engineers performing daily checks (13.4 µSv/procedure). The results of analysis of daily work duties revealed the influencing factors of external exposure dose. To reduce the external exposure dose, investigators should shorten the patient's contact time with the 18F-FDG source or patient tracer.

Detectability of Malignant Lesions by Whole-Body Magnetic Resonance Imaging Using Whole-Body Integrated Positron Emission Tomography/Magnetic Resonance Imaging.

PURPOSE: To assess the diagnostic ability of whole-body magnetic resonance imaging (MRI) using integrated positron emission tomography/MRI(PET/MRI). METHODS: Axial T2-weighted image (T2WI), diffusion-weighted imaging (DWI), coronal T1-weighted image (T1WI), axial volumetric interpolated breath-hold examination in the lung field, and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET) were evaluated in combination with T2WI alone, T2WI + DWI, T2WI + DWI + T1WI, T2WI + DWI + T1WI + volumetric interpolated breath-hold examination (all MRI images), and all MRI + FDG-PET. RESULTS: A total of 370 lesions were observed in 90 (62.5%) of the 144 patients. The lesion-based sensitivities were 62%, 74%, 74%, 76%, and 94%, and the patient-based sensitivities were 70%, 77%, 77%, 77%, and 81% using T2WI, T2WI + DWI, T2WI + DWI + T1WI, all MRI, and all MRI + FDG-PET, respectively. There were significant differences in the lesion-based sensitivity between T2WI and other sequence combinations and between all MRI and all MRI + FDG-PET. No significant differences were observed between any combinations among the patient-based sensitivities. CONCLUSION: The sensitivity of whole-body MRI was lower when lesion based, but almost equivalent when patient based compared with PET/MRI.

A randomised phase II trial of capecitabine plus cisplatin versus S-1 plus cisplatin as a first-line treatment for advanced gastric cancer: Capecitabine plus cisplatin ascertainment versus S-1 plus cisplatin randomised PII trial (XParTS II).

BACKGROUND: Capecitabine plus cisplatin (XP) is a standard global regimen, while S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP for patients with AGC to confirm whether these regimens can be used as controls in a phase III study and to explore whether histological subtypes favour XP or SP. PATIENTS AND METHODS: Eligible patients were randomised to receive either S-1 40 mg/m2 for 21 days plus cisplatin 60 mg/m2 (q5w) or capecitabine 1000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w). The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), overall response rate (ORR) and safety. RESULTS: In 110 eligible patients, 24-week PFS was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p = 0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most common grade ≥3 adverse events with SP/XP were anaemia (16%/20%), neutropenia (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification showed no statistical difference between treatments. CONCLUSIONS: XP and SP are comparable and can be recommended as control arms in a phase III study for AGC. Histological subtypes were not sensitive markers for the selection of XP or SP. CLINICAL TRIAL REGISTRATION: NCT00140624.