Publications by authors named "Yoshito Tsushima"

239 Publications

Potential of three-step pretargeting radioimmunotherapy using biotinylated bevacizumab and succinylated streptavidin in triple-negative breast cancer xenograft.

Ann Nucl Med 2021 Apr 13;35(4):514-522. Epub 2021 Feb 13.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.

Objective: Pretargeting radioimmunotherapy (PRIT) is a promising approach that can reduce long-time retention of blood radioactivity and consequently reduce hematotoxicity. Among the PRIT strategies, the combination of biotin-conjugated mAb and radiolabeled streptavidin (StAv) is a simple and convenient method because of its ease of preparation. This study performed three-step (3-step) PRIT using the sequential injection of (1) biotinylated bevacizumab (Bt-BV), (2) avidin, and (3) radiolabeled StAv for the treatment of triple-negative breast cancer (TNBC).

Methods: Four biodistribution studies were performed using In in tumor-bearing mice to optimize each step of our PRIT methods. Further, a therapeutic study was performed with optimized 3-step PRIT using Y-labeled StAv.

Results: Based on the biodistribution studies, the protein dose of Bt-BV and avidin was optimized to 100 μg and 10 molar equivalent of BV, respectively. Succinylation of StAv significantly decreased the kidney accumulation level (with succinylation (6.96 ± 0.91) vs without succinylation (20.60 ± 1.47) at 1 h after injection, p < 0.0001) with little effect on the tumor accumulation level. In the therapeutic study, tumor growth was significantly suppressed in treatment groups with optimized 3-step PRIT using Y-labeled succinylated StAv compared to that of the no-treatment group (p < 0.05).

Conclusions: The 3-step PRIT strategy of this study achieved fast blood clearance and low kidney uptake with little effect on the tumor accumulation level, and a certain degree of therapeutic effect was consequently observed. These results indicated that the pretargeting treatment of the current study may be effective for human TNBC treatment.
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http://dx.doi.org/10.1007/s12149-021-01597-5DOI Listing
April 2021

Post-contrast Acute Kidney Injury Following Emergency Transcatheter Arterial Embolization for Uncontrollable Postpartum Hemorrhage.

Angiology 2021 Feb 11:3319721991367. Epub 2021 Feb 11.

Department of Radiology, Gunma University Hospital, Maebashi, Gunma, Japan.

The aim of this study was to investigate the incidence of post-contrast acute kidney injury (PC-AKI) in patients with uncontrollable postpartum hemorrhage undergoing emergency transcatheter arterial embolization (TAE). Data collected included patient characteristics, serum creatinine (SCr) level before and after TAE, iodine quantity of contrast media, time between computed tomography and TAE, diabetes mellitus, hemorrhage volume, and blood transfusion volume. For the diagnosis of PC-AKI, the criteria of the European Society of Urogenital Radiology Guidelines (version 10.0) were used. A total of 71 TAE procedures were performed over a 5-year period, and 47 patients met the inclusion criteria. Preprocedural renal function and change of SCr were positively correlated ( < .001), although no patients met the PC-AKI criteria and none showed renal impairment on the follow-up examination (95% upper confidence limit = 6.2%). Total iodine quantity was not correlated with SCr change. Postpartum hemorrhage was finally controlled in all 47 patients, and they were subsequently discharged. In conclusion, emergency TAE for patients with uncontrollable postpartum hemorrhage was a safe and effective procedure, not only in terms of bleeding-related and other outcomes but also with respect to the risk of PC-AKI.
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http://dx.doi.org/10.1177/0003319721991367DOI Listing
February 2021

Unexpected -[18F] fluoro-2-deoxy-D-glucose accumulation in subarachnoid hemorrhage due to an aneurysm rupture.

Radiol Case Rep 2021 Mar 8;16(3):684-686. Epub 2021 Jan 8.

Department of Diagnostic and Interventional Radiology, Gunma University Hospital, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 Japan.

A 79-year-old Asian man with paranasal cancer underwent 2-[18F] fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) to evaluate metastatic lesions. Unexpected FDG accumulation during subarachnoid hemorrhage due to an aneurysm rupture visualized with FDG-PET/CT. It is rare to encounter life-threatening diseases in FDG-PET/CT because FDG-PET/CT is usually scheduled beforehand. However, an immediate response is warranted in unexpected conditions. Physicians who perform FDG-PET/CT should be familiar with life-threatening FDG-PET findings.
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http://dx.doi.org/10.1016/j.radcr.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809252PMC
March 2021

Subtype-dependent difference of glucose transporter 1 and hexokinase II expression in craniopharyngioma: an immunohistochemical study.

Sci Rep 2021 Jan 8;11(1):126. Epub 2021 Jan 8.

Department of Neurosurgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Papillary craniopharyngiomas are characterized by the BRAF V600E mutation. Enhancement of glucose metabolism may be involved in the downstream of the BRAF V600E mutation in many types of tumors. Glucose metabolism was investigated in craniopharyngioma using immunohistochemical analysis. The study included 29 cases of craniopharyngioma (18 adamantinomatous type [ACP], 11 papillary type [PCP]). Immunohistochemical analysis was performed with anti-glucose transporter-1 (GLUT-1), anti-hexokinase-II (HK-II), anti-BRAF V600E, and anti-beta-catenin antibodies. Expressions of GLUT-1 and HK-II were evaluated using a semiquantitative 4-tiered scale as 0, 1+, 2+, 3+, and divided into negative (0 or 1+) or positive (2+ or 3+) group. GLUT-1 expression level was significantly higher in PCPs than ACPs (0, 1+, 2+, 3+ = 2, 12, 4, 0 cases in ACP, respectively, 0, 1+, 2+, 3+ = 0, 2, 5, 4 in PCP, p = 0.001), and most PCPs were classified into positive group (positive rate, 22.2% [4/18] in ACP, 81.8% [9/11] in PCP; p = 0.003). HK-II expression was also conspicuous in PCPs (0, 1+, 2+, 3+ = 7, 9, 2, 0 cases in ACP, 0, 3, 3, 5 in PCP; p = 0.001), and most of them divided into positive group (positive rate, 11.1% [2/18] in ACP, 72.7% [8/11] in PCP; p = 0.001). Expression patterns of BRAF V600E and beta-catenin reflected the clinicopathological subtypes. Both GLUT-1 and HK-II expressions were prominent in PCP. Glucose metabolism might be more enhanced in PCP than ACP. PCP may use the glucose metabolic system downstream of the BRAF V600E mutant protein.
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http://dx.doi.org/10.1038/s41598-020-80259-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794328PMC
January 2021

Absorbed dose simulation of meta-At-astato-benzylguanidine using pharmacokinetics of I-MIBG and a novel dose conversion method, RAP.

Ann Nucl Med 2021 Jan 22;35(1):121-131. Epub 2020 Nov 22.

Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, 1233 Watanuki-machi, Takasaki, 370-1292, Japan.

Objective: We aimed to estimate in vivo At-labeled meta-benzylguanidine (At-MABG) absorbed doses by the two dose conversion methods, using I-MIBG biodistribution data from a previously reported neuroblastoma xenograft model. In addition, we examined the effects of different cell lines and time limitations using data from two other works.

Methods: We used the framework of the Monte Carlo method to create 3200 virtual experimental data sets of activity concentrations (kBq/g) to get the statistical information. Time activity concentration curves were produced using the fitting method of a genetic algorithm. The basic method was that absorbed doses of At-MABG were calculated based on the medical internal radiation dose formalism with the conversion of the physical half-life time of I to that of At. We have further improved the basic method; that is, a novel dose conversion method, RAP (Ratio of Pharmacokinetics), using percent injected dose/g.

Results: Virtual experiments showed that At-MABG and I-MIBG had similar properties of initial activity concentrations and biological components, but the basic method did not simulate the At-MABG dose. Simulated At-MABG doses from I-MIBG using the RAP method were in agreement with those from At-MABG, so that their boxes overlapped in the box plots. The RAP method showed applicability to the different cell lines, but it was difficult to predict long-term doses from short-term experimental data.

Conclusions: The present RAP dose conversion method could estimate At-MABG absorbed doses from the pharmacokinetics of I-MIBG with some limitations. The RAP method would be applicable to a large number of subjects for targeted nuclide therapy.
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http://dx.doi.org/10.1007/s12149-020-01548-6DOI Listing
January 2021

The effect of abolishing instructions to fast prior to contrast-enhanced CT on the incidence of acute adverse reactions.

Insights Imaging 2020 Oct 23;11(1):113. Epub 2020 Oct 23.

Department of Radiology, Gunma University Hospital, Maebashi, Japan.

Objectives: To evaluate the effect of abolishing instructions to fast prior to contrast-enhanced CT on acute adverse reactions (AARs).

Methods: In our institution, we instructed patients to fast one meal before contrast-enhanced CT examinations. However, we abolished these instructions at the end of March 2019, and solid food intake was not restricted before contrast-enhanced CT after this date. The differences in the incidence of AARs before (December 2015-November 2018, n = 43,927) and after (April 2019-March 2020, n = 14,676) abolishing instructions to fast were compared. We allowed 4 months (December 2018-March 2019) for this policy change to fully permeate the CT referrals. The medical records of patients who vomited were retrospectively reviewed by one of the authors for notations of aspiration or aspiration pneumonia attributable to vomiting.

Results: The overall incidence of AARs before (1.60%, n = 705) and after abolition (1.40%, n = 205) did not change significantly. As the chemotoxic reactions, the incidence of nausea decreased significantly (0.31 to 0.18%, p = 0.006). The incidence of vomiting did not change (0.12 to 0.16%), and there were no cases of aspiration pneumonia attributable to vomiting during the study period. The incidence of severe hypersensitivity/allergy-like reactions did not change (0.06 to 0.05%).

Conclusions: Abolishing instructions to fast decreased the incidence of nausea, but did not affect the incidence of vomiting. No cases of aspiration pneumonia attributable to vomiting were found. Our study confirmed that fasting is not required prior to contrast-enhanced CT.
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http://dx.doi.org/10.1186/s13244-020-00918-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584708PMC
October 2020

[Improved Neural Imaging Sequence and Comparison with Conventional Methods].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2020 ;76(9):928-935

Department of Radiology, Gunma University Hospital.

The purpose of this study was to improve the contrast between the nerves and blood by reconsidering the imaging parameters of the sampling perfection with application-optimized contrasts using different flip angle evolutions (SPACE) method, and to compare it with conventional methods, including the constructive interference in steady state (CISS) and T-weighted SPACE (T2-SPACE) methods. In the phantom study, the repetition time (TR), echo time (TE), flip angle (FA), and turbo factor (TF) of SPACE were varied using the restore pulse. The parameters for which the nerve-blood contrast (C1) and cerebrospinal fluid-nerve contrast (C2) were equal were selected. Though multiple conditions resulted in C1 and C2 equivalence, we determined/set the TR=500 ms, TE=21 ms,  FA=120°, and  TF=30, considering the acquisition time, specific absorption rate (SAR), and artifacts. This sequence was called "short TR and short TE SPACE with restore pulse (SSSR)". In the phantom and healthy volunteer studies, the contrast between the nerves and blood in the SSSR method was statistically superior in both the physical and visual assessments compared with conventional methods. In the healthy volunteer study, C1 improved from 0.08 for CISS and 0.18 for T2-SPACE to 0.43 for SSSR. This is because the nerve signals in conventional methods were low due to the heavy T-weighted, while those in the SSSR method were high due to the short TE and effect of the restore pulse. In conclusion, the contrast between the nerves and blood was significantly higher in the SSSR method compared with conventional methods.
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http://dx.doi.org/10.6009/jjrt.2020_JSRT_76.9.928DOI Listing
September 2020

Preclinical evaluation of new α-radionuclide therapy targeting LAT1: 2-[At]astato-α-methyl-L-phenylalanine in tumor-bearing model.

Nucl Med Biol 2020 Nov - Dec;90-91:15-22. Epub 2020 Aug 26.

Department of Radiation-Applied Biology Research, Quantum Beam Science Research Directorate, National Institute for Quantum and Radiological Science and Technology, 1233 Watanuki-machi, Takasaki, Gunma 370-1292, Japan.

Introduction: Targeted α-radionuclide therapy has attracted attention as a promising therapy for refractory cancers. However, the application is limited to certain types of cancer. Since L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers, we prepared an LAT1-selective α-radionuclide-labeled amino acid analog, 2-[At]astato-α-methyl-L-phenylalanine (2-[At]AAMP), and evaluated its potential as a therapeutic agent.

Methods: 2-[At]AAMP was prepared from the stannyl precursor. Stability of 2-[At]AAMP was evaluated both in vitro and in vivo. In vitro studies using an LAT1-expressing human ovarian cancer cell line, SKOV3, were performed to evaluate cellular uptake and cytotoxicity of 2-[At]AAMP. Biodistribution and therapeutic studies in SKOV3-bearing mice were performed after intravenous injection of 2-[At]AAMP.

Results: 2-[At]AAMP was stable in murine plasma in vitro and excreted intact into urine. Cellular uptake of 2-[At]AAMP was inhibited by treatment with an LAT1-selective inhibitor. After 24 h incubation, 2-[At]AAMP suppressed clonogenic growth at 10 kBq/ml, and induced cell death and DNA double-strand breaks at 25 kBq/ml. When injected into mice, 2-[At]AAMP exhibited peak accumulation in the tumor at 30 min postinjection, and radioactivity levels in the tumor were retained up to 60 min. The majority of the radioactivity was rapidly eliminated from the body into urine in an intact form immediately after injection. 2-[At]AAMP significantly improved the survival of mice (P < 0.05) without serious side effects.

Conclusion: 2-[At]AAMP showed α-radiation-dependent cellular growth inhibition after it was taken up via LAT1. In addition, 2-[At]AAMP had a beneficial effect on survival in vivo. These findings suggest that 2-[At]AAMP would be useful for the treatment of LAT1-positive cancer.

Advances In Knowledge And Implications For Patient Care: This is the first report of an LAT1-targeting radiopharmaceutical for α-radionuclide therapy; this agent would be applicable for the treatment of various types of cancer.
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http://dx.doi.org/10.1016/j.nucmedbio.2020.08.003DOI Listing
August 2020

Evaluation of a Correction Method for In-Pentetreotide SPECT Imaging of Gastroenteropancreatic Neuroendocrine Tumors.

J Nucl Med Technol 2020 Dec 4;48(4):326-330. Epub 2020 Sep 4.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan; and.

The number of patients with the extremely rare disease gastroenteropancreatic (GEP) neuroendocrine tumor (NET) has increased rapidly in recent years. In-pentetreotide SPECT in somatostatin receptor scintigraphy has been used for the assessment of GEP NET patients. To diagnose GEP NET, appropriate selection of image correction parameters is critical. Correction methods may improve the In-pentetreotide SPECT image quality, but there is currently no standard technique. The purpose of this study was to determine the optimal correction parameter settings for In-pentetreotide SPECT. A phantom study produced images with a tumor-to-background ratio of as high as 16:1. A triple energy window was used for scatter correction (SC), and attenuation correction (AC) was CT-based. Correlation analysis was performed in 4 groups: no correction (NC), SC, AC, and combined SC with AC (CC). The In-pentetreotide SPECT results for 20 randomly selected patients (13 men and 7 women; age range, 37-81 y) with confirmed GEP NET were analyzed using data collected 4 h after injection of 111 MBq of In-pentetreotide. Emission data were reconstructed using ordered-subset expectation maximization (OSEM) with different settings. Different combinations of the correction parameters were used to analyze the contrast-to-noise ratios (CNRs) obtained with the phantom. In the clinical study, 20 GEP NET patients were used to evaluate the GEP NET lesion CNR by 4 different image correction methods obtained from In-pentetreotide SPECT images: NC, SC, AC, and CC. NC was used as a reference method. The phantom study revealed that the optimal energy window in the photopeak for somatostatin receptor scintigraphy was 171 keV ± 10% and 245 keV ± 7.5%, and the optimal OSEM reconstruction conditions were 8 subsets and 6 iterations. Among the OSEM collection conditions, CC produced a significantly higher CNR than NC or SC ( < 0.05). In the clinical study, CC was found to increase the CNR ( < 0.05). CC improves the correction in In-pentetreotide SPECT studies, compared with NC, providing better contrast and sharper outlines of lesions and organs.
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http://dx.doi.org/10.2967/jnmt.120.249680DOI Listing
December 2020

Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses.

Front Neurol 2020 11;11:757. Epub 2020 Aug 11.

Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (IBMPFD) presents with multiple symptoms and an unknown etiology. Valosin-containing protein () has been identified as the main causative gene of IBMPFD. However, no studies on neurofilament light chain (NFL) as a cerebrospinal fluid (CSF) marker of axonal neurodegeneration or on YKL-40 as a CSF marker of glial neuroinflammation have been conducted in IBMPFD patients with mutations. A 65-year-old man presented with progressive muscle atrophy and weakness of all limbs, non-fluent aphasia, and changes in personality and behavior. Cerebral MRI revealed bilateral frontal and temporal atrophy. Tc-HMDP bone scintigraphy and pelvic CT revealed remodeling changes and active osteoblastic accumulations in the right medial iliac bone. Muscle biopsy demonstrated multiple rimmed vacuoles in muscle cells with myogenic and neurogenic pathological alterations. After the patient was clinically diagnosed with IBMPFD, DNA analysis of the gene revealed a cytosine (C) to thymine (T) (C→ T) mutation, resulting in an amino acid exchange of arginine to cysteine (p.R155C mutation). The CSF levels of NFL at two time points (12 years apart) were higher than those in non-dementia controls (CTR) and Alzheimer's disease (AD); lower than those in frontotemporal dementia with motor neuron disease (FTD-MND); and comparable to those in patients with behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The CSF levels of YKL-40 were comparable at both time points and higher than those in CTR; lower than those in FTD-MND; and comparable to those in bvFTD, PSP, CBS, and AD. The CSF levels of phosphorylated tau 181 (P-Tau) and total tau (T-Tau) were not significantly different from those in CTR and other neurodegenerative diseases, except those in AD, which were significantly elevated. This is the first report that demonstrates increased NFL and YKL-40 CSF levels in an IBMPFD patient with a mutation (p.R155C); NFL and YKL-40 levels were comparable to those in bvFTD, PSP, CBS, and AD and higher than those in CTR. Our results suggest that IBMPFD neuropathology may involve both axonal neurodegeneration and glial neuroinflammation.
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http://dx.doi.org/10.3389/fneur.2020.00757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431878PMC
August 2020

Diffusion-Weighted MRI Predicts Lymph Node Metastasis and Tumor Aggressiveness in Resectable Pancreatic Neuroendocrine Tumors.

World J Surg 2020 Dec 14;44(12):4136-4141. Epub 2020 Aug 14.

Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan.

Objectives: The aim of this study was to identify whether diffusion-weighted magnetic resonance imaging (DW-MRI) can predict the malignant behavior of preoperative well-differentiated pancreatic neuroendocrine tumors (PanNETs).

Method: Forty patients with PanNETs who underwent pancreatectomy were enrolled in this study. The apparent diffusion coefficient (ADC) values were measured. Clinicopathological factors were compared in patients with high ADC and low ADC values and in patients with and without lymph node metastasis (LNM).

Result: The low ADC group was significantly associated with higher Ki-67 index, higher mitotic count, larger tumor size, higher rate of LNM, and venous invasion. In patients with low ADC values, the incidence of LNMs was 33.3%. In patients with high ADC values, there were no patients with LNM being 0%. A significant negative correlation was found between the mean ADC values and the Ki-67 index and between the mean ADC values and the mitotic count. In multivariate analysis, neural invasion and mean ADC values ≤ 1458 were independent predictors of LNM.

Conclusion: ADC values obtained using DW-MRI in the preoperative assessment of patients with PanNETs might be a useful predictor of malignant potential, especially LNM.
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http://dx.doi.org/10.1007/s00268-020-05736-3DOI Listing
December 2020

Improvement of diagnostic accuracy of Parkinson's disease on I-123-ioflupane single photon emission computed tomography (I FP-CIT SPECT) using new Japanese normal database.

Asia Ocean J Nucl Med Biol 2020 ;8(2):95-101

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.

Objectives: I-123-ioflupane single photon emission computed tomography (FP-CIT-SPECT) has been used to assess dopamine transporter (DAT) loss in Parkinson's disease. The specific binding ratio (SBR), a quantitative parameter of DAT density in the striatum, may be affected by differences in age, sex, and SPECT system. The purpose of this study was to evaluate the utility of FP-CIT-SPECT using the Japanese normal database (NDB) in the diagnosis of Parkinson's disease.

Methods: To standardize the quantitative outcome measures of DAT density obtained with different SPECT systems, striatal phantoms filled with striatal to background materials at ratios between 8:1 and 1:1 were measured using a gamma camera (ECAM) in our institute. Consecutive fifty patients (23 men and 27 women; age range, 40-86 years) with suspected PD undergoing FP-CIT SPECT brain imaging during the period from April to October 2016 were enrolled in this retrospective study. Their final diagnoses were PD in 28 patients and PD in 22 patients. SBRs of the patients were calculated using either new (Japanese database with different age and sex; NEWver) or old (non-Japanese database not specifying age and sex; OLDver) version software (AZE Virtual Place Hayabusa [DaTView], AZE, Ltd. Tokyo, Japan). The McNemar test was used to compare the diagnostic accuracy between old and new versions.

Results: Based on the phantom study, the calibrated SBR could be calculated by Y=1.25×Measured SBR+0.78. The sensitivities for OLDver and NEWver were 100% and 93%, respectively (p=0.5), and the specificities were 55% and 100% (p=0.002). The diagnostic accuracy of NEWver (96%) was better than that of OLDver (80%, p<0.001).

Conclusion: FP-CIT-SPECT using the Japanese NDB improved the diagnostic accuracy of PD by improving specificity.
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http://dx.doi.org/10.22038/AOJNMB.2019.43685.1290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354240PMC
January 2020

Does periodontitis affect the treatment response of biologics in the treatment of rheumatoid arthritis?

Arthritis Res Ther 2020 07 25;22(1):178. Epub 2020 Jul 25.

Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, Showa-machi 3-39-15, Maebashi, Gunma, 371-8511, Japan.

Background: Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and the treatment response to biologics in RA patients using FDG-PET/CT.

Methods: Sixty RA patients (male, n = 14; female, n = 46; average age, 58.3 years) treated with biologic agents were included in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The maximum standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in periodontal tissue and joints including the bilateral shoulders, elbows, wrists, hip, knees, and ankle joints. The Disease Activity Score (DAS) 28-CRP and the following clinical parameters were assessed: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and matrix metalloproteinase 3 (MMP-3). The relationship between the treatment response of RA and the baseline SUVmax of the periodontal tissue was evaluated.

Results: The baseline periodontal SUVmax was related to patient age (r = 0.302, p = 0.009) and the ACPA level (r = 0.265, p = 0.025). The DAS28-CRP, CRP, ESR, MMP-3, and joint SUVmax values were significantly decreased after 6 months of biological therapy. However, the mean periodontal SUVmax, ACPA, and RF showed no significant changes after treatment. There was a significantly negative correlation between the baseline periodontal SUVmax and the treatment response of DAS28-CRP (r = - 0.369, p = 0.004).

Conclusion: There was a negative correlation between the extent of PD at baseline and the treatment response of RA patients who received biological therapy. The evaluation of the periodontal condition is considered to be an essential part for the management of RA.
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http://dx.doi.org/10.1186/s13075-020-02269-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382136PMC
July 2020

Does periodontitis affect the treatment response of biologics in the treatment of rheumatoid arthritis?

Arthritis Res Ther 2020 07 25;22(1):178. Epub 2020 Jul 25.

Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, Showa-machi 3-39-15, Maebashi, Gunma, 371-8511, Japan.

Background: Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and the treatment response to biologics in RA patients using FDG-PET/CT.

Methods: Sixty RA patients (male, n = 14; female, n = 46; average age, 58.3 years) treated with biologic agents were included in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The maximum standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in periodontal tissue and joints including the bilateral shoulders, elbows, wrists, hip, knees, and ankle joints. The Disease Activity Score (DAS) 28-CRP and the following clinical parameters were assessed: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and matrix metalloproteinase 3 (MMP-3). The relationship between the treatment response of RA and the baseline SUVmax of the periodontal tissue was evaluated.

Results: The baseline periodontal SUVmax was related to patient age (r = 0.302, p = 0.009) and the ACPA level (r = 0.265, p = 0.025). The DAS28-CRP, CRP, ESR, MMP-3, and joint SUVmax values were significantly decreased after 6 months of biological therapy. However, the mean periodontal SUVmax, ACPA, and RF showed no significant changes after treatment. There was a significantly negative correlation between the baseline periodontal SUVmax and the treatment response of DAS28-CRP (r = - 0.369, p = 0.004).

Conclusion: There was a negative correlation between the extent of PD at baseline and the treatment response of RA patients who received biological therapy. The evaluation of the periodontal condition is considered to be an essential part for the management of RA.
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http://dx.doi.org/10.1186/s13075-020-02269-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382136PMC
July 2020

Efficiency of regional functional liver volume assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging for hepatocellular carcinoma with portal vein tumor thrombus.

Surg Today 2020 Nov 1;50(11):1496-1506. Epub 2020 Jul 1.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Purpose: We investigated whether functional future remnant liver volume (fFRLV), assessed using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), could evaluate regional liver function in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and help establish the indication for hepatectomy.

Methods: The subjects of this study were 12 patients with PVTT [PVTT(+) group] and 58 patients without PVTT [PVTT(-) group], from among 191 patients who underwent hepatectomy of more than one segment for HCC. We calculated the liver-to-muscle ratio (LMR) in the remnant liver, using EOB-MRI and fFRLV. Preoperative factors and surgical outcome were compared between the groups. The LMR of the area occluded by PVTT was compared with that of the non-occluded area.

Results: The indocyanine green retention rate at 15 min (ICG-R15) and liver fibrosis indices were increased in the PVTT(+) group, but the surgical outcomes of patients in this group were acceptable, with no liver failure, no mortality, and no differences from those in the PVTT(-) group. The fFRLV in the PVTT(+) group was not significantly different from that in the PVTT(-) group (p = 0.663). The LMR was significantly lower in the occluded area than in the non-occluded area (p = 0.004), indicating decreased liver function.

Conclusion: Assessing fFRLV using EOB-MRI could be useful for evaluating regional liver function and establishing operative indications for HCC with PVTT.
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http://dx.doi.org/10.1007/s00595-020-02062-yDOI Listing
November 2020

Safety and Efficacy of Aortic Vs Internal Iliac Balloon Occlusion for Cesarean Delivery in Coexisting Placenta Accreta and Placenta Previa.

Cardiovasc Intervent Radiol 2020 Sep 12;43(9):1277-1284. Epub 2020 Jun 12.

Department of Obstetrics and Gynecology, Gunma University Hospital, 3-39-33 Showa-machi, Maebashi, Gunma, Japan.

Purpose: To investigate safety and efficacy of intra-aortic balloon occlusion (IABO) versus internal iliac artery balloon occlusion (IIABO) for cesarean delivery in coexisting placenta accreta and placenta previa.

Materials And Methods: From 2006 to 2019, 60 pregnant women who had undergone preoperative IABO (n = 28) and IIABO (n = 32) for cesarean delivery in coexisting placenta accreta and placenta previa were retrospectively identified, and their medical records and relevant imaging were reviewed.

Results: Maternal characteristics (age, gravidity, previous cesarean delivery, gestational age, and neonatal weight) were similar in both groups. Estimated blood loss, volume of blood transfusion, length of hospitalization, and rate of hysterectomy were not significantly different between the groups. Operation time (the duration of cesarean delivery and hysterectomy, p < 0.05), total time of balloon occlusion (p < 0.01), and fetal radiation dose (p < 0.001) in the IABO group were less than in the IIABO group. No severe complications related to the balloon occlusion procedure were noted in either group.

Conclusion: IABO and IIABO are safe and effective options for cesarean delivery in patients with combined placenta accreta and placenta previa. The average operation time, balloon occlusion time, and fetal radiation dose in patients with IABO are less than in patients with IIABO. There were no complications related to balloon occlusion of the aorta or internal iliac artery.
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http://dx.doi.org/10.1007/s00270-020-02548-9DOI Listing
September 2020

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma.

Cancer Sci 2020 Jun 12;111(6):1969-1978. Epub 2020 May 12.

Division of Gastroenterological Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Japan.

The relationship between the local immune status and cancer metabolism regarding F-FDG and F-FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty-one ESCC patients who underwent F-FDG PET and F-FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD-1), CD8, Ki-67, CD34, GLUT1 ( F-FDG transporter) and LAT1 ( F-FAMT transporter). ESCC specimens with high tumoral PD-L1 and high CD8-positive lymphocytes were considered to have "hot tumor immune status." High PD-L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8-positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki-67 labelling index (P = 0.009) and CD34-positive vessel counts (P < 0.001). SUVmax of F-FDG was significantly higher in high PD-L1 cases than in low PD-L1 cases (P = 0.009). SUVmax of F-FAMT was significantly higher in high PD-L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of F-FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.
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http://dx.doi.org/10.1111/cas.14421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293073PMC
June 2020

Cu-ATSM and Tc(CO)-DCM20 potential in the early detection of rheumatoid arthritis.

Mod Rheumatol 2021 Mar 23;31(2):350-356. Epub 2020 Apr 23.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.

Objectives: Molecular imaging constitutes a promising technique for the early detection of rheumatoid arthritis (RA). Macrophages and hypoxia play significant roles in inflamed synovium. In the present study, we evaluated the efficacy of radiopharmaceuticals that target macrophage mannose receptors (Tc-labeled mannosylated dextran or Tc(CO)-DCM20) and hypoxia (copper(II) diacetyl-di(N-methylthiosemicarbazone) or Cu-ATSM) for the early detection of RA in collagen-induced arthritis (CIA) mice models.

Methods: CIA model was developed in DBA/1 mice, and the clinical score for arthritis was visually assessed on a regular basis. Two biodistribution studies were performed in a paired-labeled format using 2-deoxy-2-F-fluoro-D-glucose (F-FDG) as a reference: (1) Tc(CO)-DCM20 with F-FDG and (2) Cu-ATSM with F-FDG.

Results: The accumulation levels of Tc(CO)-DCM20 and Cu-ATSM in forepaws, hindpaws, and knee joints of CIA mice were significantly higher than that of control mice. In contrast, F-FDG uptake in hindpaws and knee joints showed no significant difference between CIA and control mice. The radioactivity levels of Tc(CO)-DCM20 and Cu-ATSM were significantly correlated with the clinical scores for the paws.

Conclusion: These results suggest the potential usefulness of Tc(CO)-DCM20 and radiolabeled Cu-ATSM for the imaging and early detection of RA.
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http://dx.doi.org/10.1080/14397595.2020.1751945DOI Listing
March 2021

Selective synthesis of L-2-[ F]fluoro-alpha-methylphenylalanine via copper-mediated F-fluorination of (mesityl)(aryl)iodonium salt.

J Labelled Comp Radiopharm 2020 06 28;63(8):368-375. Epub 2020 Apr 28.

Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.

L-2-[ F]fluoro-alpha-methylphenylalanine (2-[ F]FAMP) is a promising amino acid tracer for positron emission tomography (PET) imaging, yet the low production yield of direct electrophilic radiofluorination with [ F]F necessitates further optimization of the radiolabeling process. This paper describes a two-step preparation method for L-2-[ F]fluoro-alpha-methylphenylalanine (2-[ F]FAMP) starting from [ F]fluoride. The (Mesityl)(L-alpha-methylphenylalanine)-2-iodonium tetrafluoroborate precursors with various protecting groups were prepared. The copper-mediated F-fluorination of the iodonium salt precursors successfully produced 2-[ F]FAMP. The highest radio chemical conversion of 57.6% was noted with N-Piv-protected (mesityl)(aryl)iodonium salt in the presence of 5 equivalent of Cu (OTf) . Subsequent deprotection with 57% hydrogen iodide produced 2-[ F]FAMP within 120 min in 21.4 ± 11.7% overall radiochemical yield with >95% radiochemical purity and an enantiomeric excess >99%. The obtained 2-[ F]FAMP showed comparable biodistribution profiles in normal mice with that of the carrier-added 2-[ F]FAMP. These results indicate that usefulness of copper mediated F-fluorination for the production of 2-[ F]FAMP, which would facilitate clinical translation of the promising tumor specific amino acid tracer. Individual facilities could adopt either production method based on radioactivity demand and equipment availability.
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http://dx.doi.org/10.1002/jlcr.3840DOI Listing
June 2020

Quantitative analysis of metabolic parameters at F-fluorodeoxyglucose positron emission tomography in predicting malignant potential of anterior mediastinal tumors.

Oncol Lett 2020 Mar 9;19(3):1865-1871. Epub 2020 Jan 9.

Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.

To evaluate the utility of F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for predicting the malignancy of anterior mediastinal tumors, the present study retrospectively examined a total of 105 consecutive patients who underwent surgical resection of anterior mediastinal tumors at Gunma University Hospital after undergoing a preoperative FDG-PET scan. Patients were divided into benign and malignant groups in accordance with the following three classification systems: i) Clinical classification, benign or malignant (thymoma and carcinoma); ii) recurrence-based classification, low-risk recurrence (benign and low-risk thymoma) or high-risk recurrence (high-risk thymoma and carcinoma); and iii) pathological classification, benign (benign and thymoma) or malignant (carcinoma). The present study analyzed the differences between the benign and malignant groups in terms of FDG-PET parameters, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The malignant group exhibited a significantly greater SUVmax than the benign group according to all classification systems. By contrast, there was only a slight difference between groups in volume-based metabolic parameters (MTV and TLG) using the clinical classification, and no intergroup differences using the recurrence-based and pathological classifications. The area under the curve in receiver-operating characteristic curve analysis for predicting malignancy was significantly greater for SUVmax than for volume-based metabolic parameters using all classification methods. The respective optimal cut-off value, sensitivity and specificity of SUVmax to predict malignancy were 1.77, 92.0 and 87.0% for the clinical classification, 2.54, 93.6 and 60.3% for the recurrence-based classification, and 5.15, 78.9 and 90.7% for the pathological classification. SUVmax was the most useful parameter for predicting the malignancy of anterior mediastinal tumors.
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http://dx.doi.org/10.3892/ol.2020.11276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038926PMC
March 2020

Possible solution for the problem of unread image interpretation reports: the "Gunma University Star Search".

Jpn J Radiol 2020 Jul 17;38(7):643-648. Epub 2020 Mar 17.

Department of Healthcare Quality and Safety, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, Japan.

Purpose: To propose a new strategy to prevent communication errors caused by unread radiology reports.

Materials And Methods: Medical emergencies were prefixed with triple stars on radiology reports, and the attending physician was contacted by telephone. Semi-emergencies (medical issues needing addressing within 2 weeks) were prefixed with double stars. Two weeks later, the duty radiologist would search the double-starred reports, and reviewed relevant patient charts to confirm that the information had been appropriately understood and acted upon. If not, the duty radiologist contacted the referral physician by telephone. One year after implementing this strategy, we retrospectively evaluated 1-year worth of data for all the reports of CT, MRI, nuclear medicine and ultrasonography (April 2018 to March 2019).

Results: Three hundred and twenty-one reports were double starred (0.52% of 62,143 reports, 1.32 reports/day), and transmission of relevant information was incomplete in 23 cases (7.17%). Causes of incomplete transmission were (1) reports not being opened (n = 17), (2) relevant information on reports being overlooked (n = 5), and (3) the wrong report being opened (n = 1). Sixty-five reports contained triple stars (0.10%, 0.27 reports/day).

Conclusion: The proposed strategy may be effective in preventing communication errors in radiology reports with important findings requiring semi-emergency clinical action.
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http://dx.doi.org/10.1007/s11604-020-00944-2DOI Listing
July 2020

Diagnosis of bladder cancer using F-labeled α-methyl-phenylalanine tracers in a mouse model.

Ann Nucl Med 2020 May 6;34(5):329-336. Epub 2020 Mar 6.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, 371-8511, Japan.

Objective: Although 2-F-fluoro-2-deoxy-glucose (F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of primary/recurrent lesions in the bladder, mainly because of interference by the pooled radioactivity in the urine. Our previous study revealed promising properties of L- and D-2-F-α-methyl-phenylalanine (2-F-FAMP) as radiotracers; i.e., their rapid blood clearance and low renal accumulation. In the present study we evaluated the utility of L- and D-2-F-FAMP for imaging bladder cancer in a mouse model.

Methods: We used the human bladder cancer cell line HT1376 to prepare a bladder cancer xenograft model in mice bearing both orthotopic and subcutaneous tumors. Biodistribution and PET imaging studies were performed at 1 and 3 h after injection of L-2-F-FAMP or D-2-F-FAMP. F-FDG was used as a control.

Results: At 1 h after injection, greater accumulations of both L-2-F-FAMP and D-2-F-FAMP were observed in the orthotopic tumors compared to F-FDG. The orthotopic tumor-to-muscle ratio of D-2-F-FAMP was significantly higher than that of F-FDG (p < 0.01), because of the rapid blood clearance of D-2-F-FAMP. L-2-F-FAMP showed the highest subcutaneous tumor-to-muscle ratio (p < 0.01) due to its high subcutaneous tumor uptake. Compared to L-2-F-FAMP, D-2-F-FAMP exhibited faster clearance and lower kidney accumulation. In the PET imaging studies, L- and D-2-F-FAMP both clearly visualized the orthotopic bladder tumors at 1 h after injection.

Conclusion: Our study showed that L-2-F-FAMP and D-2-F-FAMP have the potential to detect bladder cancer.
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http://dx.doi.org/10.1007/s12149-020-01452-zDOI Listing
May 2020

A new brain CT reference line: the lower eyelid to the inner occipital base line closely parallels the Talairach-Tournoux line.

Acta Radiol Open 2020 Jan 27;9(1):2058460120902406. Epub 2020 Jan 27.

Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medicine, Gunma University, Gunma, Japan.

Background: There is no standardized brain computed tomography (CT) reference line that can be determined on both scout and reformatted sagittal CT images. Here, a tangential line from the anterior edge of the lower eyelid to the inner table of the occipital base (LEL/O line) appears nearly parallel to the Talairach-Tournoux (T/T) line, which shows a consistent intracranial anatomical relationship among subjects, and acts as a standard reference line for magnetic resonance (MR) imaging.

Purpose: To quantitatively validate the LEL/O line as a new standard brain CT reference line.

Material And Methods: We measured: angle 1 = the LEL/O line on scout images from the LEL/O line on parasagittal CT images (n=93); and angle 2 = the LEL/O line on scout images from the T/T line on high resolution midsagittal MR images (n=97). Angles in a clockwise direction were defined as positive and were expressed as mean±SD with the 95% confidence interval (CI) of the SD. Angle 2 was measured independently by two observers and intraclass correlation coefficients (ICCs) were calculated.

Results: Angle 1 was -0.4°±1.2° (95% CI of SD 1.1°-1.5°); angle 2 was -0.4°±2.0° (95% CI of SD, 1.8°-2.4°). The ICC in the angle 2 measurement was 0.780 (<0.001), which indicated high inter-observer reliability.

Conclusion: The LEL/O lines on scout and parasagittal CT images show practically the same gradient, and these LEL/O lines are almost parallel to the T/T line. Use of the LEL/O line either for direct scanning or reformation can minimize intra- and inter-subject variations on CT images and mismatch between CT and MR images.
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http://dx.doi.org/10.1177/2058460120902406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985971PMC
January 2020

Early detection of progressive disease using thyroglobulin doubling-time in metastatic differentiated thyroid carcinoma treated with radioactive iodine.

Nucl Med Commun 2020 Apr;41(4):350-355

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine.

Objective: Detectable serum thyroglobulin (Tg) in patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy indicates progression of the disease. Thyroglobulin doubling-time (TgDT) is a powerful prognostic predictor in patients with DTC. We aimed to evaluate the value of the dynamic TgDT for early detection of progressive disease (PD) in the patients of metastatic DTC with I radioactive iodine (RAI) therapy.

Methods: We retrospectively evaluated 21 patients undergoing RAI therapy with metastatic DTC. Patients were defined as PD or non-PD according to Response Evaluation Criteria in Solid Tumors 1.1. TgDT was calculated by Excel-based software using Tg values measured during routine follow-up. Whole data (WDT), initial four data (IDT) and recent four data (RDT) of TgDT after total thyroidectomy were calculated and compared.

Results: Among the 21 patients (10 men; median age, 62 years old; range, 33-80), 11 patients were classified into PD and 10 were into non-PD. The initial Tg after total thyroidectomy showed a significant difference between PD and non-PD patients (P = 0.013). Short WDT, IDT and RDT (less than one year) showed a high correlation with PD (P < 0.05). RDT showed the highest predictive value for PD (P < 0.001). All the 11 PD patients showed RDT less than one year before PD (median follow-up, 157 days; range, 88-252).

Conclusions: RDT is a powerful PD predictor in patients with metastatic DTC. Dynamic monitoring of RDT should be applied for the early detection of PD in clinic.
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http://dx.doi.org/10.1097/MNM.0000000000001154DOI Listing
April 2020

The extra miles on preventing nephrogenic systemic fibrosis.

Quant Imaging Med Surg 2019 Nov;9(11):1911-1913

Diagnostic Radiology and Nuclear Medicine Department, Gunma University Graduate School of Medicine, Japan.

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http://dx.doi.org/10.21037/qims.2019.09.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902147PMC
November 2019

Shoulder tenderness was associated with the inflammatory changes on magnetic resonance imaging in patients with rheumatoid arthritis.

Sci Rep 2019 12 20;9(1):19599. Epub 2019 Dec 20.

Department of Orthopaedic Surgery, Graduate School of Medicine, Gunma University, Gunma, Japan.

The aim of this study was to assess the association between the shoulder tenderness and the inflammatory changes on magnetic resonance imaging (MRI) in the rheumatoid shoulder. Forty-one shoulders of 41 patients with rheumatoid arthritis (RA) were examined. We evaluated synovitis, erosion and bone marrow edema, by counting the numbers of each positive site, and rotator cuff tears on shoulder MRI. The association between the shoulder tenderness and the MRI findings were statistically analyzed. Twenty-three of 41 patients had tenderness in the shoulder joints. There were 20 shoulders (48.8%) with rotator cuff tear, and no significant difference was observed in the prevalence of rotator cuff tear between the tenderness group and non-tenderness group (p = 0.080). There were no significant differences in the demographic data between these two groups. In MRI findings, we found significant difference for the synovitis (p = 0.001) and bone marrow edema (p = 0.021). Synovitis was strongly associated with the shoulder tenderness (OR: 3.996, 95% CI: 1.651-9.671). Synovitis was the factor most associated with shoulder tenderness.
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http://dx.doi.org/10.1038/s41598-019-55938-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925129PMC
December 2019

Differential and quantitative neuroimaging characteristics of inclusion body myositis.

J Clin Neurosci 2020 Feb 12;72:244-251. Epub 2019 Dec 12.

Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan. Electronic address:

In clinical settings, it is often difficult to distinguish inclusion body myositis (IBM) from other neuromuscular diseases. In order to clarify clinically useful characteristics for making the differential diagnosis of IBM, we performed clinical, epidemiological, and neuroimaging analyses in patients with various types of neuromuscular disorders. We enrolled 333 patients with myopathy and 12 patients with amyotrophic lateral sclerosis (ALS) who had been hospitalized in our department from January 1, 1979, to December 31, 2018. Among them, 18 patients with IBM, 16 patients with polymyositis (PM), and 12 patients with ALS who showed equivalent severity of muscle weakness in their lower limbs underwent the quantitative neuroimaging analysis using lower limb CT and clinical assessment. Patients with IBM exhibited significantly greater muscular degeneration in the rectus femoris, vastus, sartorius, adductor, anterior calf, and medial gastrocnemius muscles than those with PM or ALS. The ratio of the remaining muscle area of the quadriceps relative to that of the hamstrings and the duration from onset to CT imaging were negatively correlated in patients with IBM, indicating that the anterior thigh muscles were preferentially affected over the posterior muscles. Characteristic muscular degeneration in the lower limbs on CT imaging may aid for making the diagnosis of IBM.
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http://dx.doi.org/10.1016/j.jocn.2019.11.029DOI Listing
February 2020

Relationship Between Tumor Immune Markers and Fluorine-18-α-Methyltyrosine ([F]FAMT) Uptake in Patients with Lung Cancer.

Mol Imaging Biol 2020 08;22(4):1078-1086

Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan.

Purpose: 3-[F]Fluoro-α-methyl-L-tyrosine ([F]FAMT) is an amino acid positron emission tomography (PET) tracer specific for cancer detection by assessment of tumor amino acid metabolism. Little is known on whether or not the uptake of [F]FAMT within cancer cells is associated with the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody efficacy. We conducted a clinicopathological study to assess the expression of PD-L1 and the presence of tumor-infiltrating lymphocytes (TILs) in patients with non-small cell lung cancer (NSCLC) diagnosed by PET.

Procedures: A total of 75 patients with NSCLC who underwent [F]FAMT and 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) PET were enrolled in the study. Tumor specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), PD-L1 (using different antibody clones including E1L3N and 28-8), CD3, CD4, and CD8. The uptake of [F]FAMT was correlated with clinicopathological variables.

Results: High uptake of [F]FAMT was significantly associated with disease staging, initial treatment (surgical resection or chemotherapy), and the expression of PD-L1 (E1L3N). The value of the maximum standardized uptake value (SUV) for [F]FAMT was significantly correlated with PD-L1 (E1L3N) expression, Glut1, and the SUV for [F]FDG in patients with histological results of adenocarcinoma (AC) and advanced disease. A validation cohort for anti-PD-L1 using clone 28-8 showed a statistically significant correlation between SUV for [F]FAMT and the expression of PD-L1 (28-8) and between the expression of PD-L1 (E1L3N) and PD-L1 (28-8).

Conclusions: The uptake of [F]FAMT on PET imaging was significantly correlated with PD-L1 expression in NSCLC, especially in patients with AC and advanced disease.
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http://dx.doi.org/10.1007/s11307-019-01456-wDOI Listing
August 2020

Prognostic significance of semi-quantitative FDG-PET parameters in stage I non-small cell lung cancer treated with carbon-ion radiotherapy.

Eur J Nucl Med Mol Imaging 2020 05 22;47(5):1220-1227. Epub 2019 Nov 22.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.

Purpose: Prognostic significance of volumetric F-fluorodeoxyglucose (FDG) positron emission tomography/computer tomography (PET/CT) parameters in carbon-ion radiotherapy (C-ion RT) treated stage I non-small cell lung cancer, and need of histology-wise separate cut-off values for risk stratification were assessed.

Methods: Thirty-nine patients (29 men and 10 women, 71.9 ± 8.3 years) who underwent FDG PET/CT examinations before C-ion RT were retrospectively evaluated. FDG-PET parameters: standardized uptake values (SUVmax, SUVpeak, and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinicopathological variables were assessed for prognosis using Cox proportional hazards regression analysis. Mann-Whitney test compared medians of significant parameters between adenocarcinoma (AC) and squamous cell carcinoma (SCC), and Kaplan-Meier curves were plotted for median-based low- and high-risk groups.

Results: Median follow-up period was 44.8 months. 1/2/3-year overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 94.9/84.3/70.8, 82.1/69.2/58.4 and 97.3/85.7/82.3%. Multivariate analysis revealed age (hazard ratio, HR: 1.09; 95% confidence interval, CI: 1.0-1.19, p < 0.05) and MTV (HR 4.83, 95% CI 1.21-19.27, p < 0.03) predicted OS, and only MTV predicted PFS (HR 5.3, CI 1.32-21.35, p < 0.02) independently. Compared with AC, SCC had higher MTV (median, 6.625cm vs 0.2 cm, p < 0.01). Single MTV cut-off based on overall cohort was insignificant in SCC for PFS (p > 0.02); separate cut-offs of MTV, 0.2 cm for AC (p < 0.03) and 6.625 cm for SCC (p < 0.05) were relevant.

Conclusion: Among all FDG PET/CT parameters, only MTV beared prognostic ability for stage I NSCLC treated with C-ion RT, and its histological variation may need consideration for risk-adapted therapeutic management.
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http://dx.doi.org/10.1007/s00259-019-04585-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101295PMC
May 2020

Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer.

BMC Cancer 2019 Oct 24;19(1):1000. Epub 2019 Oct 24.

Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.

Backgrounds: Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels.

Methods: The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either In- or Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting.

Results: We found that tumors with high EGFR expression had significantly higher [In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors.

Conclusion: Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.
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http://dx.doi.org/10.1186/s12885-019-6238-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813975PMC
October 2019