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1.
World J Clin Cases ; 12(5): 931-941, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38414613

RESUMO

BACKGROUND: There are limited data on the use of glucose transport protein 1 (GLUT-1) expression as a biomarker for predicting lymph node metastasis in patients with colorectal cancer. GLUT-1 and GLUT-3, hexokinase (HK)-II, and hypoxia-induced factor (HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). AIM: To evaluate GLUT-1, GLUT-3, HK-II, and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT. METHODS: This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012. Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist, and the expressions of GLUT-1, GLUT-3, HK-II, and HIF-1 were determined using immunohistochemical staining. We analyzed the correlations among their expressions, various clinicopathological factors, and the maximum standardized uptake value (SUVmax) of PET/CT. RESULTS: GLUT-1 was found at the center or periphery of the tumors in 109 (64.5%) of the 169 patients. GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes, regardless of the biopsy site (tumor center, P < 0.001 and P = 0.012; tumor periphery, P = 0.030 and P = 0.010, respectively). GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT, respectively, for the detection of lymph node metastasis, regardless of the biopsy site. GLUT3, HK-II, and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes. CONCLUSION: GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes. Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

2.
PLoS One ; 19(1): e0296466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38165945

RESUMO

BACKGROUND: Lymphaticovenous anastomosis (LVA) is a promising microsurgical treatment for lower extremity lymphedema (LEL). Lymphoscintigraphy effectively assesses lower limb lymphatic systems before LVA, but its role in predicting the therapeutic outcomes of LVA is indeterminate. In this study we investigate the efficacy of preoperative lymphoscintigraphy using clinical findings to predict outcomes in gynecological cancer-related LEL patients who underwent LVA. METHODS: A retrospective review was conducted on consecutive gynecological cancer patients with LEL who had undergone LVA between June 2018 and June 2021. The therapeutic efficacy was assessed by measuring the change rate of the lower extremity lymphedema index (LELi) six months after surgery. Clinical data and lymphoscintigraphic findings were analyzed to assess therapeutic efficacy of LVA. RESULTS: Out of the 60 evaluated legs, 83.3% of the legs showed improved results after LVA. Univariable linear regression analysis revealed that higher preoperative LELi, and ovarian cancer were associated with superior LELi change rate (LC rate). Absence of dermal backflow (DBF) on lymphoscintigraphy was associated with inferior LC rate. Multivariable linear regression analysis identified ovarian cancer and higher preoperative LELi were independently correlated with favorable outcomes, while the absence of DBF was independently correlated with inferior outcomes. CONCLUSION: The results of this study emphasizes the effectiveness of preoperative lymphoscintigraphy, preoperative LELi, and primary malignancy as predictors of LVA outcomes in gynecological cancer-related LEL patients.


Assuntos
Vasos Linfáticos , Linfedema , Neoplasias Ovarianas , Humanos , Feminino , Linfocintigrafia , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/cirurgia , Resultado do Tratamento , Linfedema/diagnóstico por imagem , Linfedema/cirurgia , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/cirurgia , Anastomose Cirúrgica/métodos , Estudos Retrospectivos
3.
Radiat Oncol J ; 41(2): 89-97, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37403351

RESUMO

PURPOSE: We aimed to determine whether low-dose radiotherapy (LDRT) is effective in patients with Alzheimer disease (AD). MATERIALS AND METHODS: We included patients according to the following criteria: probable Alzheimer's dementia according to the New Diagnostic Criteria for Alzheimer's Disease; confirmation of amyloid plaque deposits on baseline amyloid positron emission tomography (PET); a Korean Mini-Mental State Examination 2nd edition (K-MMSE-2) score of 13-26; and a Global Clinical Dementia Rating (CDR) score of 0.5-2 points. LDRT was performed six times at 0.5 Gy each. Post-treatment cognitive function tests and PET-CT examinations were performed to evaluate efficacy. The medication for AD treatment was maintained throughout the study period. RESULTS: At 6 months after LDRT, neurological improvement was seen in 20% of patients. Patient #2 showed improvement in all domains of the Seoul Neuropsychological Screening Battery II (SNSB-II). Moreover, the K-MMSE-2 and Geriatric Depression Score-Short Form scores improved from 20 to 23 and from 8 to 2, respectively. For patient #3, the CDR score (sum of box score) improved from 1 (4.0) to 1 (3.5) at 3 months follow-up. Moreover, the Z scores for language and related functions, memory, and frontal executive function improved to -2.56, -1.86, and -1.32, respectively at the 6-month follow-up. Two patients complained of mild nausea and mild hair loss during LDRT, which improved after treatment. CONCLUSION: One of the five patients with AD treated with LDRT experienced a temporary improvement in SNSB-II. LDRT is tolerable in patients with AD. We are currently under follow-up and will conduct cognitive function tests after 12 months after LDRT. A large-scale randomized controlled trial with a longer follow-up period is warranted to determine the effect of LDRT on patients with AD.

4.
Clin Transl Sci ; 16(7): 1186-1196, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37038354

RESUMO

Although aptamers have shown excellent target specificity in preclinical and clinical studies either by themselves or as aptamer-drug conjugates, their in vivo tissue pharmacokinetic (PK) analysis is still problematic. We aimed to examine the utility of image-based positron emission tomography (PET) to evaluate in vivo tissue PK, target specificity, and applicability of oligonucleotides. For this, fluorine-18-labeled aptamers with erb-b2 receptor tyrosine kinase 2 (ERBB2)-specific binding were synthesized by base-pair hybridization using a complementary oligonucleotide platform. To investigate the PKs and properties of in vivo tissue, usefulness of in vivo PET imaging in the development of an oligonucleotide-based drug as an assessment tool was evaluated in normal and tumor xenografted mice. ERBB2-cODN-idT-APs-[18 F]F ([18 F]1), injected intravenously showed significant and rapid uptake in most tissues except for the initial brain and muscle; the uptake was highest in the heart, followed by kidneys, liver, lungs, gall bladder, spleen, and stomach. The main route of excretion was through the renal tract ~77.8%, whereas about 8.3% was through the biliary tract of the total dose. The estimated effective dose for an adult woman was 0.00189 mGy/MBq, which might be safe. ERBB2-positive tumor could be well visualized in the KPL4 xenograft animal model by in vivo PET imaging. Consequently, the distribution in each organ including ERBB2 expression could be well determined and quantified by PET with fluorine-18-labeled aptamers. In vivo PK parameters such as terminal half-life, time to maximum concentration, area under the curve, and maximum concentration, were also successfully estimated. These results suggest that image-based PET with radioisotope-labeled aptamers could be provide valuable information on properties of oligonucleotide-based drugs in drug discovery of targeted therapeutics against various diseases.


Assuntos
Neoplasias , Oligonucleotídeos , Humanos , Camundongos , Animais , Receptor ErbB-2 , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Modelos Animais de Doenças
5.
Clin Nucl Med ; 48(4): e160-e162, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727884

RESUMO

ABSTRACT: Abdominothoracic fistula is rarely observed but can be life-threatening. Pleuroperitoneal communication, known to occur in 1.6% of all patients who undergo continuous ambulatory peritoneal dialysis, is an uncommon but well-recognized complication. The most common symptoms are dyspnea and right-sided pleural effusion. A biliopleural fistula is well-described as a complication of radiofrequency ablation and transcatheter arterial chemoembolization of hepatic lesions. It is important to diagnose the cause of pleural effusion early for proper treatment because if the abdominothoracic fistula effusion amount is not large, appropriate diagnosis may be difficult. Here, we introduce 2 cases showing the usefulness of SPECT/CT in evaluating pleuroperitoneal and biliopleural fistulas.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Fístula , Neoplasias Hepáticas , Derrame Pleural , Humanos , Carcinoma Hepatocelular/complicações , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/complicações , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
6.
Clin Nucl Med ; 47(8): e562-e564, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35384903

RESUMO

ABSTRACT: An 11-year-old boy who presented with headache and progressive right-sided weakness exhibited cortical swelling in the parafalcine area of both frontoparietal high convexity and splenium portion of corpus callosum on brain MRI. This suggested the possibility of encephalopathy, but required differential diagnosis from brain tumor. 18 F-FET ( O -(2-[ 18 F]fluoroethyl)- l -tyrosine) PET/CT identified increased uptake along the parafalcine area of the frontoparietal lobes and the splenium portion of the corpus callosum. The relatively low target-to-background ratios were more indicative of inflammatory changes such as demyelinating disease. The patient recovered after empirical steroid and immunoglobulin treatment. Clinically, the patient was diagnosed with acute disseminated encephalomyelitis.


Assuntos
Neoplasias Encefálicas , Doenças Desmielinizantes , Neoplasias Encefálicas/patologia , Criança , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Tirosina
7.
Nucl Med Commun ; 42(12): 1396-1403, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34392298

RESUMO

OBJECTIVE: Typical clinical dosimetry models for trans-arterial radioembolization (TARE) assume uniform dose distribution in each tissue compartment. We performed simple voxel-based dosimetry using post-treatment 90Y PET following TARE with 90Y-resin microspheres and investigated its prognostic value in a pilot cohort. METHOD: Ten patients with 14 hepatocellular carcinoma lesions who underwent TARE with 90Y-resin microspheres were retrospectively included. The partition model-based expected target tumor dose (TDp) was calculated using a pretreatment 99mTc-macroaggregated albumin scan. From post-treatment 90Y-microsphere PET and voxel-wise S-value kernels, voxel-based dose maps were produced and the absorbed dose of each lesion (TDv) was calculated. Heterogeneity of intratumoral absorbed doses was assessed using the SD and coefficient of variation of voxel doses. The response of each lesion was determined based on contrast-enhanced MRI or CT, or both. Lesion responses were classified as local control success or failure. Prognostic values of dosimetry parameters and clinicopathological factors were evaluated in terms of progression-free survival (PFS) of each lesion. RESULTS: TDv was significantly different between local control success and failure groups, whereas tumor size, TDp and intratumoral dose heterogeneity were not. Univariate survival analysis identified serum aspartate transaminase level ≥40 IU/L, tumor size ≥66 mm and TDv <81 Gy as significant prognostic factors for PFS. However, only TDv was an independent predictive factor in the multivariate analysis (P = 0.022). There was a significant correlation between TDv and PFS (P = 0.009; r = 0.669). CONCLUSIONS: In TARE, voxel-based dose index TDv can be estimated on post-treatment 90Y PET using a simple method. TDv was a more effective prognostic factor for TARE than TDp and clinicopathologic factors in this pilot study. Further studies are warranted on the role of voxel-based dose and dose distribution in TARE.


Assuntos
Carcinoma Hepatocelular
8.
Medicine (Baltimore) ; 99(35): e21829, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871906

RESUMO

Imaging parameters including metabolic or textural parameters during F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are being used for evaluation of malignancy. However, their utility for prognosis prediction has not been thoroughly investigated. Here, we evaluated the prognosis prediction ability of imaging parameters from preoperative FDGPET/CT in operable pancreatic cancer patients.Sixty pancreatic cancer patients (male:female = 36:24, age = 67.2 ±â€Š10.5 years) who had undergone FDGPET/CT before the curative intent surgery were enrolled. Clinico-pathologic parameters, metabolic parameters from FDGPET/CT; maximal standard uptake value (SUVmax), glucose-incorporated SUVmax (GI-SUVmax), metabolic tumor volume, total-lesion glycolysis, and 53 textural parameters derived from imaging analysis software (MaZda version 4.6) were compared with overall survival.All the patients underwent curative resection. Mean and standard deviation of overall follow-up duration was 16.12 ±â€Š9.81months. Among them, 39 patients had died at 13.46 ±â€Š8.82 months after operation, whereas 21 patients survived with the follow-up duration of 18.56 ±â€Š9.97 months. In the univariate analysis, Tumor diameter ≥4 cm (P = .003), Preoperative Carbohydrate antigen 19-9 ≥37 U/mL (P = .034), number of metastatic lymph node (P = .048) and GI-SUVmax (P = .004) were significant parameters for decreased overall survival. Among the textural parameters, kurtosis3D (P = .052), and skewness3D (P = .064) were potentially significant predictors in the univariate analysis. However, in multivariate analysis only GI-SUVmax (P = .026) and combined operation (P = .001) were significant independent predictors of overall survival.The current research result indicates that metabolic parameter (GI-SUVmax) from FDGPET/CT, and combined operation could predict the overall survival of surgically resected pancreatic cancer patients. Other metabolic or textural imaging parameters were not significant predictors for overall survival of localized pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Antígenos Glicosídicos Associados a Tumores/análise , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Cuidados Pré-Operatórios , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 99(30): e21353, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791738

RESUMO

RATIONALE: A deep neck infection (DNI) with descending necrotizing mediastinitis (DNM) has great clinical importance because of its high morbidity and mortality, particularly when associated with predisposing underlying disease. With the expanding clinical use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), it may be necessary to perform FDG PET/CT for immediate diagnosis and treatment of DNM. To the best of our knowledge, this is the first case report of DNI with DNM diagnosed based on FDG PET/CT findings. PATIENT CONCERNS: A 65-year-old man who underwent chemotherapy for stage IV lung cancer complained of sore throat, fever, and mild pain in the right upper arm for 4 days before admission. DIAGNOSES: FDG PET/CT revealed retropharyngeal abscess with acute osteomyelitis of the vertebral bodies of C4 and C5 and DNM. In blood and sputum cultures, Klebsiella pneumoniae was isolated. DNI with DNM was diagnosed based on contrast-enhanced neck and chest CT. INTERVENTIONS AND OUTCOME: Because of his underlying condition, antibiotic therapy with ceftriaxone and ciprofloxacin was started. There was initial improvement, but the patient died after 2 weeks from sepsis and multiorgan failure. LESSONS: The findings of DNI with DNM on FDG PET/CT were as follows: as an acute infection, DNM showed more severe uptake relative to the average maximum standardized uptake value of brown fat or physiologic muscle; showed the prevertebral uptake pattern rather than the paravertebral uptake pattern of brown fat; and showed continuous patterns of hypermetabolic lesions from the retropharyngeal/parapharyngeal space to the thoracic prevertebral space.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Fluordesoxiglucose F18 , Mediastinite/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Carcinoma Pulmonar de Células não Pequenas , Evolução Fatal , Humanos , Neoplasias Pulmonares , Masculino
10.
Medicine (Baltimore) ; 98(39): e17378, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574888

RESUMO

RATIONALE: Pulmonary tuberculosis and lung adenocarcinoma are highly prevalent pulmonary diseases associated with high mortality. However, the coexistence of lung cancer and pulmonary tuberculosis is rare. Further, the morphological features of lung cancer with coexisting pulmonary tuberculosis are similar to that of lung cancer without pulmonary tuberculosis, even though the lesion is predominantly cavity. For these reasons, the diagnosis in patients with coexisting lung cancer and pulmonary tuberculosis could be delayed until the advanced stage, and therefore, prognosis in these patients is worse compared with that of lung cancer patients without coexisting pulmonary tuberculosis. Therefore, early diagnosis of the condition is essential for initiating timely and suitable treatment. PATIENT CONCERNS: A 67-year-old man was detected abnormal finding on chest CT performed outside the hospital during health screening without significant symptom. DIAGNOSES: Chest CT revealed a 3.2, irregular, enhancing cavitary mass in right lower lobe of lung and PET-CT revealed significant uptake of 18 FDG by the cavitary mass, which was suggestive of lung cancer. Pathology results confirmed a diagnosis of coexisting lung adenocarcinoma and tuberculosis. INTERVENTIONS AND OUTCOME: The patient underwent a right lower lobectomy. No significant complications occurred in a 24 month post-surgery follow-up period LESSONS:: Although rare, the coexistence of lung adenocarcinoma and tuberculosis within a single lesion can occur. Therefore, early diagnosis of such a lesion is essential to improve the prognosis in affected patients.


Assuntos
Adenocarcinoma de Pulmão/microbiologia , Neoplasias Pulmonares/microbiologia , Tuberculose Pulmonar/microbiologia , Idoso , Humanos , Pulmão/microbiologia , Masculino , Tuberculose Pulmonar/complicações
11.
Nucl Med Mol Imaging ; 53(3): 231-234, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31231444

RESUMO

A 45-year-old male visited our clinic due to right palmar anhidrosis and contralateral hyperhidrosis. Chest computed tomography (CT) showed a solitary pulmonary nodule with mediastinal lymph node enlargement, but a cause for atypical palmar anhidrosis was not identified. Subsequent fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed (PET/CT) revealed a localized pleural metastasis at the right apex with direct invasion of the paravertebral sympathetic chain. The pleural metastasis, which was not seen on chest CT, evoked ipsilateral anhidrosis independent of a mass effect or direct invasion by the primary lung tumor. 18F-FDG PET/CT can be helpful in identifying the cause of atypical symptoms in patient with small sized lung cancer.

12.
Eur J Nucl Med Mol Imaging ; 46(7): 1417-1427, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30941463

RESUMO

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic volumetric parameters as a quantitative index on pre-treatment 18F-FDG PET/CT in addition to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 103 consecutive patients with DLBCL and baseline FDG PET/CT were retrospectively evaluated. Quantitative metabolic parameters, including total metabolic tumour volume (TMTV) using a standardized uptake value (SUV) of ≥2.5 as the threshold, were estimated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values for the metabolic parameters. The relationships between study variables and patient survival were tested using Cox regression analysis. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: Median follow-up was 34 months. In patients with a low TMTV (<249 cm3), the 3-year progression free survival (PFS) rate was 83% and the overall survival (OS) rate was 92%, in contrast to 41% and 57%, respectively, in those with a high TMTV (≥249 cm3). In univariate analysis, a high TMTV and NCCN-IPI ≥4 were associated with inferior PFS and OS (P < 0.0001 for all), as was a high total lesion glycolysis (P = 0.004 and P = 0.005, respectively). In multivariate analysis, TMTV and NCCN-IPI were independent predictors of PFS (hazard ratio, HR, 3.11, 95% confidence interval, CI, 1.37-7.07, P = 0.007, and HR 3.42, 95% CI 1.36-8.59, P = 0.009, respectively) and OS (HR 3.41, 95% CI 1.24-9.38, P = 0.017, and HR 5.06, 95% CI 1.46-17.60, P = 0.014, respectively). TMTV was able to separate patients with a high-risk NCCN-IPI of ≥4 (n = 62) into two groups with significantly different outcomes; patients with low TMTV (n = 16) had a 3-year PFS rate of 75% and an OS rate of 88%, while those with a high TMTV had a 3-year PFS rate of 32% and an OS rate of 47% (χ2 = 7.92, P = 0.005, and χ2 = 8.26, P = 0.004, respectively). However, regardless of TMTV, patients with a low-risk NCCN-IPI of <4 (n = 41) had excellent outcomes (3-year PFS and OS rates of 85% and 95%, respectively). CONCLUSION: Pretreatment TMTV was an independent predictor of survival in patients with DLBCL. Importantly, TMTV had an additive prognostic value in patients with a high-risk NCCN-IPI. Thus, the combination of baseline TMTV with NCCN-IPI may improve the prognostication and may be helpful guide the decision for intensive therapy and clinical trials, especially in DLBCL patients with a high-risk NCCN-IPI.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Carga Tumoral , Adulto Jovem
13.
Cancer Res ; 79(4): 795-806, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30610087

RESUMO

Tumor hypoxia and aerobic glycolysis are well-known resistance factors for anticancer therapies. Here, we demonstrate that tumor-associated macrophages (TAM) enhance tumor hypoxia and aerobic glycolysis in mice subcutaneous tumors and in patients with non-small cell lung cancer (NSCLC). We found a strong correlation between CD68 TAM immunostaining and PET 18fluoro-deoxyglucose (FDG) uptake in 98 matched tumors of patients with NSCLC. We also observed a significant correlation between CD68 and glycolytic gene signatures in 513 patients with NSCLC from The Cancer Genome Atlas database. TAM secreted TNFα to promote tumor cell glycolysis, whereas increased AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in TAM facilitated tumor hypoxia. Depletion of TAM by clodronate was sufficient to abrogate aerobic glycolysis and tumor hypoxia, thereby improving tumor response to anticancer therapies. TAM depletion led to a significant increase in programmed death-ligand 1 (PD-L1) expression in aerobic cancer cells as well as T-cell infiltration in tumors, resulting in antitumor efficacy by PD-L1 antibodies, which were otherwise completely ineffective. These data suggest that TAM can significantly alter tumor metabolism, further complicating tumor response to anticancer therapies, including immunotherapy. SIGNIFICANCE: These findings show that tumor-associated macrophages can significantly modulate tumor metabolism, hindering the efficacy of anticancer therapies, including anti-PD-L1 immunotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Glicólise , Neoplasias Pulmonares/patologia , Macrófagos/imunologia , Hipóxia Tumoral/imunologia , Animais , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Prognóstico , Linfócitos T/imunologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/metabolismo
14.
Cardiovasc Intervent Radiol ; 40(10): 1624-1630, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28500460

RESUMO

PURPOSE: To address the feasibility of prophylactic temporary occlusion of the cystic artery using a detachable coil during 90Y radioembolization. MATERIALS AND METHODS: From January 2012 to October 2016, nine patients underwent temporary occlusion of the cystic artery during 90Y radioembolization. Based on the planning hepatic angiography, a detachable coil was deployed into the cystic artery, which arose from a more distal level (e.g., right anterior hepatic artery) than its usual origin, but the proximal 1 cm was left inside the microcatheter. 90Y microspheres were infused proximal to the cystic artery where the 99mTc-MAA had been infused, and then the coil was retrieved. Afterward, the patients underwent PET/CT imaging. Medical records were reviewed, and the differences in the uptake of 99mTc-MAA and 90Y microspheres in the gallbladder were evaluated using Wilcoxon's signed-rank test. RESULTS: Temporary placement of a detachable coil was feasible in all cases. On the angiograms obtained after detachable coil placement, the distal cystic artery and gallbladder were partially identifiable in eight of the nine (88.8%) patients, but fully restored after the removal of the coils in all cases. The proportional uptake of 99mTc-MAA (mean, 4.35%) and 90Y (mean, 0.90%) in the gallbladder was significantly different due to the temporary occlusion of the cystic artery (p = 0.004). No clinical complications were identified for three months after the procedure. CONCLUSION: Temporary occlusion of the cystic artery using a detachable coil appeared to be feasible and effective in reducing 90Y uptake in the gallbladder.


Assuntos
Braquiterapia/instrumentação , Braquiterapia/métodos , Vesícula Biliar/irrigação sanguínea , Oclusão Terapêutica/instrumentação , Oclusão Terapêutica/métodos , Radioisótopos de Ítrio/uso terapêutico , Idoso , Estudos de Viabilidade , Feminino , Vesícula Biliar/diagnóstico por imagem , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Resultado do Tratamento
15.
Nucl Med Mol Imaging ; 49(4): 291-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26550048

RESUMO

PURPOSE: C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG. METHODS: A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNRmax, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNRmax, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS). RESULTS: Median PFS of all patients was 7.9 months (range 1.0-53.8 months). In univariate analysis, MTV (cutoff 35 cm(3)) was a significant prognostic factor for PFS (P = 0.01), whereas TNRmax (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03). CONCLUSION: MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNRmax is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.

16.
Nucl Med Mol Imaging ; 49(4): 321-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26550053

RESUMO

Primary angiosarcoma of the bone (PAB) is a rare and fatal high-grade malignant vascular bone tumor. We report a rare case of multicentric PAB mimicking bone metastasis in a 59-year-old female patient with a history of sigmoid colon cancer. This patient complained of lower back and pelvic pain and presented with multiple osteolytic bone lesions on plain radiography and pelvic computed tomography. First, bone metastasis of sigmoid colon cancer was suspected. However, on the (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) scan, the patient presented unusual multiple hypermetabolic osteolytic bone lesions involving contiguous bones of the lower half of the body. After bone biopsy, these lesions were confirmed to be multicentric PAB. To the best of our knowledge, this is the first case report of an (18)F-FDG PET/CT scan in a patient with multicentric primary bone angiosarcoma.

17.
Sci Rep ; 5: 15636, 2015 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-26497063

RESUMO

Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with (99m)Tc-HMPAO under physiologic conditions and monitored in vivo distribution of (99m)Tc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with (99m)Tc-HMPAO for 1 hr incubation, followed by removal of free (99m)Tc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with (99m)Tc-HMPAO, the radiochemical purity of (99m)Tc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in (99m)Tc-HMPAO-ENVs. (99m)Tc-HMPAO-ENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with (99m)Tc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with (99m)Tc-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.


Assuntos
Exossomos/química , Compostos Radiofarmacêuticos/química , Coloração e Rotulagem/métodos , Tecnécio Tc 99m Exametazima/química , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Linhagem Celular , Portadores de Fármacos/química , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos BALB C
18.
Nucl Med Mol Imaging ; 47(3): 188-95, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24900106

RESUMO

PURPOSE: Basal/acetazolamide stress (99m)Tc-HMPAO single-photon emission computed tomography (SPECT) has been widely used for evaluation of hemodynamics; however, qualitative and subjective visual assessment of cerebrovascular reserve (CVR) has been performed in clinical settings. The aim of this study was to generate parametric CVR images and evaluate its feasibility of quantification. METHODS: Basal/acetazolamide stress (99m)Tc-HMPAO SPECT data from 17 patients who underwent bypass surgery or percutaneous transluminal angioplasty were used. Spatial normalization was performed and parametric CVR images were generated using relative CVR (rCVR) of each voxel proportional to CVR of the whole brain. Binary parametric maps to show area of relatively reduced CVR were generated also using threshold of rCVR < 90 %. We calculated rCVR of internal carotid artery (ICA) using the parametric CVR images and probabilistic maps for ICA territory. Pre- and postprocedural parametric CVR images were obtained and quantitative rCVRs were compared. The rCVRs were evaluated according to visual grades for regional decreased CVR. RESULTS: Postprocedural rCVR obtained from parametric CVR images increased significantly from preprocedural rCVR. The rCVR was significantly correlated with visual grades of reduced CVR for each side of ICA territories. CONCLUSIONS: We generated parametric CVR images for basal/acetazolamide stress (99m)Tc-HMPAO SPECT. As a quantitative measurement, rCVR obtained from the parametric image was feasibly assessed hemodynamic abnormalities with preserved anatomical information.

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