A diagnostic approach of various urethral diseases using multimodal imaging findings: comprehensive overview.

In clinical practice, urethral diseases are not as frequent as conditions affecting other components of the urinary system. Radiological imaging tests, such as retrograde urethrography, CT, MRI, and PET/CT, along with patient history, are crucial for accurately assessing relatively rare urethral lesions. This article aimed to provide a comprehensive overview of urethral lesions, from traumatic changes to neoplasms, and discuss the multimodal imaging findings of various urethral lesions that radiologists should know. To this end, the normal imaging anatomy of the urethra and a step-by-step approach that can be used in clinical practice have been presented to help in the systematic understanding of urethral lesions.

Brain perfusion SPECT in dementia: what radiologists should know.

The findings of brain perfusion single-photon emission computed tomography (SPECT), which detects abnormalities often before changes manifest in morphological imaging, mainly reflect neurodegeneration and contribute to dementia evaluation. A major shift is about to occur in dementia practice to the approach of diagnosing based on biomarkers and treating with disease-modifying drugs. Accordingly, brain perfusion SPECT will be required to serve as a biomarker of neurodegeneration. Hypoperfusion in Alzheimer's disease (AD) is typically seen in the posterior cingulate cortex and precuneus early in the disease, followed by the temporoparietal cortices. On the other hand, atypical presentations of AD such as the posterior variant, logopenic variant, frontal variant, and corticobasal syndrome exhibit hypoperfusion in areas related to symptoms. Additionally, hypoperfusion especially in the precuneus and parietal association cortex can serve as a predictor of progression from mild cognitive impairment to AD. In dementia with Lewy bodies (DLB), the differentiating feature is the presence of hypoperfusion in the occipital lobes in addition to that observed in AD. Hypoperfusion of the occipital lobe is not a remarkable finding, as it is assumed to reflect functional loss due to impairment of the cholinergic and dopaminergic systems rather than degeneration per se. Moreover, the cingulate island sign reflects the degree of AD pathology comorbid in DLB. Frontotemporal dementia is characterized by regional hypoperfusion according to the three clinical types, and the background pathology is diverse. Idiopathic normal pressure hydrocephalus shows apparent hypoperfusion around the Sylvian fissure and corpus callosum and apparent hyperperfusion in high-convexity areas. The cortex or striatum with diffusion restriction on magnetic resonance imaging in prion diseases reflects spongiform degeneration and brain perfusion SPECT reveals hypoperfusion in the same areas. Brain perfusion SPECT findings in dementia should be carefully interpreted considering background pathology.

Advancements in minimal residual disease detection: a practical approach using single-cell droplet PCR for comprehensive monitoring in hematological malignancy.

The identification of chromosomal abnormalities accompanied by copy number alterations is important for understanding tumor characteristics. Testing methodologies for copy number abnormality have limited sensitivity, resulting in their use only for the sample provided at the time of diagnosis or recurrence of malignancy, but not for the monitoring of minimal residual disease (MRD) during and after therapy. We developped the "DimShift" technology which enable to measure the copy number of target gene/chromosome in each cell, which is given by the single cell droplet PCR. Qualitative result of DimShift given by peripheral blood was perfectly concordant with that of bone marrow. These findings and performances are promising to be the new methodology for MRD detection in malignant diseases utilizing bone marrow as well as peripheral blood.

A Novel Method for Acquired Sex Chromosome Mosaicism.

The phenomenon of sex chromosome loss from hematopoietic cells is an emerging indicator of biological aging. While many methods to detect this loss have been developed, enhancing the field, these existing methods often suffer from being labor-intensive, expensive, and not sufficiently sensitive. To bridge this gap, a novel and more efficient technique is developed, named the SinChro assay. This method employs multiplexed single-cell droplet PCR, designed to detect cells with sex chromosome loss at single-cell resolution. Through the SinChro assay, the age-dependent increase in Y chromosome loss in male blood is successfully mapped. The age-dependent loss of the X chromosome in female blood is also identified, a finding that has been challenging with existing methods. The advent of the SinChro assay marks a significant breakthrough in the study of age-related sex mosaicism. Its utility extends beyond blood analysis, applicable to a variety of tissues, and it holds the potential to deepen the understanding of biological aging and related diseases.

[18F]FDG PET/CT Findings of Mass-Forming Actinomycosis in an Uncontrolled Diabetic Patient.

We report a case of cervicofacial actinomycosis mimicking malignant sarcoma in a 78-year-old man with diabetes. High lesion uptake and decreased cerebral uptake on [18F]FDG PET/CT provide a potentially important diagnostic clue suggesting infectious disease in a poorly controlled diabetic patient.

Deep convolutional neural network for differentiating between sarcoidosis and lymphoma based on [18F]FDG maximum-intensity projection images.

OBJECTIVES: To compare the [18F]FDG PET/CT findings of untreated sarcoidosis and malignant lymphoma (ML) and develop convolutional neural network (CNN) models to differentiate between these diseases using maximum intensity projection (MIP) [18F]FDG PET images. METHODS: We retrospectively collected data on consecutive patients newly diagnosed with sarcoidosis and ML who underwent [18F]FDG PET/CT before treatment. Two nuclear radiologists reviewed the images. CNN models were created using MIP PET images and evaluated with k-fold cross-validation. The points of interest were visualized using gradient-weighted class activation mapping (Grad-CAM). RESULTS: A total of 56 patients with sarcoidosis and 62 patients with ML were included. Patients with sarcoidosis had more prominent FDG accumulation in the mediastinal lymph nodes and lung lesions, while those with ML had more prominent accumulation in the cervical lymph nodes (all p < 0.001). For the mediastinal lymph nodes, sarcoidosis patients had significant FDG accumulation in the level 2, 4, 7, and 10 lymph nodes (all p < 0.01). Otherwise, the accumulation in ML patients tended to be in the level 1 lymph nodes (p = 0.08). The CNN model using frontal and lateral MIP images achieved an average accuracy of 0.890 (95% CI: 0.804-0.977), a sensitivity of 0.898 (95% CI: 0.782-1.000), a specificity of 0.907 (95% CI: 0.799-1.000), and an area under the curve of 0.963 (95% CI: 0.899-1.000). Grad-CAM showed that the model focused on the sites of abnormal FDG accumulation. CONCLUSIONS: CNN models based on differences in FDG accumulation sites archive high performance in differentiating between sarcoidosis and ML. CLINICAL RELEVANCE STATEMENT: We developed a CNN model using MIP images of [18F]FDG PET/CT to distinguish between sarcoidosis and malignant lymphoma. It achieved high performance and could be useful in diagnosing diseases with involvement across organs and lymph nodes. KEY POINTS: • There are differences in FDG distribution when comparing whole-body [18F]FDG PET/CT findings in patients with sarcoidosis and malignant lymphoma before treatment. • Convolutional neural networks, a type of deep learning technique, trained with maximum-intensity projection PET images from two angles showed high performance. • A deep learning model that utilizes differences in FDG distribution may be helpful in differentiating between diseases with lesions that are characteristically widespread among organs and lymph nodes.

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients.

OBJECTIVE: 18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer. METHODS: Part A evaluated the pharmacokinetics and exposure doses in three healthy volunteers. Part B evaluated the diagnostic accuracy in patients with untreated preoperative prostate cancer (Cohort 1, n = 7) and patients with biochemical recurrence (Cohort 2, n = 3). All subjects received a single dose of 3.7 MBq/kg 18F-PSMA 1007. Results: 18F-PSMA 1007 was found to be safe and well tolerated in all subjects. No serous AEs or drug-related AEs were identified during the present study. The average blood radioactivity concentration reached a maximum of 47.87 ± 1.05 (percentage of injected dose [%ID]/ml) at 5 min and then decreased to 1.60 ± 0.78 in 6 h. The systemic radioactivity reached a maximum of 211.05 ± 6.77 (%ID$\times$103) at 5 min and decreased to 7.18 ± 3.91 in 6 h. The sensitivity and positive predictive value were 100% and 100% based on both pathologic and imaging confirmation as gold standard. In Cohort 1, 15 primary foci (11.9%) were >5 mm in the largest diameter and identified in 39 of 126 segments (30.1%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 60 min uptake time acquisition were 80.0, 96.5, 91.4, 91.2 and 91.3%, respectively. CONCLUSIONS: Our study revealed that 18F-PSMA 1007 was safe, well tolerated and showed high accuracy in the diagnosis of prostate cancer.

Correlation between choline kinase alpha expression and 11C-choline accumulation in breast cancer using positron emission tomography/computed tomography: a retrospective study.

Choline kinase (CK) is reportedly overexpressed in various malignancies. Among its isoforms, CKα overexpression is presumably related to oncogenic change. Choline positron emission tomography (PET) is reportedly useful for detecting and evaluating therapy outcomes in malignancies. In this study, we investigated the correlation between CKα expression and 11C-choline accumulation in breast cancer cells. We also compared the CKα expression level with other pathological findings for investigating tumour activity. Fifty-six patients with breast cancer (mean age: 51 years) who underwent their first medical examination between May 2007 and December 2008 were enrolled. All the patients underwent 11C-choline PET/computed tomography imaging prior to surgery. The maximum standardised uptake value was recorded for evaluating 11C-choline accumulation. The intensity of CKα expression was classified using immunostaining. A significant correlation was observed between CKα expression and 11C-choline accumulation (P < 0.0001). A comparison of breast cancer mortality demonstrated that strong CKα expression was associated with a shorter survival time (P < 0.0001). 11C-choline accumulation was also negatively correlated with survival time (P < 0.0001). Tumours with strong CKα expression are reportedly highly active in breast cancer. A correlation was observed between CKα expression and 11C-choline accumulation, suggesting their role as prognostic indicators of breast cancer.

Novel utility of Vesical Imaging-Reporting and Data System in multimodal treatment for muscle-invasive bladder cancer.

OBJECTIVES: To examine the clinical significance of the Vesical Imaging-Reporting and Data System (VI-RADS) in predicting outcome of multimodal treatment (MMT) in muscle-invasive bladder cancer (MIBC) patients. METHODS: We reviewed 78 pathologically proven MIBC patients who underwent MMT including transurethral resection and chemoradiotherapy, followed by partial or radical cystectomy. Treatment response was assessed through histologic evaluation of cystectomy specimens. Two radiologists categorized the index lesions of pretherapeutic MRI according to the 5-point VI-RADS score. The associations of VI-RADS score with the therapeutic effect of MMT were analyzed. The diagnostic performance of VI-RADS scores with a cut-off VI-RADS scores ≤ 2 or ≤ 3 for predicting pathologic complete response to MMT (MMT-CR) was evaluated. RESULTS: MMT-CR was achieved in 2 (100%) of VI-RADS score 1 (n = 2), 16 (84%) of score 2 (n = 19), 12 (86%) of score 3 (n = 14), 7 (64%) of score 4 (n = 11), and 14 (44%) of score 5 (n = 32). VI-RADS score was inversely associated with the incidence of MMT-CR (p = 0.00049). The cut-off VI-RADS score ≤ 2 and ≤ 3 could predict the favorable therapeutic outcome of MMT with high specificity (0.89 with 95% confidence interval [CI]: 0.71-0.98 and 0.82 with 95% CI: 0.62-0.94, respectively) and high positive predictive value (0.86 with 95% CI: 0.64-0.97 and 0.86 with 95% CI: 0.70-0.95, respectively). CONCLUSION: VI-RADS score may serve as an imaging marker in MIBC patients for predicting the therapeutic outcome of MMT. CLINICAL RELEVANCE STATEMENT: Muscle-invasive bladder cancer patients with a lower Vesical Imaging-Reporting and Data System score can be a good candidate for bladder-sparing treatment incorporating multimodal treatment. KEY POINTS: • Vesical Imaging-Reporting and Data System (VI-RADS) score was potentially valuable for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The likelihood of achieving complete response of multimodal treatment (MMT) decreased with increasing VI-RADS score. • VI-RADS score could serve as an imaging marker that optimizes patient selection for MMT.

Deep Learning-Based Image Quality Improvement in Digital Positron Emission Tomography for Breast Cancer.

We investigated whether 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography images restored via deep learning (DL) improved image quality and affected axillary lymph node (ALN) metastasis diagnosis in patients with breast cancer. Using a five-point scale, two readers compared the image quality of DL-PET and conventional PET (cPET) in 53 consecutive patients from September 2020 to October 2021. Visually analyzed ipsilateral ALNs were rated on a three-point scale. The standard uptake values SUVmax and SUVpeak were calculated for breast cancer regions of interest. For "depiction of primary lesion", reader 2 scored DL-PET significantly higher than cPET. For "noise", "clarity of mammary gland", and "overall image quality", both readers scored DL-PET significantly higher than cPET. The SUVmax and SUVpeak for primary lesions and normal breasts were significantly higher in DL-PET than in cPET (p < 0.001). Considering the ALN metastasis scores 1 and 2 as negative and 3 as positive, the McNemar test revealed no significant difference between cPET and DL-PET scores for either reader (p = 0.250, 0.625). DL-PET improved visual image quality for breast cancer compared with cPET. SUVmax and SUVpeak were significantly higher in DL-PET than in cPET. DL-PET and cPET exhibited comparable diagnostic abilities for ALN metastasis.

Motility Mapping Quantification Using the Classical Optical Flow Algorithm for Small Bowel Crohn's Disease: Comparison with Balloon-assisted Enteroscopy Findings.

PURPOSE: To quantify bowel motility shown on cine MRI using the classical optical flow algorithm and compare it with balloon-assisted enteroscopy (BAE) findings in patients with Crohn's disease (CD). METHODS: This retrospective study included 29 consecutive patients with CD who had undergone MR enterocolonography (MREC) and BAE between March and May 2017. We developed computer software to present motion vector magnitudes between consecutive cine MR images as bowel motility maps via a classical optical flow algorithm using the Horn-Schunck method. Cine MR images were acquired with a balanced steady-state free precession sequence in the coronal direction to capture small bowel motility. The small bowels were divided into three segments. In total, 63 bowel segments were assessed via BAE and MREC. Motility scores on the maps, simplified MR index of activity (sMaRIA), and MREC score derived from a 5-point MR classification were assessed independently by two radiologists and compared with the CD endoscopic index of severity (CDEIS). Correlations were assessed using Spearman's rank coefficient. The areas under the receiver-operating characteristic curve (AUCs) of motility score for differentiating CDEIS was calculated; a P value < 0.05 was considered statistically significant. RESULTS: Motility score was negatively correlated with CDEIS (r = -0.59 [P < 0.001] and -0.54 [P < 0.001]), and the AUCs of motility scores for detecting CDEIS ≥ 3 were 88.2% and 78.6% for observers 1 and 2, respectively. There were no significant differences in the AUC for detecting CDEIS ≥ 3 and CDEIS ≥ 12 between motility and sMaRIA or MREC score. CONCLUSION: The motility map was feasible for locally quantifying the bowel motility. In addition, the motility score on the map reflected the endoscopic inflammatory activity of each small bowel segment in patients with CD; hence, it could be used as a tool in objectively interpreting cine MREC to predict inflammatory activity in CD.

Enhancement of 18F-Fluorodeoxyglucose PET Image Quality by Deep-Learning-Based Image Reconstruction Using Advanced Intelligent Clear-IQ Engine in Semiconductor-Based PET/CT Scanners.

Deep learning (DL) image quality improvement has been studied for application to 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). It is unclear, however, whether DL can increase the quality of images obtained with semiconductor-based PET/CT scanners. This study aimed to compare the quality of semiconductor-based PET/CT scanner images obtained by DL-based technology and conventional OSEM image with Gaussian postfilter. For DL-based data processing implementation, we used Advanced Intelligent Clear-IQ Engine (AiCE, Canon Medical Systems, Tochigi, Japan) and for OSEM images, Gaussian postfilter of 3 mm FWHM is used. Thirty patients who underwent semiconductor-based PET/CT scanner imaging between May 6, 2021, and May 19, 2021, were enrolled. We compared AiCE images and OSEM images and scored them for delineation, image noise, and overall image quality. We also measured standardized uptake values (SUVs) in tumors and healthy tissues and compared them between AiCE and OSEM. AiCE images scored significantly higher than OSEM images for delineation, image noise, and overall image quality. The Fleiss kappa value for the interobserver agreement was 0.57. Among the 21 SUV measurements in healthy organs, 11 (52.4%) measurements were significantly different between AiCE and OSEM images. More pathological lesions were detected in AiCE images as compared with OSEM images, with AiCE images showing higher SUVs for pathological lesions than OSEM images. AiCE can improve the quality of images acquired with semiconductor-based PET/CT scanners, including the noise level, contrast, and tumor detection capability.

Comparison of 18F-fluorothymidine Positron Emission Tomography/Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Breast Cancer.

The uptake of 18F-fluorothymidine (18F-FLT) depends on cells' proliferative rates. We compared the characteristics of 18F-FLT positron emission tomography/computed tomography (PET/CT) with those of 18F-fluorodeoxyglucose (18F-FDG) PET/CT for breast cancer. We prospectively diagnosed patients with breast cancer who underwent 18F-FLT PET/CT and 18F-FDG PET/CT. Subsequently, significant differences and correlation coefficients of the maximum standardized uptake value (SUVmax) in primary breast cancer and axillary lymph nodes were statistically evaluated. We enrolled eight patients with breast cancer. In six treatment-naive patients, the SUVmax for primary lesions showed a significant difference (mean, 2.1 vs. 4.1, p = 0.031) and a strong correlation (r = 0.969) between 18F-FLT and 18F-FDG. Further, although the SUVmax for the axillary lymph nodes did not show a significant difference between 18F-FLT and 18F-FDG (P = 0.246), there was a strong correlation between the two (r = 0.999). In a patient-by-patient study, there were cases in which only 18F-FDG uptake was observed in lymph nodes and normal breasts. Bone metastases demonstrated lower accumulation than bone marrow on the 18F-FLT PET/CT. In conclusion, a strong correlation was observed between the 18F-FLT PET/CT and 18F-FDG PET/CT uptake. Differences in the biochemical characteristics of 18F-FLT and 18F-FDG were reflected in the accumulation differences for breast cancer, metastatic lesions, and normal organs.

Branch-like enhancement on contrast enhanced MRI is a specific finding of cerebellar lymphoma compared with other pathologies.

Branch-like enhancement (BLE) on contrast-enhanced (CE) magnetic resonance imaging (MRI) was found to be effective in differentiating primary central nervous system lymphoma (PCNSL) from high-grade glioma (HGG) in the cerebellum. However, whether it can be applied to assessments of secondary central nervous system lymphoma (SCNSL), or other cerebellar lesions is unknown. Hence, we retrospectively reviewed cerebellar masses to investigate the use of BLE in differentiating cerebellar lymphoma (CL), both primary and secondary, from other lesions. Two reviewers qualitatively evaluated the presence and degree of BLE on CE-T1 weighted imaging (T1WI). If multiple views were available, we determined the view in which BLE was the most visible. Seventy-five patients with the following pathologies were identified:17 patients with CL, 30 patients with metastasis, 12 patients with hemangioblastoma, 9 patients with HGG, and 7 patients with others. Twelve patients presented with PCNSL and five with SCNSL. Of 17 patients with CL, 15 (88%) had BLE, whereas three (5%) out of 58 patients in the non-CL group showed BLE. In patients who underwent three-dimensional-CE-T1WI, BLE was the most visible on the sagittal image. In conclusion, BLE is a highly specific finding for CL and the sagittal image is important in evaluating this finding.

A Rare Case of Radiation-Induced Liver Disease in Treated Abdominal Lymphoma Showing High [18F]FDG Avidity and Low EOB Uptake Proportional to the Irradiation Dose.

A 44-year-old woman presented with high [18F]FDG uptake liver lesion after six courses of R-CHOP and radiotherapy for abdominal DLBCL, which was misdiagnosed as a hepatic invasion. EOB-MRI showed slight T2 hyperintensity, low-intensity DWI, and decreased EOB uptake in the hepatocellular phase. Compared with the pretreatment planning CT, the liver lesion coincided with the area of >40.5 Gy, resulting in the diagnosis of RILD. At the follow-up [18F]FDG PET/CT 7 months after irradiation, the abnormal liver uptake disappeared. Comparing [18F]FDG PET/CT, EOB-MRI, and planning CT can lead to the correct diagnosis of RILD and avoid unnecessary biopsies and treatment changes.

Deep Learning Using Multiple Degrees of Maximum-Intensity Projection for PET/CT Image Classification in Breast Cancer.

Deep learning (DL) has become a remarkably powerful tool for image processing recently. However, the usefulness of DL in positron emission tomography (PET)/computed tomography (CT) for breast cancer (BC) has been insufficiently studied. This study investigated whether a DL model using images with multiple degrees of PET maximum-intensity projection (MIP) images contributes to increase diagnostic accuracy for PET/CT image classification in BC. We retrospectively gathered 400 images of 200 BC and 200 non-BC patients for training data. For each image, we obtained PET MIP images with four different degrees (0°, 30°, 60°, 90°) and made two DL models using Xception. One DL model diagnosed BC with only 0-degree MIP and the other used four different degrees. After training phases, our DL models analyzed test data including 50 BC and 50 non-BC patients. Five radiologists interpreted these test data. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Our 4-degree model, 0-degree model, and radiologists had a sensitivity of 96%, 82%, and 80-98% and a specificity of 80%, 88%, and 76-92%, respectively. Our 4-degree model had equal or better diagnostic performance compared with that of the radiologists (AUC = 0.936 and 0.872-0.967, p = 0.036-0.405). A DL model similar to our 4-degree model may lead to help radiologists in their diagnostic work in the future.

Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer.

OBJECTIVES: To examine the usefulness of the texture analysis (TA) of apparent diffusion coefficient (ADC) maps in predicting the chemoradiotherapy (CRT) response of muscle-invasive bladder cancer (MIBC). METHODS: We reviewed 45 MIBC patients who underwent cystectomy after CRT. CRT response was assessed through histologic evaluation of cystectomy specimens. Two radiologists determined the volume of interest for the index lesions on ADC maps of pretherapeutic 1.5-T MRI and performed TA using the LIFEx software. Forty-six texture features (TFs) were selected based on their contribution to the prediction of CRT sensitivity. To evaluate diagnostic performance, diagnostic models from the selected TFs were created using random forest (RF) and support vector machine (SVM), respectively. RESULTS: Twenty-three patients achieved pathologic complete response (pCR) to CRT. The feature selection identified first quartile ADC (Q1 ADC), gray-level co-occurrence matrix (GLCM) correlation, and GLCM homogeneity as important in predicting CRT response. Patients who achieved pCR showed significantly lower Q1 ADC and GLCM correlation values (0.66 × 10-3 mm2/s and 0.53, respectively) than those who did not (0.81 × 10-3 mm2/s and 0.70, respectively; p < 0.05 for both). The AUCs of the RF and SVM models incorporating the selected TFs were 0.82 (95% confidence interval [CI]: 0.67-0.97) and 0.96 (95% CI: 0.91-1.00), respectively, and the AUC of the SVM model was better than that of the mean ADC value (0.76, 95% CI: 0.61-0.90; p = 0.0037). CONCLUSION: TFs can serve as imaging biomarkers in MIBC patients for predicting CRT sensitivity. TAs of ADC maps can potentially optimize patient selection for CRT. KEY POINTS: • Texture analysis of ADC maps and feature selection identified important texture features for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The machine learning model incorporating the texture features set, which included first quartile ADC, GLCM correlation, and GLCM homogeneity, showed high performance in predicting chemoradiotherapy response. • Texture features could serve as imaging biomarkers that optimize eligible patient selection for chemoradiotherapy in muscle-invasive bladder cancer.

Safety and response after peptide receptor radionuclide therapy with 177 Lu-DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial.

BACKGROUND: The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of 177 Lu-DOTATATE (four cycles of 7.4 GBq) in Japanese patients with unresectable, progressive neuroendocrine tumors (NETs). METHODS: From April 2018 to October 2020, 15 patients with advanced NETs (five midgut, eight pancreatic, and two lung NETs) were enrolled. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were evaluated. Pharmacokinetics and dosimetry were also evaluated in three midgut patients. RESULTS: The mean absorbed doses of 177 Lu-DOTATATE to the kidneys (20.7 Gy/29.6 GBq) and the bone marrow (0.631 Gy/29.6 GBq) were within the radiation tolerance doses. The ORR of the whole population was 53% (90% CI, 30%-76%). ORRs of the midgut and non-midgut NETs were 60% (90% CI, 19%-92%) and 50% (90% CI, 22%-78%), respectively. There was no difference in the maximum reduction rate of the sum of the target lesion diameters between patients with midgut and non-midgut NET. The median PFS was not reached; the PFS rate at 52 weeks was 80% (90% CI, 56.1%-91.7%). AEs of Grade 3 or higher were lymphopenia (47%) and leukopenia (7%). CONCLUSION: 177 Lu-DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs.