Publications by authors named "Yuji Nakamoto"

233 Publications

First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas.

Front Endocrinol (Lausanne) 2021 19;12:717101. Epub 2021 Aug 19.

Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Pancreatic β-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic β-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [F]FB(ePEG12)12-exendin-4 (F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. F-Ex4 is promising for clinical PET imaging targeting pancreatic β cells.
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http://dx.doi.org/10.3389/fendo.2021.717101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417326PMC
August 2021

Pediatric abdominal arterial intervention using a steerable microcatheter through an introducer with 4-F outer diameter: report of two cases.

Radiol Case Rep 2021 Nov 27;16(11):3326-3329. Epub 2021 Aug 27.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

In pediatric arteriography, vascular complications are more common than in adults; thus, the use of the smallest catheter to accomplish the objective of the procedure is recommended. We describe two pediatric cases in which abdominal arterial embolization and arteriography were performed with steerable microcatheters without conventional diagnostic catheters. Additionally, we used an introducer with an outer diameter of 4-F in a Mini Access Kit (Merit Medical, South Jordan, UT) as a vascular sheath to reduce sheath size. We believe that this technique may be feasible and safe for abdominal arterial interventions in children.
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http://dx.doi.org/10.1016/j.radcr.2021.07.095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403709PMC
November 2021

Diagnostic Value of DCE-MRI for Differentiating Malignant Adnexal Masses Compared with Contrast-enhanced-T1WI.

Magn Reson Med Sci 2021 Sep 3. Epub 2021 Sep 3.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine.

Purpose: To compare the diagnostic performance of dynamic contrast-enhanced-MR (DCE-MR) and delayed contrast-enhanced (CE)-MRI added to unenhanced MRI, including diffusion weighted image (DWI) for differentiating malignant adnexal tumors, conducting a retrospective blinded image interpretation study.

Methods: Data of 80 patients suspected of having adnexal tumors by ultrasonography between April 2008 and August 2018 were used for the study. All patients had undergone preoperative MRI and surgical resection at our institution. Four radiologists (two specialized in gynecological radiology and two non-specialized) were enrolled for blinded review of the MR images. A 3-point scale was used: 0 = benign, 1 = indeterminate, and 2 = malignant. Three imaging sets were reviewed: Set A, unenhanced MRI including DWI; Set B, Set A and delayed CE-T1WI; and Set C, Set A and DCE-MRI. Imaging criteria for benign and malignant tumors were given in earlier reports. The diagnostic performance of the three imaging sets of the four readers was calculated. Their areas under the curve (AUCs) were compared using the DeLong method.

Results: Accuracies of Set B were 81%-88%. Those of Set C were 81%-85%. The AUCs of Set B were 0.83 and 0.89. Those of Set C were 0.81-0.86. For two readers, Set A showed lower accuracy and AUC than Set B/Set C (less than 0.80), although those were equivalent in other readers. No significant difference in AUCs was found among the three sequence sets. Intrareader agreement was moderate to almost perfect in Sets A and B, and substantial to almost perfect in Set C.

Conclusion: DCE-MR showed no superiority for differentiating malignant adnexal tumors from benign tumors compared to delayed CE-T1WI with conventional MR and DWI.
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http://dx.doi.org/10.2463/mrms.mp.2021-0003DOI Listing
September 2021

Novel Artificial Intelligence-based Technology for Chest Computed Tomography Analysis of Idiopathic Pulmonary Fibrosis.

Ann Am Thorac Soc 2021 Aug 19. Epub 2021 Aug 19.

Kyoto University Graduate School of Medicine, Department of Respiratory Medicine, Kyoto, Japan;

Rationale: There is a growing need to accurately estimate the prognosis of idiopathic pulmonary fibrosis (IPF) in clinical practice, given the development of effective drugs for treating IPF.

Objective: To develop artificial intelligence-based image analysis software to detect parenchymal and airway abnormalities on chest computed tomography (CT) and to explore their prognostic importance in patients with IPF.

Methods: A novel artificial intelligence-based quantitative CT image analysis software (AIQCT) was developed by applying 304 HRCT scans from patients with diffuse lung diseases as the training set. AIQCT automatically categorized and quantified ten types of parenchymal patterns as well as airways, expressing the volumes as percentages of the total lung volume. To validate the software, the area percentages of each lesion quantified by AIQCT were compared with those of the visual scores using 30 plain HRCT images with lung diseases. In addition, three-dimensional analysis for similarity with ground truth was performed using HRCT images from 10 patients with IPF. AIQCT was then applied to 120 patients with IPF who underwent chest HRCT scanning at our institute. Associations between the measured volumes and survival were analyzed.

Results: The correlations between AIQCT and the visual scores were moderate to strong (correlation coefficient 0.44 to 0.95) depending on the parenchymal pattern. The Dice indexes for similarity between AIQCT data and ground truth were 0.67, 0.76, and 0.64 for reticulation, honeycomb, and bronchi, respectively. During a median follow-up period of 2,184 days, 66 patients died, and 1 underwent lung transplantation. In multivariable Cox regression analysis, bronchial volumes [adjusted hazard ratio (HR), 1.33; 95% confidence interval (CI), 1.16 to 1.53] and normal lung volumes (adjusted HR, 0.97; 95% CI, 0.94 to 0.99) were independently associated with survival after adjusting for the GAP stage of IPF.

Conclusions: Our newly developed artificial intelligence-based image analysis software successfully quantified parenchymal lesions and airway volumes. Bronchial and normal lung volumes on chest HRCT may provide additional prognostic information on the GAP stage of IPF.
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http://dx.doi.org/10.1513/AnnalsATS.202101-044OCDOI Listing
August 2021

Diagnostic Accuracy of Magnetic Resonance Imaging for International Federation of Gynecology and Obstetrics 2018 IB to IIB Cervical Cancer Staging: Comparison Among Magnetic Resonance Sequences and Pathologies.

J Comput Assist Tomogr 2021 Aug 16. Epub 2021 Aug 16.

From the Departments of Diagnostic Radiology and Nuclear Medicine Gynecology and Obstetrics, Kyoto University Hospital Department of Radiology, National Hospital Organization Kyoto Medical Center Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.

Objective: This study aimed to investigate the most accurate magnetic resonance (MR) sequence for tumor detection, maximal tumor diameter, and parametrial invasion compared with histopathologic diagnoses.

Methods: Fifty-one patients with International Federation of Gynecology and Obstetrics 2018 IB1 to IIB cervical cancer underwent preoperative MR imaging and surgical resection. Two radiologists independently evaluated the tumor detection, parametrial invasion, and tumor size in each of T2-weighted image, diffusion-weighted image, and contrast-enhanced T1-weighted image. Results obtained for squamous cell carcinoma (SCC) and adenocarcinoma were also compared.

Results: Neither the tumor detection rate nor parametrial invasion was found to be significantly different among sequences. Tumor size assessment using MR imaging with pathology showed good correlation: r = 0.63-0.72. The adenocarcinoma size tended to be more underestimated than SCC in comparison with the pathologic specimen.

Conclusions: Cervical cancer staging by MR images showed no significant difference among T2-weighted image, diffusion-weighted image, and contrast-enhanced T1-weighted image. Adenocarcinoma was prone to be measured as smaller than the pathologic specimen compared with SCC.
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http://dx.doi.org/10.1097/RCT.0000000000001210DOI Listing
August 2021

A Proposed Dedicated Breast PET Lexicon: Standardization of Description and Reporting of Radiotracer Uptake in the Breast.

Diagnostics (Basel) 2021 Jul 15;11(7). Epub 2021 Jul 15.

Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto-City 606-8507, Kyoto, Japan.

Dedicated breast positron emission tomography (dbPET) is a new diagnostic imaging modality recently used in clinical practice for the detection of breast cancer and the assessment of tumor biology. dbPET has higher spatial resolution than that of conventional whole body PET systems, allowing recognition of detailed morphological attributes of radiotracer accumulation within the breast. F-fluorodeoxyglucose (F-FDG) accumulation in the breast may be due to benign or malignant entities, and recent studies suggest that morphology characterization of F-FDG uptake could aid in estimating the probability of malignancy. However, across the world, there are many descriptors of breast F-FDG uptake, limiting comparisons between studies. In this article, we propose a lexicon for breast radiotracer uptake to standardize description and reporting of image findings on dbPET, consisting of terms for image quality, radiotracer fibroglandular uptake, breast lesion uptake.
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http://dx.doi.org/10.3390/diagnostics11071267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306936PMC
July 2021

Quiet Diffusion-weighted MR Imaging of the Brain for Pediatric Patients with Moyamoya Disease.

Magn Reson Med Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine.

Purpose: Diffusion-weighted MRI (DWI) is an essential sequence for evaluating pediatric patients with moyamoya disease (MMD); however, acoustic noise associated with DWI may lead to motion artifact. Compared with conventional DWI (cDWI), quiet DWI (qDWI) is considered less noisy and able to keep children more relaxed and stable. This study aimed to evaluate the suitability of qDWI compared with cDWI for pediatric patients with MMD.

Methods: In this observational study, MR examinations of the brain were performed either with or without sedation in pediatric patients with MMD between September 2017 and August 2018. Three neuroradiologists independently evaluated the images for artifacts and restricted diffusion in the brain. The differences between qDWI and cDWI were compared statistically using a chi-square test.

Results: One-hundred and six MR scans of 56 patients with MMD (38 scans of 15 sedated patients: 6 boys and 9 girls; mean age, 5.2 years; range, 1-9 years; and 68 scans of 42 unsedated patients: 19 boys and 23 girls; mean age, 10.7 years; range, 7-16 years) were evaluated. MR examinations were performed either with or without sedation (except in one patient). In sedated patients, no artifact other than susceptibility was observed on qDWI, whereas four artifacts were observed on cDWI (P = .04). One patient awoke from sedation during cDWI scanning, while no patient awoke from sedation during qDWI acquisition. For unsedated patients, three scans showed artifacts on qDWI, whereas two scans showed artifacts on cDWI (P = .65). Regarding restricted diffusion, qDWI revealed three cases, while two cases were found on cDWI (P = .66).

Conclusion: qDWI induced fewer artifacts compared with cDWI in sedated patients, and similar frequencies of artifacts were induced by qDWI and by cDWI in unsedated patients. qDWI showed restricted diffusion comparable to cDWI.
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http://dx.doi.org/10.2463/mrms.mp.2020-0174DOI Listing
July 2021

Intranodal Lymphangiography during Surgical Repair of Pelvic Lymphorrhea after Radical Cystectomy.

Case Rep Urol 2021 5;2021:7822422. Epub 2021 Jul 5.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Japan.

Lymphorrhea can develop after various types of surgeries. Surgical closure of the lymphatic leakage point is an effective treatment option. However, it is difficult to identify the leakage point sometimes. Here, we report a case of pelvic lymphorrhea after radical cystectomy for bladder cancer. Identification of the leakage point was difficult during laparoscopic surgical repair of lymphorrhea. Intranodal lymphangiography was performed via the inguinal lymph node by injection of lipiodol, followed by injection of indigo carmine. Laparoscopy revealed extravasation of lipiodol and indigo carmine from the pelvic wall. The leakage point was successfully cauterized using an electric scalpel. Lymphorrhea improved after the surgical repair. This case suggests that intranodal lymphangiography may be useful for detecting the site of lymphatic leakage during the surgical repair of lymphorrhea.
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http://dx.doi.org/10.1155/2021/7822422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277509PMC
July 2021

Distinctive detection of insulinoma using [F]FB(ePEG12)12-exendin-4 PET/CT.

Sci Rep 2021 Jul 22;11(1):15014. Epub 2021 Jul 22.

Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53;Rb mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.
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http://dx.doi.org/10.1038/s41598-021-94595-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298522PMC
July 2021

Identifying Patients Who May Benefit from Liver Resection Compared to Living Donor Liver Transplantation for Hepatocellular Carcinoma Using F-FDG PET.

World J Surg 2021 Jul 17. Epub 2021 Jul 17.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: This study aimed to assess an oncologic setting where patients with hepatocellular carcinoma (HCC) could benefit from liver resection (LR) compared to living donor liver transplantation (LDLT) using F-fluorodeoxyglucose (FDG) positron emission tomography.

Methods: The consecutive data of patients with HCC who underwent F-FDG PET before LR (LR group, n = 314) and LDLT (LDLT group, n = 65) between 2003 and 2015 were retrospectively analyzed. Tumor F-FDG avidity was quantified as the tumor to liver standardized uptake value ratio (TLR, cut-off value was defined at 2). Multivariate analysis was performed to assess significant preoperative tumor factors in the LR group. Survival outcomes between the two groups were stratified by these factors.

Results: The 5-year overall survival (OS: 56.9% vs. 73.8%, LR vs. LDLT, p < 0.001) and recurrence-free survival rate (RFS: 27.4% vs. 70.7%, p < 0.001) were significantly better in the LDLT group compared to the LR group. In the LR study, multivariate analysis identified TLR and tumor multiplicity as significant preoperative tumor factors for OS. In patients with solitary and TLR < 2 HCC, the 5-year OS rate was not significantly different between the LR and LDLT groups (70.3% vs. 71.8%, p = 0.352); meanwhile, RFS rate was better in the LDLT group (34.3% vs. 71.8%, p = 0.001).

Conclusions: LDLT is associated with better long-term outcomes than LR in patients with HCC; however, selected patients with solitary and TLR < 2 HCC may benefit from LR.
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http://dx.doi.org/10.1007/s00268-021-06235-9DOI Listing
July 2021

Two Cases of Epstein-Barr Virus-Positive Mucocutaneous Ulcer Mimicking Head and Neck Cancers in 18F-FDG PET/CT.

Clin Nucl Med 2021 Jul 14. Epub 2021 Jul 14.

From the Departments of Diagnostic Imaging and Nuclear Medicine Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto City, Japan.

Abstract: Epstein-Barr virus-positive mucocutaneous ulcer is a newly recognized clinicopathological entity among mature B-cell neoplasms according to the 2016 revision of the World Health Organization diagnostic criteria. Here, we present FDG PET/CT images of 2 Epstein-Barr virus-positive mucocutaneous ulcer cases. Both cases shown in the images mimicked head and neck cancers, which are similar to carcinomas of the tonsil and gingiva, respectively, and both lesions showed intense FDG uptake on PET scan.
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http://dx.doi.org/10.1097/RLU.0000000000003807DOI Listing
July 2021

Correction to: Diagnostic performance of preoperative MR imaging findings for differentiation of uterine leiomyoma with intraligamentous growth from subserosal leiomyoma.

Abdom Radiol (NY) 2021 Jul 16. Epub 2021 Jul 16.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

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http://dx.doi.org/10.1007/s00261-021-03208-3DOI Listing
July 2021

Automatic segmentation of uterine endometrial cancer on multi-sequence MRI using a convolutional neural network.

Sci Rep 2021 Jul 14;11(1):14440. Epub 2021 Jul 14.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto, 606-8507, Japan.

Endometrial cancer (EC) is the most common gynecological tumor in developed countries, and preoperative risk stratification is essential for personalized medicine. There have been several radiomics studies for noninvasive risk stratification of EC using MRI. Although tumor segmentation is usually necessary for these studies, manual segmentation is not only labor-intensive but may also be subjective. Therefore, our study aimed to perform the automatic segmentation of EC on MRI with a convolutional neural network. The effect of the input image sequence and batch size on the segmentation performance was also investigated. Of 200 patients with EC, 180 patients were used for training the modified U-net model; 20 patients for testing the segmentation performance and the robustness of automatically extracted radiomics features. Using multi-sequence images and larger batch size was effective for improving segmentation accuracy. The mean Dice similarity coefficient, sensitivity, and positive predictive value of our model for the test set were 0.806, 0.816, and 0.834, respectively. The robustness of automatically extracted first-order and shape-based features was high (median ICC = 0.86 and 0.96, respectively). Other high-order features presented moderate-high robustness (median ICC = 0.57-0.93). Our model could automatically segment EC on MRI and extract radiomics features with high reliability.
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http://dx.doi.org/10.1038/s41598-021-93792-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280152PMC
July 2021

Direct percutaneous access to a mesenteric vein for antegrade embolization of esophageal varices: A case report.

Radiol Case Rep 2021 Sep 3;16(9):2491-2495. Epub 2021 Jul 3.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

A 79-year-old woman with a history of advanced gastric cancer and portal vein tumor thrombus, treated with surgery and chemoradiotherapy, presented with hematemesis due to esophageal variceal bleeding around the esophagojejunal anastomosis. Endoscopic treatment was unsuccessful. Due to portal vein occlusion, percutaneous transhepatic access was difficult. Thus, the middle colic vein, which was dilated due to portal vein occlusion, was percutaneously punctured, and antegrade embolization of a jejunal vein feeding the varices was performed using a microcatheter through a 4-F dilator placed as a sheath. After embolization, the sheath was removed, and ultrasound-guided compression of the puncture site was performed. No bleeding complication occurred. Therefore, direct percutaneous access to a mesenteric vein is a viable alternative to transhepatic access.
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http://dx.doi.org/10.1016/j.radcr.2021.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259231PMC
September 2021

Evaluation of Weighted Diffusion Subtraction for Detection of Clinically Significant Prostate Cancer.

J Magn Reson Imaging 2021 Jun 4. Epub 2021 Jun 4.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Background: Diffusion-weighted imaging (DWI) is an important method for clinically significant prostate cancer (csPCa) diagnosis; however, the Prostate Imaging-Reporting and Data System (PI-RADS) requires the subjective assessment of "markedly hypointense or not" on apparent diffusion coefficient (ADC) map. We hypothesize that weighted diffusion subtraction (WDS) images, created by weighted subtraction of high and low b-value DWIs, might better show areas of ADC values below a set threshold, thus decreasing the subjectivity of the assessment.

Purpose: To evaluate the diagnostic ability of WDS for csPCa by comparing scores based on WDS images (DWI/WDS) with those based on PI-RADS DWI (DWI/ADC).

Study Type: Retrospective.

Subjects: Eighty-six PCa patients.

Field Strength/sequences: 3.0 T; DWI.

Assessment: Four readers assessed the probability of csPCa in lesions (overall, in the peripheral zone [PZ] and transitional zone [TZ]) using 5-point DWI/ADC and DWI/WDS scores. Prostatectomy specimens were the reference standard. ADC values and contrast between csPCa and normal prostate tissue on ADC maps and WDS images were calculated with reference to the pathological map.

Statistical Tests: Diagnostic ability was evaluated by Jackknife alternative free-response receiver-operating characteristic curve. Figure of merit (FOM), sensitivity, and positive predictive value (PPV) between the DWI/ADC and DWI/WDS scores were compared using paired t-test. Inter-reader agreement was analyzed using κ statistics, and the significance probability was calculated using the Z statistic. Wilcoxon signed-rank test was used to compare contrast between csPCa and normal prostate tissue on ADC maps and WDS images. A P value <0.05 was considered statistically significant.

Results: FOM and sensitivity of the DWI/WDS scores were significantly better than those of the DWI/ADC scores overall, in the PZ and TZ (FOM: overall, 0.715 vs. 0.783; PZ, 0.756 vs. 0.815; TZ, 0.653 vs. 0.738. Sensitivity: overall, 0.512 vs. 0.607; PZ, 0.485 vs. 0.573; TZ, 0.636 vs. 0.761). For PPV, a statistically significant difference was observed overall (0.727 vs. 0.777). The κ value of DWI/WDS score was significantly higher than that of DWI/ADC score overall and in the PZ (overall, 0.614 vs. 0.792; PZ, 0.609 vs. 0.797). Contrast was significantly higher overall in the PZ and TZ in WDS images (median, 1.26, 1.19, and 1.61) than in ADC maps (0.46, 0.47, and 0.41).

Data Conclusion: WDS images performed better than ADC maps in the diagnosis of csPCa and in inter-reader agreement of the diagnosis.

Level Of Evidence: 4 Technical Efficacy Stage: 2.
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http://dx.doi.org/10.1002/jmri.27771DOI Listing
June 2021

Diffuse Large B-cell Lymphoma: Unexpected Uptake Observed on Cardiac 123I-MIBG Scintigraphy.

Clin Nucl Med 2021 Oct;46(10):850-852

From the Departments of Diagnostic Imaging and Nuclear Medicine.

Abstract: A 77-year-old man with parkinsonism was referred to the department of neurology for further examination. Cardiac 123I-MIBG scintigraphy unexpectedly showed strong uptake in the left shoulder, suggestive of MIBG-avid tumors including paraganglioma. MRI revealed multiple nodules suggestive of lymphoma. A biopsy was performed, which led to the pathological diagnosis of diffuse large B-cell lymphoma. Cardiac MIBG scintigraphy sometimes shows unexpected findings outside the mediastinum. In addition, lymphoma should also be added to the list of differential diagnoses for MIBG-positive tumors.
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http://dx.doi.org/10.1097/RLU.0000000000003737DOI Listing
October 2021

Implications of the new FIGO staging and the role of imaging in cervical cancer.

Br J Radiol 2021 Sep 14;94(1125):20201342. Epub 2021 May 14.

Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

International Federation of Gynecology and Obstetrics (FIGO) staging, which is the fundamentally important cancer staging system for cervical cancer, has changed in 2018. New FIGO staging includes considerable progress in the incorporation of imaging findings for tumour size measurement and evaluating lymph node (LN) metastasis in addition to tumour extent evaluation. MRI with high spatial resolution is expected for tumour size measurements and the high accuracy of positron emmision tomography/CT for LN evaluation. The purpose of this review is firstly review the diagnostic ability of each imaging modality with the clinical background of those two factors newly added and the current state for LN evaluation. Secondly, we overview the fundamental imaging findings with characteristics of modalities and sequences in MRI for accurate diagnosis depending on the focus to be evaluated and for early detection of recurrent tumour. In addition, the role of images in treatment response and prognosis prediction is given with the development of recent technique of image analysis including radiomics and deep learning.
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http://dx.doi.org/10.1259/bjr.20201342DOI Listing
September 2021

Synthesis and biological evaluation of novel F-labeled phenylbenzofuran-2-carboxamide derivative for detection of orexin 1 receptor in the brain.

Bioorg Med Chem Lett 2021 07 10;43:128098. Epub 2021 May 10.

Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address:

Although the orexin 1 receptor (OXR) in the brain is considered to regulate reward and feeding, the in vivo function of OXR has not been fully elucidated. In vivo imaging of OXR with positron emission tomography (PET) may be useful to further understand the molecular details of OXR. In this study, we newly designed and synthesized a phenylbenzofuran-2-carboxamide (PBC) derivative ([F]PBC-1) and evaluated its utility as a PET probe targeting OXR in the brain. The results of cell binding assays suggested that [F]PBC-1 has affinity for OXR. In an in vitro competitive inhibition assay, PBC-1 showed selective binding affinity for OXR (IC = 19.5 nM) over orexin 2 receptor (IC = 456.7 nM). Furthermore, [F]PBC-1 displayed sufficient brain uptake for in vivo imaging with PET in a biodistribution study using normal mice, but in vivo instability was observed. These results suggest that further modifications for improvement of the pharmacokinetics are needed, but the PBC scaffold has potential for the development of useful PET probes targeting OXR in the brain.
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http://dx.doi.org/10.1016/j.bmcl.2021.128098DOI Listing
July 2021

Kinetic information from dynamic contrast-enhanced MRI enables prediction of residual cancer burden and prognosis in triple-negative breast cancer: a retrospective study.

Sci Rep 2021 May 12;11(1):10112. Epub 2021 May 12.

Department of Breast Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.

This study aimed to evaluate the predictions of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prognosis of triple-negative breast cancer (TNBC), especially with residual disease (RD) after preoperative chemotherapy. This retrospective analysis included 74 TNBC patients who received preoperative chemotherapy. DCE-MRI findings from three timepoints were examined: at diagnosis (MRI), at midpoint (MRI) and after chemotherapy (MRI). These findings included cancer lesion size, washout index (WI) as a kinetic parameter using the difference in signal intensity between early and delayed phases, and time-signal intensity curve types. Distant disease-free survival was analysed using the log-rank test to compare RD group with and without a fast-washout curve. The diagnostic performance of DCE-MRI findings, including positive predictive value (PPV) for pathological responses, was also calculated. RD without fast washout curve was a significantly better prognostic factor, both at MRI and MRI (hazard ratio = 0.092, 0.098, p < 0.05). PPV for pathological complete remission at MRI was 76.7% by the cut-off point at negative WI value or lesion size = 0, and 66.7% at lesion size = 0. WI and curve types derived from DCE-MRI at the midpoint of preoperative chemotherapy can help not only assess tumour response but also predict prognosis.
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http://dx.doi.org/10.1038/s41598-021-89380-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115642PMC
May 2021

Additional Value of [F]FDG PET or PET/CT for Response Assessment of Patients with Gastrointestinal Stromal Tumor Undergoing Molecular Targeted Therapy: A Meta-Analysis.

Diagnostics (Basel) 2021 Mar 8;11(3). Epub 2021 Mar 8.

Department of Diagnostic Radiology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.

To assess the additional value of 2-deoxy-2-[F] fluoro-d-glucose ([F]FDG) positron emission tomography (PET) or PET/CT over conventional morphological imaging techniques in the treatment response assessment of gastrointestinal stromal tumor (GIST) to molecular targeted therapy (MTT), we performed a meta-analysis of all the available studies to compare the predictive value of [F]FDG PET or PET/CT and conventional imaging techniques for assessing the response to MTT in GIST. We determined the sensitivities and specificities across studies, we calculated the positive and negative likelihood ratios (LR) and made summary receiver operating characteristic curves (SROC) using hierarchical regression models. Pooled analysis included 4 studies comprising 88 patients. The performance characteristics in [F]FDG PET or PET/CT and CT were as follows: sensitivity, 89% (95% confidence interval (CI) 78, 95), 52% (39, 64); specificity, 65% (44, 83), 92% (75, 99); diagnostic odds ratios (DOR), 5.8 (2.0, 16.8 4.9 (1.5, 16.1); positive LR, 1.9 (1.1, 3.4), 3.0 (1.1, 8.1); and negative LR, 0.23 (0.03, 1.6), 0.66 (0.42, 1.0), respectively. In SROC curves, the area under the curve (AUC) was 0.81 (SE, 0.11) and 0.71 (SE, 0.13) and the Q* index was 0.74 and 0.66, respectively. [F]FDG PET/CT had higher sensitivity, while DOR and SROC curves showed better diagnostic performance in [F]FDG PET and PET/CT studies as compared to CT.
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http://dx.doi.org/10.3390/diagnostics11030475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000740PMC
March 2021

Diagnostic performance of preoperative MR imaging findings for differentiation of uterine leiomyoma with intraligamentous growth from subserosal leiomyoma.

Abdom Radiol (NY) 2021 08 2;46(8):4036-4045. Epub 2021 Apr 2.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: To evaluate the diagnostic performance of MRI findings for differentiating uterine leiomyoma with intraligamentous growth, or broad ligament fibroid, from subserosal leiomyoma.

Methods: This study included 37 patients with surgically confirmed uterine smooth muscle tumors (36 leiomyomas and one smooth muscle tumor of uncertain malignant potential) with intraligamentous growth (IL) and size-matched control of 37 patients with subserosal leiomyoma (SS). Two radiologists independently evaluated eight preoperative MRI findings: tumor shape, degeneration, attachment to uterus, ovary elevation, ureter displacement, bladder deformation, rectal displacement, and separation of round ligament (RL) and uterine artery (UA). The diagnostic values of these findings and interobserver agreement were assessed. Receiver-operating characteristic (ROC) analysis of the number of positive MRI findings for diagnosing IL was performed. Clinical outcomes including surgical method, operation time, intraoperative blood loss, perioperative complications, and postoperative hospital stay of the two groups were compared.

Results: Significant differences in tumor shape, attachment to uterus, ovary elevation, ureter displacement, and separation of RL and UA were found between IL and SS. Four of these findings, excluding ureter displacement, showed moderate to substantial interobserver agreement. When two or more of these four findings were positive, sensitivity, specificity, and area under the ROC curve were 91%, 77%, 0.90 in reader 1 and 82%, 89%, 0.91 in reader 2. The operation time was significantly longer for IL than for SS.

Conclusion: Tumor shape, attachment to uterus, ovary elevation, and separation of RL and UA are useful MRI findings for differentiating intraligamentous leiomyoma from subserosal leiomyoma.
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http://dx.doi.org/10.1007/s00261-021-03042-7DOI Listing
August 2021

Convolutional neural network for classifying primary liver cancer based on triple-phase CT and tumor marker information: a pilot study.

Jpn J Radiol 2021 Jul 10;39(7):690-702. Epub 2021 Mar 10.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: To develop convolutional neural network (CNN) models for differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) and predicting histopathological grade of HCC.

Materials And Methods: Preoperative computed tomography and tumor marker information of 617 primary liver cancer patients were retrospectively collected to develop CNN models categorizing tumors into three categories: moderately differentiated HCC (mHCC), poorly differentiated HCC (pHCC), and ICC, where the histopathological diagnoses were considered as ground truths. The models processed manually cropped tumor with and without tumor marker information (two-input and one-input models, respectively). Overall accuracy was assessed using a held-out dataset (10%). Area under the curve, sensitivity, and specificity for differentiating ICC from HCCs (mHCC + pHCC), and pHCC from mHCC were also evaluated. We assessed two radiologists' performance without tumor marker information as references (overall accuracy, sensitivity, and specificity). The two-input model was compared with the one-input model and radiologists using permutation tests.

Results: The overall accuracy was 0.61, 0.60, 0.55, 0.53 for the two-input model, one-input model, radiologist 1, and radiologist 2, respectively. For differentiating pHCC from mHCC, the two-input model showed significantly higher specificity than radiologist 1 (0.68 [95% confidence interval: 0.50-0.83] vs 0.45 [95% confidence interval: 0.27-0.63]; p = 0.04).

Conclusion: Our CNN model with tumor marker information showed feasibility and potential for three-class classification within primary liver cancer.
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http://dx.doi.org/10.1007/s11604-021-01106-8DOI Listing
July 2021

The Rate of Apparent Diffusion Coefficient Change With Diffusion Time on Breast Diffusion-Weighted Imaging Depends on Breast Tumor Types and Molecular Prognostic Biomarker Expression.

Invest Radiol 2021 Aug;56(8):501-508

From the Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine.

Introduction: The aim of this study was to investigate the variation of apparent diffusion coefficient (ADC) values with diffusion time according to breast tumor type and prognostic biomarkers expression.

Materials And Methods: A total of 201 patients with known or suspected breast tumors were prospectively enrolled in this study, and 132 breast tumors (86 malignant and 46 benign) were analyzed. Diffusion-weighted imaging scans with 2 diffusion times were acquired on a clinical 3-T magnetic resonance imaging scanner using oscillating and pulsed diffusion-encoding gradients (effective diffusion times, 4.7 and 96.6 milliseconds) and b values of 0 and 700 s/mm2. Diagnostic performances to differentiate malignant and benign breast tumors for ADC values at short and long diffusion times (ADCshort and ADClong), ΔADC (the rate of change in ADC values with diffusion time), ADC0-1000 (ADC value from a standard protocol), and standard reading including dynamic contrast-enhanced magnetic resonance imaging (BI-RADS) were investigated. The correlations of ADCshort, ADClong, and ΔADC values with hormone receptor expression and breast cancer subtypes were also analyzed.

Results: The ADC values were lower, and ΔADC was higher in malignant tumors compared with benign tumors. The specificity of ADC values at all diffusion times and ΔADC values for differentiating malignant and benign breast tumors was superior to that of BI-RADS (87.0%-95.7% vs 73.9%), whereas the sensitivity was inferior (87.2%-90.7% vs 100%). Lower ADCshort and ADC0-1000 in ER-positive compared with ER-negative cancers (false discovery rate [FDR]-adjusted P = 0.037 and 0.018, respectively) and lower ADCshort, ADClong, and ADC0-1000 in progesterone receptor-positive compared with progesterone receptor-negative cancers (FDR-adjusted P = 0.037, 0.036, and 0.018, respectively) were found. Ki-67-positive cancers had larger ΔADCs than Ki-67-negative cancers (FDR-adjusted P = 0.018).

Conclusions: The ADC values vary with different diffusion time and vary in correlation with molecular biomarkers, especially Ki-67. Those results suggest that the diffusion time, which should be reported, might be a useful parameter to consider for breast cancer management.
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http://dx.doi.org/10.1097/RLI.0000000000000766DOI Listing
August 2021

Quantitative and qualitative evaluation of sequential PET/MRI using a newly developed mobile PET system for brain imaging.

Jpn J Radiol 2021 Jul 28;39(7):669-680. Epub 2021 Feb 28.

Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Purpose: To evaluate the clinical feasibility of a newly developed mobile PET system with MR-compatibility (flexible PET; fxPET), compared with conventional PET (cPET)/CT for brain imaging.

Methods: Twenty-one patients underwent cPET/CT with subsequent fxPET/MRI using F-FDG. As qualitative evaluation, we visually rated image quality of MR and PET images using a four-point scoring system. We evaluated overall image quality for MR, while we evaluated overall image quality, sharpness and lesion contrast. As quantitative evaluation, we compared registration accuracy between two modalities [(fxPET and MRI) and (cPET and CT)] measuring spatial coordinates. We also examined the accuracy of regional F-FDG uptake.

Results: All acquired images were of diagnostic quality and the number of detected lesions did not differ significantly between fxPET/MR and cPET/CT. Mean misregistration was significantly larger with fxPET/MRI than with cPET/CT. SUVmax and SUVmean for fxPET and cPET showed high correlations in the lesions (R = 0.84, 0.79; P < 0.001, P = 0.002, respectively). In normal structures, we also showed high correlations of SUVmax (R = 0.85, 0.87; P < 0.001, P < 0.001, respectively) and SUVmean (R = 0.83, 0.87; P < 0.001, P < 0.001, respectively) in bilateral caudate nuclei and a moderate correlation of SUVmax (R = 0.65) and SUVmean (R = 0.63) in vermis.

Conclusions: The fxPET/MRI system showed image quality within the diagnostic range, registration accuracy below 3 mm and regional F-FDG uptake highly correlated with that of cPET/CT.
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http://dx.doi.org/10.1007/s11604-021-01105-9DOI Listing
July 2021

Structure-Activity and Brain Kinetics Relationships of F-Labeled Benzimidazopyridine Derivatives as Tau PET Tracers.

ACS Med Chem Lett 2021 Feb 11;12(2):262-266. Epub 2021 Jan 11.

Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Noninvasive imaging of tau aggregates with a positron emission tomography (PET) tracer is useful for the diagnosis and staging of Alzheimer's disease (AD). Recently, we found that benzimidazopyridine (BIP) is an attractive scaffold for developing PET and single photon computed emission tomography tracers targeting tau aggregates. In this study, we designed and synthesized five novel F-labeled compounds with various substituted groups or atoms at the 7-position of the BIP scaffold. In autoradiographic studies, all F-labeled BIP derivatives selectively bound to tau aggregates deposited in AD brain sections. On the other hand, the initial brain uptake of these compounds was affected by the type of substituted group or halogen atom introduced into the 7-position of the BIP scaffold. Among these compounds, [F]Me-BIPF showed the highest brain uptake (6.79% ID/g at 2 min postinjection) and 2 min/60 min ratio (3.59). These results suggest that appropriate introduction of the substituted group or atom into the 7-position of the BIP scaffold may be effective for developing useful tau PET tracers.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883465PMC
February 2021

Diagnostic performance of Ga-DOTATOC PET/CT in tumor-induced osteomalacia.

Ann Nucl Med 2021 Mar 13;35(3):397-405. Epub 2021 Feb 13.

Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Objective: Tumor-induced osteomalacia (TIO) is caused by typically small tumors that secrete fibroblast growth factor 23 (FGF23). As tumor resection is the only effective treatment for TIO, it is important to detect the culprit tumor. We aimed to assess the utility of Gallium-DOTA-D-Phe(1)-Tyr(3)-octreotide (Ga-DOTATOC) PET/CT in TIO and the correlation between biochemical parameters and the PET/CT results.

Methods: Thirty-five patients with clinically suspected TIO who had undergone Ga-DOTATOC PET/CT were retrospectively analyzed. Ga-DOTATOC PET/CT results were compared with biochemical parameters and the final diagnosis, including histopathology.

Results: Ga-DOTATOC PET/CT detected focal uptake consistent with TIO in 21/35 patients, one of which was considered false positive. In 16 patients, the cause of osteomalacia was confirmed histologically as phosphaturic mesenchymal tumor (n = 15) or fibrous dysplasia (n = 1). The other four patients were judged clinically as true positive by subsequent MRI and the clinical course. Overall, the detection rate of Ga-DOTATOC PET/CT was 57% (20/35). Median tumor maximum standardized uptake value (SUVmax) was 6.9 (range 1.5-37.7). There was no significant difference in serum intact FGF23 level between DOTATOC-positive and DOTATOC-negative cases, and no significant correlation was observed between intact FGF23 level and tumor SUVmax.

Conclusions: Ga-DOTATOC PET/CT was clinically useful in detecting culprit tumors and subsequent patient management in TIO.
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http://dx.doi.org/10.1007/s12149-021-01575-xDOI Listing
March 2021

Increased [F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors.

EJNMMI Res 2021 Jan 25;11(1). Epub 2021 Jan 25.

Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-Ku, Kyoto, 606-8507, Japan.

Background: [F]Fluoromisonidazole ([F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [F]FMISO PET imaging.

Methods: FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan).

Results: FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUV ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05).

Conclusion: In this study, we revealed that MRP1 inhibitors increase [F]FMISO accumulation in hypoxic cells. This suggests that [F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.
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http://dx.doi.org/10.1186/s13550-021-00752-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835267PMC
January 2021

Evaluation of Optimal Post-Injection Timing of Hypoxic Imaging with F-Fluoromisonidazole-PET/CT.

Mol Imaging Biol 2021 08 21;23(4):597-603. Epub 2021 Jan 21.

Department of Radiation Oncology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.

Purpose: Positron emission tomography (PET)/computed tomography (CT) using F-fluoromisonidazole (FMISO) has been used as an imaging tool for tumour hypoxia. However, it remains unclear whether they are useful when scanning is performed earlier, e.g. at 2-h post-injection with a high sensitivity PET scanner. This study aimed to investigate the relationship between quantitative values in F-fluoromisonidazole (F-FMISO)-PET obtained at 2- and 4-h post-injection in patients with head and neck cancer.

Procedures: We enrolled 20 patients with untreated locally advanced head and neck cancer who underwent F-FMISO-PET/CT scan between August 2015 and March 2018 at our institute. Image acquisition was performed 2 h and 4 h after F-FMISO administration using a combined PET/CT scanner. The SUVmax, SUVmean, SUVpeak, tumour-to-blood ratio (TBR), tumour-to-muscle ratio (TMR), metabolic tumour volume (MTV), and total lesion hypoxia (TLH) were measured in the region of interest of the primary tumour. We evaluated the between-image Spearman's rank correlation coefficients and percentage differences in the quantitative values. The locations of the maximum uptake pixel were identified in both scans, and the distance between them was measured.

Results: The mean (SD) SUVmax at 2 h and 4 h was 2.2(0.7) and 2.4(0.8), respectively. The Spearman's rank correlation coefficients (ρ) and mean (SD) of the percentage differences of the measures were as follows: SUVmax (0.97; 7.0 [5.1]%), SUVmean (0.97; 5.2 [5.8]%), SUVpeak (0.94; 5.3 [4.7]%), TBR (0.96; 14.2 [9.8]%), TMR (0.96; 14.7 [8.4]%), MTV (0.98; 39.9 [41.3]%), and TLH (0.98; 40.1 [43.4]%). There were significant between-scan correlations in all quantitative values. The mean (SD) distance between the two maximum uptake pixels was 7.3 (5.3) mm.

Conclusions: We observed a high correlation between the quantitative values at 2 h and 4 h. When using a combined high-quality PET/CT, the total examination time for FMISO-PET can be shortened by skipping the 4-h scan.
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http://dx.doi.org/10.1007/s11307-021-01580-6DOI Listing
August 2021

Synthesis and evaluation of gallium-68-labeled nitroimidazole-based imaging probes for PET diagnosis of tumor hypoxia.

Ann Nucl Med 2021 Mar 9;35(3):360-369. Epub 2021 Jan 9.

Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Objective: In this study, we designed and synthesized four novel Ga-radiolabeled compounds ([Ga]DN-3, [Ga]DN-4, [Ga]NN-3, and [Ga]NN-4) composed of a nitroimidazole and two types of bifunctional chelates (DOTA or NOTA) via several alkyl linkers of different length. Then, we evaluated their properties as hypoxia imaging probes for positron emission tomography (PET) compared with conventional compounds ([Ga]DN-2 and [Ga]NN-2).

Methods: The precursors of Ga-radiolabeled compounds were synthesized through a two-step reaction, and then reacted with GaCl to be Ga-radiolabeled compounds. FaDu cells were treated with Ga-radiolabeled compounds and then incubated under normoxic (21% O) or hypoxic (1% O) conditions. The radioactivity of these cells was measured 2 h after incubation. The biodistribution and PET/CT imaging of Ga-radiolabeled compounds in FaDu-bearing Balb/c nude mice were evaluated 2 h after intravenous injection.

Results: The Ga-radiolabeled compounds were synthesized with radiochemical purities over 95%. In the in vitro study, the levels of Ga-radiolabeled compounds were significantly higher in hypoxic cells than in normoxic cells. In hypoxic cells, the compounds we designed in this study demonstrated higher accumulation than the conventional compounds. In the in vivo biodistribution study, [Ga]DN-3 exhibited the highest accumulation in tumor. In the in vivo PET/CT imaging study, the tumor tissues of the FaDu-xenografted mice were visualized at 2 h after intravenous administration of Ga-radiolabeled compounds.

Conclusions: Our study suggested that the length of the linkers connecting nitroimidazole to a bifunctional chelate affect PET imaging of hypoxic tumors with Ga-radiolabeled compounds.
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http://dx.doi.org/10.1007/s12149-020-01573-5DOI Listing
March 2021

Physiological FDG uptake in growth plate on pediatric PET.

Asia Ocean J Nucl Med Biol 2021 ;9(1):15-20

Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Japan.

Objectives: F-Fluorodeoxyglucose (FDG) uptake in children is different from that in adults. Physiological accumulation is known to occur in growth plates, but the pattern of distribution has not been fully investigated. Our aim was to evaluate the metabolic activity of growth plates according to age and location.

Methods: We retrospectively evaluated 89 PET/CT scans in 63 pediatric patients (male : female=25 : 38, range, 0-18 years). Patients were classified into four age groups (Group A: 0-2 years, Group B: 3-9 years, Group C: 10-14 years and Group D: 15-18 years). The maximum standardized uptake value (SUV) of the proximal and distal growth plates of the humerus, the forearm bones and the femur were measured. The SUV of each site and each age group were compared and statistically analyzed. We also examined the correlations between age and SUV.

Results: As for the comparison of SUV in each location, the SUV was significantly higher in the distal femur than those in the other sites (p< 0.01). SUV in the distal humerus and the proximal forearm bones were significantly lower than those in the other sites (p< 0.01). In the distal femur, there was large variation in SUV, while in the distal humerus and the proximal forearm bones, there was small variation. As for the comparison of SUV in each age group, the SUV in group D tended to be lower than those in the other groups, but in the distal femur, there was no significant difference among each age group.

Conclusion: Our data indicate that FDG uptake in growth plates varies depending on the site and age with remarkable uptake especially in the distal femur.
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http://dx.doi.org/10.22038/AOJNMB.2020.49638.1339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701234PMC
January 2021
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