RESUMEN
BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative recurrence of hepatocellular carcinoma (HCC), even in early-stage HCC. In small HCC ≤ 3 cm, treatment options include anatomical resection or non-anatomical resection, and MVI has a major effect on treatment decisions. We aimed to identify the predictors of MVI in small HCC ≤ 3 cm. METHODS: We retrospectively studied 129 patients with very early or early-stage HCC ≤ 3 cm who had undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography and subsequent hepatic resection from January 2016 to August 2023. These patients were divided into the derivation cohort (n = 86) and validation cohort (n = 43). We examined the risk factors for MVI using logistic regression analysis, and established a predictive scoring system in the derivation cohort. We evaluated the accuracy of our scoring system in the validation cohort. RESULTS: In the derivation cohort, a Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), prothrombin induced by vitamin K deficiency or antagonist-II (PIVKA-II), and metabolic tumor volume (MTV) were independent predictors of MVI. We established the scoring system using these three factors. In the validation test, there were no MVI-positive cases with a score of 0 and 1, and all cases were MVI-positive with a score of 4. Moreover, with a score ≥ 2, the sensitivity, specificity, and accuracy of our scoring system were 100%, 71.4%, and 81.4%, respectively. CONCLUSIONS: Our scoring system can accurately predict MVI in small HCC ≤ 3 cm, and could contribute to establishing an appropriate treatment strategy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Invasividad Neoplásica , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismo , Microvasos/patología , Protrombina , Factores de Riesgo , Precursores de Proteínas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia/patología , Biomarcadores , Biomarcadores de Tumor/análisis , Hepatectomía , Carga TumoralRESUMEN
BACKGROUND: Preoperative differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is important because these tumors require different surgical strategies. This study investigated the usefulness of dual isotope, iodine-123-labeled N-isopropyl-p-iodo-amphetamine (123I-IMP) and thallium-201 chloride single-photon emission computed tomography (201Tl SPECT) for the differential diagnosis. METHODS: Twenty-five PCNSL patients and 27 GBM patients who underwent dual isotope imaging, 123I-IMP and 201Tl SPECT, are included. Tumor-to-normal (T/N) ratio was calculated from the ratio of maximum tracer counts in the lesion to the mean counts in the contralateral cerebral cortex. The mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin, respectively) on magnetic resonance imaging were also analyzed. RESULTS: Delayed phase 123I-IMP SPECT was the most useful imaging examination for the differentiation between PCNSL and GBM compared with early phase 123I-IMP SPECT, early and delayed phase 201Tl SPECT, ADCmean, and ADCmin. However, the median T/N ratios of PCNSL and GBM were 1.32 and 0.83, respectively, in the delayed phase 123I-IMP SPECT. On the other hand, the median T/N ratios of PCNSL and GBM were 3.10 and 2.34, respectively, in the delayed phase 201Tl SPECT, with excellent tumor detection. CONCLUSION: Delayed phase 123I-IMP SPECT could differentiate between PCNSL and GBM with high accuracy, but T/N ratio was low and tumor detection was poor. 201Tl SPECT was useful for estimation of the malignancy and localization of the tumors with high T/N ratio. Dual isotope 123I-IMP and 201Tl SPECT was useful for the preoperative diagnosis of PCNSL and GBM.
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Neoplasias Encefálicas , Glioblastoma , Linfoma , Humanos , Neoplasias Encefálicas/patología , Sistema Nervioso Central/patología , Diagnóstico Diferencial , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Radioisótopos de Yodo , Linfoma/diagnóstico por imagen , Linfoma/patología , Radiofármacos , Radioisótopos de Talio , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Tumor invasion is the most significant prognostic factor in ampullary cancer and is thus a crucial factor in decision making for treatment. Endoscopic ultrasound can be performed to evaluate tumor invasion, but its diagnostic accuracy varies depending on the endoscopist. This study aimed to assess the usefulness of fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperatively predicting tumor invasion in ampullary cancer. METHODS: We retrospectively evaluated 44 patients with ampullary cancer (adenoma, n = 6; adenocarcinoma, n = 38) who underwent surgical resection. The SUVmax of the ampullary tumor site was assessed using FDG-PET, and the correlation among tumor invasion, lymph node metastasis, and other clinicopathological factors was evaluated. RESULTS: The SUVmax of the ampullary tumor site gradually increased depending on the extent of tumor invasion (p = 0.0075). Moreover, the SUVmax was significantly different between ≤T1a and ≥T1b, which is an indication for endoscopic papillectomy or surgical resection (p = 0.0015). The SUVmax of the ampullary section was significantly correlated with lymph node metastasis (p = 0.035). CONCLUSION: The SUVmax of the ampullary tumor site is correlated with tumor invasion and lymph node metastasis in ampullary cancer. Thus, FDG-PET can be a useful modality for preoperative staging and treatment strategy.
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Ampolla Hepatopancreática/diagnóstico por imagen , Neoplasias del Conducto Colédoco/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Radiofármacos , Estudios RetrospectivosRESUMEN
BACKGROUND: Peristomal pyoderma gangrenosum (PPG) presents multiple challenges for healthcare providers. The diagnosis of PPG may be delayed, and it may be mistaken for an irritant dermatitis or an infection. Patients with ostomies secondary to inflammatory bowel disease (IBD) may experience PPG. Issues related to PPG include difficulty maintaining a seal of the ostomy pouching system and preventing contamination of the painful, necrotic ulcerations characteristic of this condition. Treatment focuses on the appropriate assessment of the ulcers, successful pouch application, and proper management of IBD through a collaborative effort of both dermatologists and certified WOC nurses (CWOCN). CASES: We treated 3 patients diagnosed with Crohn's disease (CD) who developed refractory PPG. All 3 were treated with a topical steroid lotion, prednisone, and adalimumab or a combination of these agents. Ostomy products and application were tailored to prevent leakage and protect areas of ulceration. All ulcers were healed within 6 months of our initial consultation. CONCLUSION: We successfully managed 3 patients with CD and PPG with appropriate ostomy care, including revision of the ostomy pouching techniques, topical steroid treatment, and treatment based on assessment of ulcer status by the dermatologist and the WOC nurse.
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Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Glucocorticoides/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Estomía/efectos adversos , Piodermia Gangrenosa/tratamiento farmacológico , Esteroides/uso terapéutico , Estomas Quirúrgicos/efectos adversos , Adalimumab/administración & dosificación , Administración Tópica , Adulto , Anciano de 80 o más Años , Antiinflamatorios/administración & dosificación , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Femenino , Glucocorticoides/administración & dosificación , Humanos , Complicaciones Posoperatorias , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Piodermia Gangrenosa/diagnóstico , Esteroides/administración & dosificación , Resultado del TratamientoRESUMEN
The relationship between the local immune status and cancer metabolism regarding 18 F-FDG and 18 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 18 F-FDG PET and 18 F-FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD-1), CD8, Ki-67, CD34, GLUT1 (18 F-FDG transporter) and LAT1 (18 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 18 F-FDG was significantly higher in high PD-L1 cases than in low PD-L1 cases (P = 0.009). SUVmax of 18 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 18 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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Biomarcadores de Tumor/análisis , Neoplasias Esofágicas/inmunología , Carcinoma de Células Escamosas de Esófago/inmunología , Tomografía de Emisión de Positrones/métodos , Adulto , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , alfa-MetiltirosinaRESUMEN
BACKGROUND: Lately, immune checkpoint proteins, such as programmed death 1 (PD-1) and its ligand-1 (PD-L1), have garnered attention as a new target in oral squamous cell carcinoma (OSCC). Reportedly, fluoro-D-glucose (FDG)-uptake alteration by anti-PD-1 antibody treatment depicts the response in patients with lung cancer. This study aims to elucidate the correlations between tumour immune status, clinicopathological factors, 18F-FDG-uptake and cold tumour phenotypes as low PD-L1 expression/low CD8+tumour-infiltrating lymphocytes (TILs) in OSCC. METHODS: We performed immunohistochemical analysis of PD-L1, hypoxia-inducible factor 1 A (HIF-1A), glucose transporter type 1 (GLUT1), CD8, E-cadherin and Ki-67 on 59 operable OSCC samples. We assessed the correlations between these factors and preoperative 18F-FDG-uptake, clinicopathological characteristics and prognosis. RESULTS: Low expression of PD-L1 in OSCC correlated with cancer aggressiveness, poor prognosis, high 18F-FDG-uptake with HIF-1A/GLUT1 and low E-cadherin expression and low CD8. Cold tumour phenotypes as low PD-L1 tumour cells and low stromal CD8 correlated with the poor prognosis, high 18F-FDG-uptake and E-cadherin suppression. Furthermore, the high level of preoperative 18F-FDG-uptake in OSCC was an independent predictor of the cold tumour immune status. CONCLUSIONS: 18F-FDG-uptake is an independent predictor of cold tumour in OSCC. 18F-FDG-PET imaging could be a promising diagnostic tool to estimate tumour immune status.
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Biomarcadores de Tumor/análisis , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Anciano , Antígeno B7-H1/biosíntesis , Linfocitos T CD8-positivos/inmunología , Resistencia a Antineoplásicos/inmunología , Femenino , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/patología , Humanos , Inhibidores de Puntos de Control Inmunológico , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
PURPOSE: Prognostic significance of volumetric 18F-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, 6.625cm3 vs 0.2 cm3, 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 cm3 for AC (p < 0.03) and 6.625 cm3 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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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carbono , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Estudios Retrospectivos , Carga TumoralRESUMEN
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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Imagen de Difusión por Resonancia Magnética/métodos , Metástasis Linfática/diagnóstico por imagen , Tumores Neuroendocrinos/diagnóstico por imagen , Pancreatectomía/efectos adversos , Neoplasias Pancreáticas/cirugía , Cuidados Preoperatorios/métodos , Adulto , Anciano , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Liver resection is the most effective procedure for colorectal cancer liver metastasis (CRLM); however, early recurrence is an important problem that affects the postoperative prognoses of patients with CRLM. We previously suggested a therapeutic algorithm for CRLM using fluorodeoxyglucose-positron emission tomography (FDG-PET) and revealed the applicability of FDG-PET in predicting the prognosis after liver resection of CRLM. In this study, we assessed the correlation between FDG-PET and biological viability such as proliferation or metabolic activity. METHODS: We retrospectively evaluated 61 patients who underwent hepatectomy for CRLM. We assessed hypoxia inducible factor-1α (HIF-1α), pyruvate kinase isozyme M2 (PKM2), glucose transporter 1 (GLUT1), and Ki-67 expression via immunohistochemistry and evaluated the correlation between standardized uptake value (SUV) and these factors. RESULTS: High HIF-1α, PKM2, and GLUT1 expression were positively correlated with high SUV expression (P = 0.0444, 0.0296, and 0.0245, respectively). Ki-67 and SUV were also positively correlated (P = 0.00164). HIF-1α expression and PKM2 expression were significantly correlated (P = 0.0430), and PKM2 expression and GLUT1 expression were extremely significantly correlated (P < 0.0001). CONCLUSION: SUV reflected tumor proliferation or metabolic factors in CRLM. FDG-PET could be a useful modality for assessing tumor viability and may provide useful information regarding the appropriate treatment strategy for CRLM.
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Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Portadoras/metabolismo , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Transportador de Glucosa de Tipo 1/metabolismo , Hepatectomía , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Radiofármacos/farmacocinética , Estudios Retrospectivos , Hormonas Tiroideas/metabolismo , Proteínas de Unión a Hormona TiroideRESUMEN
L-2-[18 F]fluoro-alpha-methylphenylalanine (2-[18 F]FAMP) is a promising amino acid tracer for positron emission tomography (PET) imaging, yet the low production yield of direct electrophilic radiofluorination with [18 F]F2 necessitates further optimization of the radiolabeling process. This paper describes a two-step preparation method for L-2-[18 F]fluoro-alpha-methylphenylalanine (2-[18 F]FAMP) starting from [18 F]fluoride. The (Mesityl)(L-alpha-methylphenylalanine)-2-iodonium tetrafluoroborate precursors with various protecting groups were prepared. The copper-mediated 18 F-fluorination of the iodonium salt precursors successfully produced 2-[18 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)2 . Subsequent deprotection with 57% hydrogen iodide produced 2-[18 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-[18 F]FAMP showed comparable biodistribution profiles in normal mice with that of the carrier-added 2-[18 F]FAMP. These results indicate that usefulness of copper mediated 18 F-fluorination for the production of 2-[18 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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Compuestos de Bifenilo/química , Cobre/química , Radioisótopos de Flúor/química , Halogenación , Compuestos Onio/química , Fenilalanina/química , Fenilalanina/síntesis química , Catálisis , Técnicas de Química Sintética , RadioquímicaRESUMEN
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 111In- or 64Cu-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 [111In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [111In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [64Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [64Cu]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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Antineoplásicos Inmunológicos/metabolismo , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cetuximab/metabolismo , Cetuximab/uso terapéutico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Animales , Antineoplásicos Inmunológicos/química , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Cetuximab/química , Radioisótopos de Cobre/química , Radioisótopos de Cobre/metabolismo , Receptores ErbB/metabolismo , Femenino , Compuestos Heterocíclicos con 1 Anillo/química , Compuestos Heterocíclicos con 1 Anillo/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Radiofármacos/química , Radiofármacos/metabolismo , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Positron emission tomography (PET) imaging with 18F-labeled α-methyl-substituted amino acids exerts significant influence on differential diagnosis of malignant tumors and tumor-like lesions. Exclusive uptake via L-type amino acid transporter 1 (LAT1), a tumor-specific transporter, accounts for their excellent tumor specificity and low background accumulation. However, further refinement and optimization in their tumor accumulation and pharmacokinetics are sorely needed. To address these issues, we newly designed 18F-labeled α-methyl-phenylalanine (18F-FAMP) regioisomers (2-, 3-, or 4-18F-FAMP) and stereoisomers (L- or D-form), and we comprehensively evaluated their potential as tumor-imaging agents. 18F-FAMPs were prepared from α-methyl phenylalanine by electrophilic radiofluorination and purified by reversed-phase HPLC. In biodistribution studies on normal mice, L-2-18F-FAMP and the three D-18F-FAMPs showed faster blood clearance and lower renal accumulation than L-3-18F-FAMP or L-4-18F-FAMP. In LS180 human colorectal cancer cell line xenograft mice, L-2-18F-FAMP exhibited significantly higher tumor accumulation than the D-18F-FAMPs or a clinically relevant tracer, L-3-18F-α-methyl-tyrosine (18F-FAMT) (p < 0.05). The renal accumulation levels of L-2-18F-FAMP were significantly lower than that of 18F-FAMT (p < 0.01). LAT-1 specificity of L-2-18F-FAMP was validated in the cellular uptake studies. The PET imaging with L-2-18F-FAMP clearly visualized the tumor as early as 1 h after injection, and the high tumor accumulation level was retained for 3 h. These findings suggest that L-2-18F-FAMP constitutes a potential PET tracer for tumor-specific imaging.
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Radioisótopos de Flúor , Neoplasias/diagnóstico por imagen , Fenilalanina/análogos & derivados , Radiofármacos/farmacocinética , Animales , Línea Celular Tumoral , Diagnóstico Diferencial , Humanos , Inyecciones Intravenosas , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Masculino , Ratones , Neoplasias/patología , Fenilalanina/administración & dosificación , Fenilalanina/química , Fenilalanina/farmacocinética , Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación , Radiofármacos/química , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Patients with chronic kidney disease (CKD) have an increased risk of adverse cardiovascular/cerebrovascular events. The aim of this study is to clarify whether stress myocardial perfusion single-photon emission computed tomography (SPECT) could predict cardiovascular/cerebrovascular events. In the Gunma-CKD SPECT Study, a multicenter prospective cohort trial, 311 patients with CKD (estimated glomerular filtration rate < 60 min/mL/1.73 m2) including 50 patients on hemodialysis underwent stress 99mTc-tetrofosmin SPECT for suspected ischemic heart disease and were followed for 2 years. The primary endpoint was the occurrence of cardiac death (CD), while the secondary endpoint was major adverse cardiovascular/cerebrovascular and renal events (MACCRE). MACCRE occurred in 91 out of 286 patients (CD in 13 and other MACCRE in 78 patients). According to a multivariate Cox analysis, hemoglobin (Hb) and end-systolic volume (ESV) were associated with CD (p < 0.05), while the summed difference score, diabetes mellitus (DM), and Hb were associated with MACCRE (p < 0.05). Kaplan-Meier analysis showed that the CD-free rate was higher in patients with ESV < 105 mL (log-rank, p = 0.0013), Hb > 12 g (log-rank, p = 0.0036), and a summed stress score < 6 (log-rank, p = 0.0058). The MACCRE-free rate was higher in patients with SDS = 0 (log-rank, p = 0.0097), without DM (log-rank, p = 0.0091), and with Hb > 12 g (log-rank, p = 0.0023). Myocardial perfusion SPECT parameters as well as renal anemia and DM can be reliable prognostic markers in patients with CKD including hemodialysis.
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Enfermedades Cardiovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/diagnóstico por imagen , Imagen de Perfusión Miocárdica , Insuficiencia Renal Crónica/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Enfermedades Cardiovasculares/complicaciones , Trastornos Cerebrovasculares/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Factores de RiesgoRESUMEN
BACKGROUND: Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether 18F-FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase. METHODS: Twenty-four patients were enrolled in this study. 18F-FDG-PET/CT was carried out before and 1 month after nivolumab therapy. SUVmax, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were calculated. Immunohistochemical analysis of PD-L1 expression and tumour-infiltrating lymphocytes was conducted. RESULTS: Among all patients, a partial metabolic response to nivolumab was observed in 29% on SUVmax, 25% on MTV, and 33% on TLG, whereas seven (29%) patients achieved a partial response (PR) based on RECIST v1.1. The predictive probability of PR (100% vs. 29%, p = 0.021) and progressive disease (100% vs. 22.2%, p = 0.002) at 1 month after nivolumab initiation was significantly higher in 18F-FDG on PET/CT than in CT scans. Multivariate analysis confirmed that 18F-FDG uptake after administration of nivolumab was an independent prognostic factor. PD-L1 expression and nivolumab plasma concentration could not precisely predict the early therapeutic efficacy of nivolumab. CONCLUSION: Metabolic response by 18F-FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Nivolumab , Valor Predictivo de las Pruebas , RadiofármacosAsunto(s)
Enfermedad de Crohn , Histiocitosis de Células de Langerhans , Humanos , Adalimumab/efectos adversos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Histiocitosis de Células de Langerhans/inducido químicamente , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/tratamiento farmacológicoRESUMEN
BACKGROUND: L-[3-18F]-α-methyltyrosine (18F-FAMT) solely accumulates in tumor cells via an amino acid transport system. This selective uptake pattern results in a very high tumor-to-background ratio, enabling clear delineation of the tumor. The purpose of the present study was to assess the significance of 18F-FAMT PET, which shows little nonspecific uptake compared to 18F-flourodeoxyglucose position emission tomography (FDG PET) in esophageal cancer patients. METHODOLOGY: PET-CT studies with 18F-FAMT and 18F-FDG were performed as part of pretreatment work-up in 82 patients with histologically confirmed esophageal cancer. We evaluated nonspecific uptakes of 18F-FDG and 18F-FAMT PET. RESULTS: The nonspecific uptake of 18F-FAMT PET was lower than that of 18F-FDG PET (p = 0.282). In the operation group, 26.1% demonstrated nonspecific uptake in 18F-FDG PET, whereas only 2.38% (1 case) demonstrated nonspecific uptake in 18F-FAMT PET (p = 0.433). In the inoperable group, 47.5% showed nonspecific uptake in 18F-FDG PET, whereas 5.0% showed nonspecific uptake in 18F-FAMT PET (p = 0.079). CONCLUSION: A crucial point for the diagnostic value of PET is distinguishing specific and nonspecific uptake. 18F-FAMT-PET is a very superior modality with regard to the lower rate of nonspecific uptake in esophageal cancer.
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Neoplasias Esofágicas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Radiofármacos , alfa-Metiltirosina , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: This study aimed to determine the prognostic value of positron emission tomography (PET) metabolic parameters-namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion retention (TLR)-on fluorine-18 (18F) fluorodeoxyglucose (FDG) and L- [3-18F]-α-methyltyrosine (18F-FAMT) PET/CT in patients with non-small-cell lung cancer (NSCLC). METHODS: The study group comprised 112 NSCLC patients who underwent 18F-FDG and 18F-FAMT PET/CT prior to any therapy. The MTV, TLG, TLR, and maximum standardized uptake value (SUVmax) of the primary tumors were determined. Automatic MTV measurement was performed using PET volume computer assisted reading software. (GE Healthcare). Cox proportional hazards models were built to assess the prognostic value of MTV, TLG (for 18F-FDG), TLR (for 18F-FAMT), SUVmax, T stage, N stage, M stage, clinical stage, age, sex, tumor histological subtype, and treatment method (surgery or other therapy) on overall survival (OS). RESULTS: Higher TNM, higher clinical stage, inoperable status, and higher values for all PET parameters (both 18F-FAMT and 18F-FDG PET) were significantly associated (P < 0.05) with shorter OS. Multivariate analysis revealed that a higher MTV of 18F-FAMT (hazard ratio [HR]: 2.88, CI: 1.63-5.09, P < 0.01) and advanced clinical stage (HR: 5.36, CI: 1.88-15.34, P < 0.01) were significant predictors of shorter OS. CONCLUSIONS: MTV of 18F-FAMT is of prognostic value for OS in NSCLC cases and can help guide decision-making during patient management.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Radioisótopos de Flúor/química , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , alfa-Metiltirosina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de Supervivencia , Carga Tumoral , alfa-Metiltirosina/químicaRESUMEN
The lack of isolation ward throughout Japan has long been limiting the 131I radioactive iodine (RAI) ablation for differentiated thyroid cancer (DTC) cases. The 30 mCi RAI ablation was only recently permitted for outpatient basis. However, no patient selection tool nor response predictor has been proposed. This study evaluated factors to find response predictor and determinant for the suitable patients. The retrospective study reviewed 47 eligible non-metastatic papillary DTC patients whose had first 30 mCi RAI ablation after total thyroidectomy. Age, gender, clinical stage, risk category, and pre-ablation serum thyroglobulin (Tg) level were among covariates analyzed to determine the patient selection factors; while the thyroid bed uptake on initial whole body scan (WBS) was later also included in determining RAI ablation response. Thirteen (28%) patients had a low risk (T1-2) while 23 (49%) and 11 (23%) had an intermediate (T3) or high risk (T4), respectively. Twenty-five patients were responders, and 22 were non-responders. All factors were similar between responders and non-responders except pre-ablation serum Tg level (p < 0.001). In multivariate analysis, pre-ablation serum Tg level was the only significant factor for both patient selection (odd ratio (OR) = 1.52, 95% confidence interval (CI) = 1.13-2.06) and response predictor (OR = 1.48; 95% CI = 1.12-1.95). With the cut-off of 5.4 ng/mL, pre-ablation serum Tg level predicts RAI ablation response with 92% specificity and 73% sensitivity. Pre-ablation serum Tg level may help patient selection and predict the response to outpatient 30 mCi RAI ablation among post total thyroidectomy non-metastatic DTC patients.
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Carcinoma Papilar/radioterapia , Radioisótopos de Yodo/uso terapéutico , Selección de Paciente , Neoplasias de la Tiroides/radioterapia , Adulto , Anciano , Carcinoma Papilar/cirugía , Terapia Combinada , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
BACKGROUND: Exercise therapy is one of the recognized treatment methods for knee osteoarthritis (KOA). One such exercise technique, straight leg raising (SLR), is widely known as a home exercise method for strengthening the quadriceps femoris muscle. However, whether this exercise truly strengthens the quadriceps is not known. The objective of the present study was to investigate which lower limb muscle is stimulated and shows increased activity with SLR. METHODS: A total of 14 lower limbs in seven healthy adult male volunteers (mean age: 31.3 ± 2.2 years) were investigated. Participants were asked to perform SLR and subsequently underwent FDG-PET/CT examination for evaluation of the muscles of the entire lower limb. The maximum standardized uptake value (SUVmax) of each muscle (iliacus, psoas major, gluteus maximus, gluteus medius, gluteus minimus, vastus medialis, vastus intermedius, vastus lateralis, rectus femoris, biceps femoris, semimembranosus, semitendinosus, adductor, sartorius, gracilis, tibialis anterior, tibialis posterior, soleus, medial head of gastrocnemius, and lateral head of gastrocnemius) was measured in four cross-sections: at the trunk, pelvis, thigh, and lower leg. RESULTS: SUVmax was significantly greater in: iliacus and adductor compared to vastus medialis, vastus lateralis, biceps, semitendinosus, gracilis, tibialis anterior, and gastrocnemius; psoas major compared to all muscles except for gluteus minimus and adductor; gluteus minimus compared to all muscles except for iliacus, psoas major, gluteus medius, and adductor; and gluteus medius compared to semitendinosus and gracilis. CONCLUSIONS: After SLR, SUVmax was significantly greater in iliacus, psoas major, gluteus minimus, gluteus medius, and adductor compared to some of the other muscles. Performing SLR increased glucose metabolism of the above muscles in particular, and this may have increased their activity levels.
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Prueba de Esfuerzo , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Músculo Cuádriceps/diagnóstico por imagen , Músculo Cuádriceps/fisiología , Adulto , Terapia por Ejercicio/métodos , Voluntarios Sanos , Humanos , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/fisiología , Masculino , Contracción Muscular/fisiología , Relajación Muscular/fisiología , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/rehabilitación , Valores de Referencia , MuestreoRESUMEN
BACKGROUND: Thyroid function in patients with Grave's disease is usually evaluated by thyroid scintigraphy with radioactive iodine. Recently, dual-energy computed tomography (DECT) with two different energy X-rays can calculate iodine concentrations and can be applied for iodine measurements in thyroid glands. This study aimed to assess the potential use of DECT for the functional assessment of the thyroid gland. METHODS: Thirteen patients with Grave's disease treated at our hospital from May to September 2015 were included in this retrospective study. Before treatments, all subjects had undergone both iodine scintigraphy [three and 24 h after oral administration of 123I (20 µCi)] and non-enhanced DECT. The region of interests (ROIs) were placed in both lobes of the thyroid glands, and CT values (HU: Hounsfield unit) and iodine concentrations (mg/mL) calculated from DECT images were measured. The correlation between CT values and iodine concentrations from DECT in the thyroid gland was evaluated and then the iodine concentrations were compared with radioactive iodine uptake ratios by thyroid scintigraphy. RESULTS: Mean (±SD) 123I uptake increased from 46.3 (±22.2) % (range, 11.1-80.1) at 3 h, to 66.5 (±15.2) % (range, 40.0-86.1) at 24 h (p < 0.01). CT values ranged from 34.5 to 98.7 HU [mean: 67.8 (±18.6)], while the iodine concentrations calculated with DECT ranged from 0.0 to 1.3 mg/mL [mean: 0.5 (±0.4)]. A moderate positive correlation between CT values and the calculated iodine concentrations in the thyroid gland was seen (R = 0.429, p < 0.05). A significant negative correlation between 123I uptake at 3 h and iodine concentration by DECT were seen (R = -0.680, p < 0.05), although no correlation was observed between 123I uptake at 3 h and CT values (p = 0.087). No correlation was observed between 123I uptake at 24 h and CT values (p = 0.153) or that between 123I uptake at 24 h and iodine concentration by DECT (p = 0.073). CONCLUSION: The negative correlation of 123I uptake at 3 h with iodine concentration evaluated by DECT was better than that observed with simple CT value. DECT may have a potential role in the evaluation of iodine turnover in hyperthyroid patients.