RESUMEN

BACKGROUND: The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750. RESULTS: Ex vivo analysis showed 2.1 ± 0.4%, 37.6 ± 6.3% and 38.5 ± 6.2% injected dose/g accumulated in the tumors at 15 min, 24 h and 48 h respectively. Tumor uptake was significantly decreased in pretreated with excess of bevacizumab (p = 0.002). Immunofluorescence analysis showed strong staining of anti-CD 31 antibody around the blood vessels. Anti-VEGF-A and bevacizumab showed heterogeneous expression throughout the tumor. CONCLUSIONS: Current study successfully detected the VEGF expression in HT29 colorectal cancer xenografts, signifying as a potential agent for non-invasive imaging of VEGF expression, which may be applied in clinical practice.

Asunto(s)

Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias del Colon/diagnóstico , Factor A de Crecimiento Endotelial Vascular/aislamiento & purificación , Animales , Anticuerpos Monoclonales Humanizados/química , Bevacizumab , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Diagnóstico por Imagen , Colorantes Fluorescentes/química , Regulación Neoplásica de la Expresión Génica , Células HT29 , Humanos , Ratones , Espectroscopía Infrarroja Corta , Factor A de Crecimiento Endotelial Vascular/genética , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

PURPOSE: We examined the possible efficacy of the yttrium-90 ((90)Y)-labeled anti-CDH3/P-cadherin mouse monoclonal antibody (MAb-6) in radioimmunotherapy (RIT) for lung and colorectal cancers that express CDH3/P-cadherin. EXPERIMENTAL DESIGN: MAb-6 was established using genetic immunization. The biodistribution of MAb-6 in nude mice with lung and colorectal cancers was examined by administering indium-111((111)In)-labeled MAb-6 to mice. The mice were prepared by inoculation of CDH3/P-cadherin-positive (EBC1, H1373, and SW948) and CDH3/P-cadherin-negative (A549 and RKO) tumor cells. Therapeutic effects and toxicity were investigated by administration of (90)Y-labeled MAb-6 ((90)Y-MAb-6) to EBC, H1373, and SW948-inoculated mice. RESULTS: Our in vivo results confirmed the specific binding of MAb-6 to tumor cells after intravenous injections of (111)In-labeled MAb-6 to mice with tumors expressing CDH3/P-cadherin. A single intravenous injection of (90)Y-MAb-6 (100 µCi) significantly suppressed tumor growth in mice with tumors expressing CDH3/P-cadherin. Furthermore, two injections of (90)Y-MAb-6 led to complete tumor regression in H1373-inoculated mice without any detectable toxicity. CONCLUSIONS: Our findings demonstrate that CDH3/P-cadherin-targeting RIT with (90)Y-MAb-6 is a promising strategy for the treatment for cancers expressing CDH3/P-cadherin.

Asunto(s)

Cadherinas/antagonistas & inhibidores , Neoplasias Colorrectales/radioterapia , Neoplasias Pulmonares/radioterapia , Radioinmunoterapia/métodos , Animales , Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Western Blotting , Línea Celular Tumoral , Femenino , Citometría de Flujo , Humanos , Ratones , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Radioisótopos de Itrio/farmacología

RESUMEN

Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for the development of tumor vasculature. The aim of this study was to image VEGF expression with (64)Cu-labeled anti-VEGF antibody (bevacizumab) non-invasively, and to see whether or not the expression was correlated with tumor accumulation in colorectal cancer xenografts. Bevacizumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with (64)Cu. In vivo biodistribution studies and positron emission tomography (PET) imaging were performed on mice bearing human colorectal cancer (HT29) xenografts after injection of (64)Cu-DOTA-bevacizumab, which showed clear accumulation of (64)Cu-DOTA-bevacizumab in the tumor (22.7 ± 1.0 %ID/g, 24 ± 0.2 %ID/g, 19.0 ± 2.5 %ID/g at 24, 48 and 72 h, respectively). Tumor accumulation of (64)Cu-DOTA-bevacizumab was significantly correlated with VEGF expression as measured by western blot (ρ = 0.81, P = 0.004). Vascular endothelial growth factor blocking with unlabeled bevacizumab significantly reduced tumor accumulation of (64) Cu-DOTA- bevacizumab (9.7 ± 1.2 %ID/g, P < 0.001) at 48 h. Interestingly, the blood concentration of VEGF in the mice treated with excess fold of bevacizumab was significantly higher than those without at 48 h (25.5 ± 4.6 %ID/g vs 6.5 ± 2.1 %ID/g, P = 0.0016). Liver uptake decreased from 24 h (17.2 ± 1.7 %ID/g) to 48 h (13.0 ± 4.2 %ID/g) and 72 h (10.6 ± 1.5 %ID/g) due to hepatic clearance of the tracer. The present study successfully showed (64) Cu-DOTA-bevacizumab as a potential PET tracer for non-invasive imaging of VEGF expression in colorectal cancer xenografts.

Asunto(s)

Anticuerpos Monoclonales , Radioisótopos de Cobre , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/análisis , Animales , Anticuerpos Monoclonales Humanizados , Bevacizumab , Western Blotting , Femenino , Células HT29 , Humanos , Inmunohistoquímica , Marcaje Isotópico , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Distribución Tisular , Trasplante Heterólogo

RESUMEN

We report a case of renal failure associated with the ingestion of bee pollen containing nutritional supplement. A 49-year-old male patient who had been ingesting a nutritional supplement for more than five months had breathing difficulties, anuria, exceptional weight gain (20 kg) due to systemic edema, and loss of appetite. A renal biopsy confirmed interstitial nephritis with the presence of eosinophils, which is suggestive of drug-induced acute renal failure. The nutritional supplement was ceased and hemodialysis begun. The patient's condition improved after several hemodialysis sessions, which were then stopped. Current information regarding the adverse effects of bee pollen is not very robust, therefore potential damage should be kept in mind before ingesting nutritional supplements in which it is contained. This report serves as an important reminder to the public as well as healthcare providers of the potential of renal failure related to nutritional supplements.

Asunto(s)

Lesión Renal Aguda/etiología , Abejas , Suplementos Dietéticos/efectos adversos , Polen/efectos adversos , Rinitis Alérgica Estacional/complicaciones , Lesión Renal Aguda/terapia , Animales , Anuria/etiología , Edema/etiología , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal/métodos , Aumento de Peso

RESUMEN

Non-small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of (64)Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with (64)Cu. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/neu overexpression (NCI-H2170) and negative expression (NCI-H520). Imaging of Her2/neu expression was performed in NCI-H2170 tumor-bearing mice with (64)Cu-DOTA-trastuzumab PET and (64)Cu-DOTA-IgG. In vitro studies revealed specific binding of DOTA-trastuzumab in the Her2/neu positive NCI-H2170 cells, while no binding was seen in the Her2/neu negative NCI-H520 cell line. Biodistribution and PET studies revealed a significantly high accumulation of (64)Cu-DOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 and 48 h post-injection (21.4 +/- 1.4% and 23.2 +/- 5.1% injection dose/gram (% ID/g), respectively). PET imaging of Her2/neu negative NCI-H520 tumors showed much less uptake of (64)Cu-DOTA-trastuzumab (4.0% ID/g). The NCI-H2170 tumor uptake of (64)Cu-DOTA-trastuzumab was significantly higher than that of (64)Cu-DOTA-IgG (P < 0.0001). (64)Cu-DOTA-trastuzumab showed a very clear image of a Her2/neu positive tumor and appeared to be effective as a PET tracer for imaging of Her2/neu gene expression in NSCLC, suggesting its potential clinical use for identifying patients that might benefit from trastuzumab-based therapy.

Asunto(s)

Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tomografía de Emisión de Positrones/métodos , Receptor ErbB-2/metabolismo , Animales , Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapéutico , Distribución Tisular/genética , Trastuzumab

RESUMEN

OBJECTIVE: Clinical application of FDG-PET in head and neck cancer includes identification of metastases, unknown primary head and neck malignancy, or second primary carcinoma, and also recurrent tumor after treatment. In this study, the additional value of PET/CT fusion images over PET images alone was evaluated in patients with initial staging and follow up of head and neck malignancy. METHODS: Forty patients with suspected primary head and neck malignancy and 129 patients with suspected relapse after treatment of head and neck malignancy were included. FDG-PET/CT study was performed after the intravenous administration of FDG (5 MBq/kg). Target of evaluation was set at primary tumor, cervical lymph node, and whole body. PET images and PET with CT fusion images were compared. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results of PET and PET/CT were compared with postoperative histopathological examination, and case by case comparison of PET and PET/CT results for each region was performed. The additional value of CT images over PET only images was assessed. Statistical differences in sensitivity and specificity were evaluated. RESULTS: In the comparative evaluation of 507 targets by PET alone and PET/CT, 401 targets showed agreement of the results. Of the 106 discordant targets, 103 showed a positive result on PET alone and negative result on PET/CT. These results showed a significant difference (p< 0.01). Sensitivity of PET/CT was slightly higher than that of PET without statistical significance, while specificity of PET/CT was significantly higher than that of PET alone (Initial staging: 90.5% vs. 62.2%, p < 0.01; Follow up: 97.2% vs. 74.4%, p < 0.01). In Fisher's direct probability test, a significant difference was noted in the sensitivity (Initial staging: 91.3% vs. 87.0%, p < 0.01; Follow up: 93.9% vs. 91.4%, p <0.01). CONCLUSIONS: Combined PET/CT showed improved diagnostic performance than PET alone by decreasing the number of false positive findings in patients with initial staging and follow up of head and neck malignancy.

Asunto(s)

Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Transporte Biológico , Reacciones Falso Positivas , Femenino , Fluorodesoxiglucosa F18/metabolismo , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Masculino , Estadificación de Neoplasias

RESUMEN

The aim of this study was to evaluate the effectiveness of oral iron to manage anemia in long-term hemodialysis (HD) patients using ultrapure dialysate. This study was prospectively conducted on 23 patients (11 males and 12 females; median age 60 years, range 35-81) who underwent HD in our hospital from March to September 2007. The patients were randomly assigned to two treatment groups. The first group of 11 patients received ferrous fumarate 305 mg per oral tablet once a day, while the second group of 12 patients received infusions of 50 mg iron in a 0.9% sodium chloride solution. At the end of the 6-month treatment, patients receiving oral iron and intravenous iron had a significant increase in transferrin saturation from baseline (20.1±8.9 to 29.7±7.2; p=0.011 and 17.4±6.1 to 33.7±8.6; p=0.0001, respectively) and ferritin (32.6±15.4 to 115.4±28.2; p=0.0001 and 57.8±26.7 to 183.5±47.5; p=0.0002, respectively). In both groups, hemoglobin, hematocrit and dry weight were increased, but did not reach statistical significance. Moreover, both groups showed a significant reduction in the mean weekly erythropoietin dose from baseline (5,590.9±1,513.6 to 3,727.3±1,618.1; p=0.011 and 6,775.8±2,292.2 to 4,375.0±2,473.7; p=0.027, respectively). Oral iron is indeed as effective as intravenous iron in managing anemia in HD patients using ultrapure dialysate.

RESUMEN

OBJECTIVE: In-111 ((111)In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ((64)Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a (64)Cu-labeled octreotide analog, (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D: -Phe(1)-Tyr(3)-octreotide ((64)Cu-DOTA-TOC). METHODS: (64)Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 degrees C. The stability of (64)Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of (64)Cu-DOTA-TOC and (111)In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of (64)Cu-DOTA-TOC or (64)Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ((64)Cu-TETA-OC). The tumor was imaged using (64)Cu-DOTA-TOC, (64)Cu-TETA-OC, and FDG with an animal PET scanner. RESULTS: (64)Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. (64)Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of (64)Cu was higher than that of (111)In in all organs except kidney. In tumor-bearing mice, (64)Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 +/- 1.17 at 6 h after administration. (64)Cu-DOTA-TOC showed significantly higher accumulation in the tumor than (64)Cu-TETA-OC. (64)Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of (18)F-FDG PET and very similar to that of (64)Cu-TETA-OC. CONCLUSIONS: (64)Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.

Asunto(s)

Radioisótopos de Cobre/química , Regulación Neoplásica de la Expresión Génica , Neoplasias/metabolismo , Octreótido/análogos & derivados , Tomografía de Emisión de Positrones/métodos , Receptores de Somatostatina/metabolismo , Animales , Línea Celular Tumoral , Humanos , Marcaje Isotópico , Ratones , Neoplasias/diagnóstico por imagen , Neoplasias/genética , Octreótido/química , Octreótido/metabolismo , Octreótido/farmacocinética , Compuestos Organometálicos/metabolismo , Distribución Tisular

RESUMEN

The present study aimed to develop a monoclonal antibody (mAb)-based double functional probe for PET and near-infrared fluorescence (NIRF) targeting CD20 and to cross validate the targeting efficacy of this dual functional probe. NuB2, anti CD20 mAb was conjugated with Alexa Fluor 750 and 64Cu through DOTA chelator. PET and NIRF imaging was carried out at 30 min and 24 h post-injection with 64Cu-DOTA-NuB2-Alexa Fluor 750 in CD20 positive Raji lymphoma-bearing mice. Fluorescence intensity and radio-activity were studied by ex vivo biodistribution study at 30 min, 24 and 48 h after injection. Raji tumor showed significantly higher uptake of DOTA-NuB2-Alexa Fluor 750 than that of DOTA-Alexa Fluor 750 (p<0.05). Significant correlation was obtained between the organ-to-muscle ratios measured by the radioactivity and fluorescence intensity (p<2.2e-16, r=0.94). Our findings demonstrate the effectiveness and feasibility of preparing an effective mAb-based dual functional imaging agent for PET and NIRF targeting the CD20 expression in lymphoma.

Asunto(s)

Anticuerpos Monoclonales , Antígenos CD20/inmunología , Linfoma/diagnóstico , Técnicas de Sonda Molecular , Tomografía de Emisión de Positrones , Espectroscopía Infrarroja Corta , Animales , Línea Celular Tumoral , Quelantes , Radioisótopos de Cobre , Estudios de Factibilidad , Femenino , Colorantes Fluorescentes , Compuestos Heterocíclicos con 1 Anillo , Humanos , Linfoma/diagnóstico por imagen , Linfoma/inmunología , Linfoma/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Reproducibilidad de los Resultados , Succinimidas , Factores de Tiempo

RESUMEN

OBJECTIVE: Frizzled homolog 10 (FZD10) is expressed at high levels on the cell surface of almost all synovial sarcoma tissues, but is absent in most normal organs. In a previous study, yttrium-90 ((90)Y)-labeled anti-FZD10 antibody (MAb 92-13) showed considerable therapeutic efficacy in synovial sarcoma cell-bearing mice. The purpose of the present study was to elucidate the factors associated with this therapeutic efficacy of (90)Y-MAb 92-13. METHODS: FZD10 expression levels of SYO-1 (FZD10-overexpressing synovial sarcoma cell line) and DLD-1/FZD10 (FZD10-transfected DLD-1 cell) were determined by the cell binding assay, and their radiosensitivity was evaluated by incubation with (90)Y-MAb 92-13 in vitro. Biodistribution study of indium-111 ((111)In)-MAb 92-13 was performed in SYO-1 and DLD-1/FZD10 tumor-bearing mice. For therapeutic studies, SYO-1 and DLD-1/FZD10 tumor-bearing mice were treated with (90)Y-MAb 92-13 (100, 150, and 200 muCi), after which the change in tumor volume was measured. Immunohistochemical staining was performed on the excised tumor. RESULTS: Expression level of FZD10 on DLD-1/FZD10 was much greater than that on SYO-1. The accumulation of (111)In-MAb 92-13 was much higher in DLD-1/FZD10 tumor-bearing mice than in SYO-1 tumor-bearing mice (49.0 +/- 4.2 and 22.0 +/- 4.5% ID/g, respectively, at 48 h after administration). In SYO-1 tumor, substantial tumor size reduction was observed in all mice treated with (90)Y-MAb 92-13 (tumor volume decreased to less than 0.1 cm(3) at 11 days after treatment) and tumor regrowth was not observed in most of them. In contrast, only slow progression was observed in DLD-1/FZD10 tumor. When incubated with (90)Y-MAb 92-13, high radioactivity was needed to damage DLD-1/FZD10. Immunohistochemical study indicated apoptosis of SYO-1 tumor. CONCLUSIONS: The therapeutic efficacy of RIT seems to largely depend on the tumor radiosensitivity.

Asunto(s)

Receptores Frizzled/metabolismo , Neoplasias/patología , Neoplasias/radioterapia , Tolerancia a Radiación , Radioinmunoterapia , Receptores Acoplados a Proteínas G/metabolismo , Animales , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Transporte Biológico , Línea Celular Tumoral , Supervivencia Celular , Humanos , Inmunohistoquímica , Ratones , Neoplasias/metabolismo , Neoplasias/terapia , Distribución Tisular , Resultado del Tratamiento

RESUMEN

Hepatocellular carcinoma (HCC) has variable 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and the relationship between 18F-FDG uptake with the expression of glucose transporters (Gluts) and hexokinase II (HK-II) has not been extensively examined. Present study explored the role of 18F-FDG positron emission tomography (PET) as a clinical significance and the association with Gluts and HK-II in patients with HCC. Whole body 18F-FDG PET, immunohistochemistry and western blot analysis of Glut-1 to Glut-5 and HK-II were performed in 31 patients (24 male and 7 female, range 48-75 years) with HCC. Significant correlation was found between 18F-FDG uptake and overall expression of Glut-2 (rho=0.55, p=0.002) and HK-II (rho=0.37, p=0.04). Expression of HK-II was correlated with Glut-2 (rho=0.57, p=0.0009) but not with other Gluts, which indicated that Glut-2 is a major glucose transporter. The prognosis of patients with SUV >/=2 and positive Glut-2 were significantly worse than that with SUV <2 and negative Glut-2 (p=0.005 and p=0.03), respectively. Multivariate analysis showed that SUV and lymph node metastasis were independent prognostic factors. The present study indicated that combined evaluation of 18F-FDG uptake and expression of Glut-2 might have an important role for management of patients with HCC.

Asunto(s)

Carcinoma Hepatocelular/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Glucosa/metabolismo , Hexoquinasa/metabolismo , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Anciano , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Femenino , Fluorodesoxiglucosa F18/metabolismo , Transportador de Glucosa de Tipo 2/metabolismo , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Radiofármacos/metabolismo , Medición de Riesgo , Resultado del Tratamiento

RESUMEN

Cholangiocellular carcinoma (CCC) has been reported to have a high glucose uptake; however, the mechanism of glucose entry into these cells is still unclear. We investigated the relationship between [(18)F]-2-fluro-2-deoxy-D-glucose ((18)F-FDG) uptake and the expression of facilitative glucose transporters (Glut) and hexokinase (HK) II, as well as the association between the expression of different histological types of CCC. The expression of Glut (1-5) and HK II was studied using immunohistochemistry of 26 patients with CCC who underwent whole-body (18)F-FDG positron emission tomography before surgery or biopsy. CCC expressed immunohistochemically detectable Glut 1 in 81%, Glut 2 in 54%, Glut 3 in 19%, and HK II in 77% of the total cases. Glut 1, Glut 2, Glut 3, and HK II were more often detected in moderately differentiated and poorly differentiated than in well-differentiated CCC. A significant correlation was observed between (18)F-FDG uptake and the staining scores of Glut 1 and HK II (P = 0.02, rho = 0.45 and P = 0.001, rho = 0.59). The staining scores of Glut 1 and HK II were also significantly correlated (P = 0.002, rho = 0.3). Multivariate regression analysis revealed that lymph-node metastasis was independently associated with (18)F-FDG uptake. Our study showed a significant association between the expression of Glut 1 and HK II with (18)F-FDG uptake, indicating that Glut 1 is a major glucose transporter expressed in CCC and that HK II contributes to the increased metabolism of glucose, especially in moderately and poorly differentiated CCC.

Asunto(s)

Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos , Colangiocarcinoma/metabolismo , Fluorodesoxiglucosa F18/farmacocinética , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Hexoquinasa/metabolismo , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/enzimología , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/enzimología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad

RESUMEN

We report the results of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) and immunohistochemical staining of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in patients with hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) to observe the variation in (18)F-FDG uptake and variation in expression of Glut-1 and HK-II in these hepatic tumors. In the case of HCC, moderate (18)F-FDG uptake and strong expression of HK-II were detected, whereas Glut-1 was not expressed. Conversely, CCC showed high (18)F-FDG uptake and increased expression of Glut-1 but HK-II was not expressed. The variation in the (18)F-FDG uptake and expression of Glut 1 and HK-II in HCC and CCC might be owing to the difference in origin and the different mechanisms involved in glucose uptake, rate of glucose transporters, and hexokinase activity involved in the glycolytic pathway.

Asunto(s)

Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Transportador de Glucosa de Tipo 1/sangre , Hexoquinasa/sangre , Neoplasias Hepáticas/diagnóstico por imagen , Anciano , Carcinoma Hepatocelular/sangre , Colangiocarcinoma/sangre , Colangiocarcinoma/metabolismo , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/metabolismo , Persona de Mediana Edad , Cintigrafía , Radiofármacos/farmacocinética

RESUMEN

The aim of this study was to evaluate the role of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in the restaging of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA). This study was performed on 33 lesions in 24 patients with HCC. 18F-FDG PET and computed tomography (CT) studies were performed in all patients before treatment. PET acquisition was started 50-60 min after injection of 18F-FDG (5-6 MBq/kg). Semi-quantitative analysis using Standardized Uptake Value (SUV) was measured for the evaluation of tumour 18F-FDG uptake. All patients underwent RFA treatment and were followed up at least 2 years with 18F-FDG PET, CT and clinical evaluation in the interval of every 3 months in the first year and every 6 months in the second year. 18F-FDG PET detected recurrence earlier than CT between 4-6 months in 2 patients and between 7-9 months in 6 patients whereas CT was positive in 4 patients. Overall detection rate of recurrence with 18F-FDG PET was 92% which was higher than that of CT (75%). Statistically significant difference in the SUV was observed between well and moderately differentiated HCC (p=0.033) and also between well and poorly differentiated HCC (p=0.037). The size of tumours showed a significant correlation with the time of recurrence (p<0.00033, r=0.8601, n=12). The results of this study indicate that 18F-FDG PET could detect recurrence earlier in patients with HCC treated with RFA, as compared with CT and could diagnose extrahepatic lesions. SUV showed a significant correlation with time of recurrence after RFA. 18F-FDG PET may be a dominant imaging modality as a follow-up procedure of HCC after RFA, in terms of early detection of recurrence.

Asunto(s)

Carcinoma Hepatocelular/diagnóstico por imagen , Ablación por Catéter , Fluorodesoxiglucosa F18 , Neoplasias Hepáticas/diagnóstico por imagen , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Recurrencia