Nuestros investigadores

José Ángel Richter Echevarria

Publicaciones científicas más recientes (desde 2010)

Autores: Prieto, Elena; Garcia-Velloso, Maria Jose; Rodríguez-Fraile, M; et al.
Revista: PHYSICA MEDICA
ISSN 1120-1797  Vol. 46  2018  págs. 134-139
A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence
Autores: Marti-Climent, JM; Prieto, Elena; Morán, Verónica; et al.
Revista: EJNMMI RESEARCH
ISSN 2191-219X  Vol. 7  Nº 1  2017  págs. 37
The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.
Autores: Morales, María Isabel; García, Berta; et al.
Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN 2253-654X  Vol. 36  Nº Supl 1  2017  págs. 10
n pacientes con mieloma múltiple el FDG-PET/CT es una herramienta sensible en la valoración de respuesta, permite la detección de enfermedad extramedular y complementa la valoración de la enfermedad mínima residual. La persistencia de captación de FDG en pacientes en RC puede predecir la recaída
Autores: Garcia-Velloso, Maria Jose; Bastarrika, Gorka; de Torres, Juan Pablo; et al.
Revista: LUNG CANCER
ISSN 0169-5002  Vol. 97  2016  págs. 81-86
A major drawback of lung cancer screening programs is the high frequency of false-positive findings on computed tomography (CT). We investigated the accuracy of selective 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan in assessing radiologically indeterminate lung nodules detected in lung cancer screening. Methods: FDG PET/CT was performed to characterize 64 baseline lung nodules >10 mm and 36 incidence nodules detected on low-dose CT screening in asymptomatic current or former smokers (83 men, age range 40¿83 years) at high risk for lung cancer. CT images were acquired without intravenous contrast. Nodules were analyzed by size, density, and metabolic activity and visual scored on a 5-point scale for FDG uptake. Nodules were classified as negative for malignancy when no FDG uptake was observed, or positive when focal uptake was observed in the visual analysis, and the maximum standardized uptake value (SUVmax) was measured. Final diagnosis was based on histopathological evaluation or at least 24 months of follow-up. Results: A total of 100 nodules were included. The prevalence of lung cancer was 1%. The sensitivity, specificity, NPV and PPV of visual analysis to detect malignancy were 84%, 95%, 91%, and 91%, respectively, with an accuracy of 91% (AUC 0.893). FDG PET/CT accurately detected 31 malignant tumors (diameters 9¿42 mm, SUVmax range 0.6¿14.2) and was falsely negative in 6 patients. With SUVmax threshold
Autores: Pascual, Juan Ignacio; et al.
Revista: PROSTATE
ISSN 0270-4137  Vol. 76  Nº 1  2016  págs. 3 - 12
BACKGROUND: Index lesion characterization is important in the evaluation of primary prostate carcinoma (PPC). The aim of this study was to analyze the contribution of (11) C-Choline PET/CT and the Apparent Diffusion Coefficient maps (ADC) in detecting the Index Lesion and clinically significant tumors in PPC. METHODS: Twenty-one untreated patients with biopsy-proven PPC and candidates for radical prostatectomy (RP) were prospectively evaluated by means of Ultra-High Definition PET/CT and 3T MRI, which included T2-weighted imaging (T2WI) and ADC maps obtained from diffusion weighted imaging (DWI). Independent experts analyzed all the images separately and were unaware of the pathological data. In each case, the Index lesion was defined as the largest tumor measured on histopathology (Index H). In addition, the largest lesion observed on MRI (Index MRI) and the highest avid (11) C-Choline uptake lesion (Index PET) were obtained. The Gleason scores (GS) of the tumors were determined. PET/CT and ADC map quantitative parameters were also calculated. Measures of correlation among imaging parameters as well as the sensitivity (S), specificity (Sp), negative and positive predictive values (NPV and PPV) for tumor detection were analyzed. All data was validated with the pathological study. RESULTS: In the morphological study, 139 foci of carcinoma were identified, 47 of which corresponded to clinically significant tumors (>0.5¿cm(3) ). The remaining foci presented a maximum diameter (dmax ) of 0.1¿cm¿±¿SD 0.75 and were not classified as clinically significant. Thirty-two tumors presented a GS (3¿+¿3), nine GS (3¿+¿4), and six GS (4¿+¿3). A total of 21 Index H (dmax ¿=¿1.37¿cm SD¿±¿0.61) were identified. The S, Sp, NPV, and PPV for tumor detection with PET were 100%, 70%, 83%, 100%, and for MRI were 46%, 100%, 100%, 54%, respectively. Both Index PET and Index MRI were complementary and identified 95% of the Index H when quantitative criteria were used. CONCLUSION: In spite of the fact that PET imaging has higher tumor sensitivity than MRI, (11) C-Choline PET and ADC maps have complementary roles in the evaluation of Index Lesion in PPC. Index PET and Index MRI could be complementary targets in the therapeutic planning of PPC.
Autores: Morán, Verónica; Prieto, Elena; García, Berta; et al.
Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN 2253-654X  Vol. 35  Nº 3  2016  págs. 175-85
It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions
Autores: Morán, Verónica; Prieto, Elena; García, Berta; et al.
Revista: REVISTA ESPANOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN 2253-654X  Vol. 35  Nº 3  2016  págs. 175 - 185
Objectives: The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. Material and methods: A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0 m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). Results: During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 mu Sv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. Conclusion: It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.
Autores: Conchillo, María de los Ángeles; et al.
Revista: EUROPEAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
ISSN 0954-691X  Vol. 28  Nº 2  2016  págs. 139 - 145
Objective Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. Patients and methods We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. Results REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, â-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P< 0.05), nonprotein respiratory quotient (P< 0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P< 0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. Conclusion Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.
Autores: García, Berta; Morales, María Isabel; Guillen Valderrama, E; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 43  Nº Supl.1.  2016  págs. S127 - S127
Autores: Figueroa, Rocío; Marcos-Jubilar, María; García, Berta; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 101  Nº Supl. 1  2016  págs. 524
Autores: Prieto, Elena; Morán, Verónica; García, Berta; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 43  Nº Supl.1  2016  págs. S528 - S528
Autores: Prieto, Elena; Marti-Climent, JM; Morán, Verónica; et al.
Revista: PHYSICA MEDICA
ISSN 1120-1797  Vol. 31  Nº 8  2015  págs. 948-955
Optimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.
Autores: Marti-Climent, JM; Collantes M; Jauregui-Osoro M; et al.
Revista: EJNMMI RESEARCH
ISSN 2191-219X  Vol. 15  Nº 1  2015  págs. 70
(18)F]-tetrafluoroborate is a very useful radiotracer for PET thyroid imaging in primates, with a characteristic biodistribution in organs expressing NIS. It delivers an effective dose slightly higher than the dose produced by (99m)Tc-pertechnetate but much lower than that produced by radioiodine in the form of (131)INa, (123)INa, or (124)INa.
Autores: Sancho, Lidia; Guillen Valderrama, E; Garcia-Velloso, Maria Jose; et al.
Revista: JOURNAL OF NUCLEAR MEDICINE
ISSN 0161-5505  Vol. 56  Nº Supl.3  2015  págs. 1273
Autores: Pérez-Pevida, Belén; Sancho, Lidia; Guillen Valderrama, E; et al.
Revista: DIABETOLOGIA
ISSN 0012-186X  Vol. 58  Nº Supl. 1  2015  págs. 342
Autores: Sancho, Lidia; Guillen Valderrama, E; Pérez-Pevida, Belén; et al.
Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN 2253-8070  Vol. 34  Nº Supl.1  2015  págs. 79
Conclusiones: La interrupción de M 48h fue mejor que 24h para la reducción de la CI de 18F-FDG en pacientes con DM2 y mejoró significativamente la calidad de los estudios 18F-FDG-PET/CT. Aunque la glucemia aumentó tras la interrupción de M, permaneció en rangos aceptables.
Autores: Caicedo C; Garcia-Velloso, Maria Jose; Lozano, María D; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 41  Nº 11  2014  págs. 2058-65
PURPOSE: The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [(18)F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC. METHODS: Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [(18)F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [(18)F]FDG PET/CT for predicting KRAS mutation. RESULTS: From 102 patients staged using [(18)F]FDG PET/CT, 28 (27%) had KRAS mutation (KRAS+), 22 (22%) had EGFR mutation (EGFR+) and 52 (51%) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [(18)F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p¿<¿0.001). No significant differences were observed in [(18)F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p¿<¿0.001).
Autores: Marti-Climent, JM; Prieto, Elena; Elosúa C; et al.
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 41  Nº 9  2014  págs. 092503
Qualitative and quantitative 90Y PET imaging improved with the introduction of TOF in a PET/CT scanner, thereby allowing the visualization of microsphere deposition in lesions not visible in non-TOF images. This technique accurately quantifies the total activity delivered to the liver during radioembolization with (90)Y-microspheres and allows dose estimation.
Autores: Prieto, Elena; Marti-Climent, JM; Marisol Gómez Fernández; et al.
Revista: INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
ISSN 2222-3959  Vol. 33  Nº 2  2014  págs. 79 - 86
Objetivo Diseñar una técnica novedosa de adquisición ex-vivo para establecer un marco común de validación de diferentes técnicas de segmentación para imágenes PET oncológicas. Evaluar sobre estas imágenes el funcionamiento de varios algoritmos de segmentación automática. Material y métodos En 15 pacientes oncológicos se realizaron estudios PET ex-vivo de las piezas quirúrgicas extraídas durante la cirugía, previa inyección de 18F-FDG, adquiriéndose imágenes en 2 tomógrafos: un PET/CT clínico y un tomógrafo PET de alta resolución. Se determinó el volumen tumoral real en cada paciente, generándose una imagen de referencia para la segmentación de cada tumor. Las imágenes se segmentaron con 12 algoritmos automáticos y con un método estándar para PET (umbral relativo del 42%) y se evaluaron los resultados mediante parámetros cuantitativos. Resultados La segmentación de imágenes PET de piezas quirúrgicas ha demostrado que para imágenes PET de alta resolución 8 de las 12 técnicas de segmentación evaluadas superan al método estándar del 42%. Sin embargo, ninguno de los algoritmos superó al método estándar en las imágenes procedentes del PET/CT clínico. Debido al gran interés de este conjunto de imágenes PET, todos los estudios se han publicado a través de Internet con el fin de servir de marco común de validación y comparación de diferentes técnicas de segmentación. Conclusiones Se ha propuesto una técnica novedosa para validar técnicas de segmentación para imágenes PET oncológicas, adquiriéndose estudios ex-vivo de piezas quirúrgicas. Se ha demostrado la utilidad de este conjunto de imágenes PET mediante la evaluación de varios algoritmos automáticos.
Autores: Marti-Climent, JM; Garcia-Velloso, Maria Jose; et al.
Revista: INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
ISSN 2222-3959  Vol. 33  Nº 5  2014  págs. 280-285
Objectives: To investigate quantitative methods of tumor proliferation using 3'-[F-18]fluoro-3'-deoxythymidine ([F-18]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [F-18]FLT-PET uptake with the Ki67 index. Material and methods: Thirty patients with newly diagnosed, untreated BC underwent a [F-18]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [F-18]FLT (385 +/- 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. Results: [F-18]FLT uptake parameters decreased significantly (p < 0.001) after treatment: SUV50 = 3.09 +/- 1.21 vs 2.22 +/- 0.96; SUV40 = 3.00 +/- 1.18 vs 2.14 +/- 0.95, Ki_LV(10-3) = 52[22-116] vs 38[13-80] and Ki_DA(10-3) = 49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson = 0.35
Autores: Arbizu, Javier Ignacio; Prieto, Elena; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 10  Nº 9  2013  págs. 1394 - 1405
To introduce, evaluate and validate a voxel-based analysis method of F-18-FDG PET imaging for determining the probability of Alzheimer's disease (AD) in a particular individual. The subject groups for model derivation comprised 80 healthy subjects (HS), 36 patients with mild cognitive impairment (MCI) who converted to AD dementia within 18 months, 85 non-converter MCI patients who did not convert within 24 months, and 67 AD dementia patients with baseline FDG PET scan were recruited from the AD Neuroimaging Initiative (ADNI) database. Additionally, baseline FDG PET scans from 20 HS, 27 MCI and 21 AD dementia patients from our institutional cohort were included for model validation. The analysis technique was designed on the basis of the AD-related hypometabolic convergence index adapted for our laboratory-specific context (AD-PET index), and combined in a multivariable model with age and gender for AD dementia detection (AD score). A logistic regression analysis of different cortical PET indexes and clinical variables was applied to search for relevant predictive factors to include in the multivariable model for the prediction of MCI conversion to AD dementia (AD-Conv score). The resultant scores were stratified into sixtiles for probabilistic diagnosis. The area under the receiver operating characteristic curve (AUC) for the AD score detecting AD dementia in the ADNI database was 0.879, and the observed probability of AD dementia in the six defined groups ranged from 8 % to 100 % in a monotonic trend. For predicting MCI conversion to AD dementia, only the posterior cingulate index, Mini-Mental State Examination (MMSE) score and apolipoprotein E4 genotype (ApoE4) exhibited significant independent effects in the univariable and multivariable models. When only the latter two clinical variables were included in the model, the AUC was 0.742 (95 % CI 0.646 - 0.838), but this increased to 0.804 (95 % CI 0.714 - 0.894, bootstrap p = 0.027) with the addition of the posterior cingulate index (AD-Conv score). Baseline clinical diagnosis of MCI showed 29.7 % of converters after 18 months. The observed probability of conversion in relation to baseline AD-Conv score was 75 % in the high probability group (sixtile 6), 34 % in the medium probability group (merged sixtiles 4 and 5), 20 % in the low probability group (sixtile 3) and 7.5 % in the very low probability group (merged sixtiles 1 and 2). In the validation population, the AD score reached an AUC of 0.948 (95 % CI 0.625 - 0.969) and the AD-Conv score reached 0.968 (95 % CI 0.908 - 1.000), with AD patients and MCI converters included in the highest probability categories. Posterior cingulate hypometabolism, when combined in a multivariable model with age and gender as well as MMSE score and ApoE4 data, improved the determination of the likelihood of patients with MCI converting to AD dementia compared with clinical variables alone. The probabilistic model described here provides a new tool that may aid in the clinical diagnosis of AD and MCI conversion.
Autores: Prieto, Elena; Garcia-Velloso, Maria Jose; et al.
Revista: CLINICAL NUCLEAR MEDICINE
ISSN 0363-9762  Vol. 38  Nº 2  2013  págs. 103-109
Background: Accuracy in the quantification of the SUV is a critical point in PET because proper quantification of tumor uptake is essential for therapy monitoring and prognosis evaluation. Recent advances such as time-of-flight (TOF) and point-spread-function (PSF) reconstructions have dramatically improved detectability. However, first experiences with these techniques have shown a consistent tendency to measure markedly high SUV values, bewildering nuclear medicine physicians and referring clinicians. Purpose: We investigated different reconstruction and quantification procedures to determine the optimum protocol for an accurate SUV quantification in last generation PET scanners. Methods: Both phantom and patient images were evaluated. A complete set of experiments was performed using a body phantom containing 6 spheres with different background levels and contrasts. Whole-body FDG PET/CT of 20 patients with breast and lung cancer was evaluated. One hundred five foci were identified by 2 experienced nuclear medicine physicians. Each acquisition was reconstructed both with classical and advanced (TOF, PSF) reconstruction techniques. Each sphere and each in vivo lesion was quantified with different parameters as follows: SUVmax, SUVmean, and SUV50 (mean within a 50% isocontour). Results: This study has confirmed that quantification with SUVmax produces important overestimation of metabolism in new generation PET scanners. This is a relevant result because, currently, SUVmax is the standard parameter for quantification. SUV50 has been shown as the best alternative, especially when applied to images reconstructed with PSF + TOF. Conclusions: SUV50 provides accurate quantification and should replace SUVmax in PET tomographs incorporating advanced reconstruction techniques. PSF + TOF reconstruction is the optimum for both detection and accurate quantification.
Autores: Marti-Climent, JM; Prieto, Elena; et al.
Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR
ISSN 0212-6982  Vol. 32  Nº 1  2013  págs. 13 - 21
Objective: To characterize the performance of the Biograph mCT PET/CT TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. Material and methods: The PET/CT scanner combines a 64-slice CT and PET scanner that incorporates in the reconstruction the TOF and PSF information. PET operating characteristics were evaluated according to the standard NEMA NU 2-2007, expanding some tests. In addition, different reconstruction algorithms were included, and the intrinsic radiation and tomographic uniformity were also evaluated. Results: The spatial resolution (FWHM) at 1 and 10 cm was 4.4 and 5.3 mm, improving to 2.6 and 2.5 mm when PSF is introduced. Sensitivity was 10.9 and 10.2 Kcps/MBq at 0 and 10 cm from the axis. Scatter fraction was less than 34% at low concentrations and the noise equivalent count rate (NECR) was maximal at 27.8 kBq/mL with 182 Kcps, the intrinsic radiation produced a rate of 4.42 true coincidences per second. Coefficient of variation of the volume and system uniformity were 4.7 and 0.8% respectively. The image quality test showed better results when PSF and TOF were included together. PSF improved the hot spheres contrast and background variability, while TOF improved the cold spheres contrast. Conclusions: The Biograph mCT TrueV scanner has good performance characteristics. The image quality improves when the information from the PSF and the TOF is incorporated in the reconstruction.
Autores: Alfonso, Ana; Redondo M; Rubio T; et al.
Revista: INTERNATIONAL JOURNAL OF CANCER
ISSN 0020-7136  Vol. 133  Nº 9  2013  págs. 2157-2164
Extensive screening strategies to detect occult cancer in patients with unprovoked venous thromboembolism (VTE) are complex and no benefit in terms of survival has been reported. FDG-PET/CT (2-[F-18] fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography), a noninvasive technique for the diagnosis and staging of malignancies, could be useful in this setting. Consecutive patients with a first unprovoked VTE episode were prospectively included. Screening with FDG-PET/CT was performed 3-4 weeks after the index event. If positive, appropriate diagnostic work-up was programmed. Clinical follow-up continued for 2 years. FDG-PET/CT was negative in 68/99 patients (68.7%), while suspicious FDG uptake was detected in 31/99 patients (31.3%). Additional diagnostic work-up confirmed a malignancy in 7/31 patients (22.6%), with six of them at early stage. During follow-up, two patients with negative FDG-PET/CT were diagnosed with cancer. Sensitivity (S), positive (PPV) and negative predictive values (NPV) of FDG-PET/CT as single tool for the detection of occult malignancy were 77.8% (95% CI: 0.51-1), 22.6% (95% CI: 0.08-0.37) and 97.1% (95% CI: 0.93-1), respectively. Median tissue factor (TF) activity in patients with occult cancer was 5.38 pM vs. 2.40 pM in those without cancer (p = 0.03). FDG-PET/CT is feasible for the screening of occult cancer in patients with unprovoked VTE, showing high S and NPV.
Autores: Alfonso, Ana; Redondo M; Rubio T; et al.
Revista: INTERNATIONAL JOURNAL OF CANCER
ISSN 0020-7136  Vol. 133  Nº 9  2013  págs. 2157-2164
Extensive screening strategies to detect occult cancer in patients with unprovoked venous thromboembolism (VTE) are complex and no benefit in terms of survival has been reported. FDG-PET/CT (2-[F-18] fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography), a noninvasive technique for the diagnosis and staging of malignancies, could be useful in this setting. Consecutive patients ¿ 50 years with a first unprovoked VTE episode were prospectively included. Screening with FDG-PET/CT was performed 3¿4 weeks after the index event. If positive, appropriate diagnostic work-up was programmed. Clinical follow-up continued for 2 years. Blood samples were collected to assess coagulation biomarkers. FDG-PET/CT was negative in 68/99 patients (68.7%), while suspicious FDG uptake was detected in 31/99 patients (31.3%). Additional diagnostic work-up confirmed a malignancy in 7/31 patients (22.6%), with six of them at early stage. During follow-up, two patients with negative FDG-PET/CT were diagnosed with cancer. Sensitivity (S), positive (PPV) and negative predictive values (NPV) of FDG-PET/CT as single tool for the detection of occult malignancy were 77.8% (95% CI: 0.51¿1), 22.6% (95% CI: 0.08¿0.37) and 97.1% (95% CI: 0.93¿1), respectively. Median tissue factor (TF) activity in patients with occult cancer was 5.38 pM vs. 2.40 pM in those without cancer (p = 0.03). Limitation of FDG-PET/CT screening to patients with TF activity > 2.8 pM would improve the PPV t
Autores: Baixauli, J; Bellver, Manuel Jose; et al.
Revista: CIRUGIA ESPAÑOLA
ISSN 0009-739X  Vol. 91  Nº Especial Congreso 2  2013  págs. 33
Objetivos: Evaluar la respuesta tumoral a nivel radiológico, metabólico y patológico del tratamiento del cáncer de colon localmente avanzado (CCLA) tratado preoperatoriamente con oxaliplatino y capecitabina. Métodos: Se incluyeron 44 paciente con diagnóstico de CCLA que recibieron tratamiento neoadyuvante y cirugía de colon. Se realizó un análisis retrospectivo. Todos os pacientes fueron estadificados en el momento del diagnóstico y tras recibir la quimioterapia preoperatoria. El diagnóstico clínico se basó en examen físico, endoscopia con toma de biopsia y TAC. En casos seleccionados se empleó PET/TAC. Se evaluó la precisión y la correlación entre los hallazgos descritos por TAC y los referidos en el análisis patológico final a nivel de estadio T, N y TN. Resultados: Tras la quimioterapia se observó una reducción significativa del volumen tumoral medido por TAC del 62.5% (p < 0,001; test Wilcoxon) y del SUV max medido por PET del 38,9% (p = 0,004). No hubo ningún caso de progresión tumoral durante el tratamiento neoadyuvante. La precisión para el estadio T y N fue del 62% y 87%, respectivamente. La precisión para el estadio TN fue del 77%, con un 13.6% y un 9.1% de los pacientes con infra y sobreestadificación, respectivamente. Conclusiones: La quimioterapia preoperatoria basada en oxaliplatino y capecitabina induce una respuesta tumoral mayor a nivel radiológico, metabólico y patológico. La alta precisión y la escasa sobreestadificación hallada en el TAC son de valor a la hora de seleccionar al grupo de pacientes con CCLA que más se podrían beneficiar de un tratamiento neoadyuvante.
Autores: Peñuelas, Iván; Garcia-Velloso, Maria Jose; et al.
Revista: JOURNAL OF ONCOLOGY
ISSN 1687-8450  Vol. 12  Nº 7  2012  págs. 710561
Molecular imaging of breast cancer has undoubtedly permitted a substantial development of the overall diagnostic accuracy of this malignancy in the last years. Accurate tumour staging, design of individually suited therapies, response evaluation, early detection of recurrence and distant lesions have also evolved in parallel with the development of novel molecular imaging approaches. In this context, positron emission tomography (PET) can be probably seen as the most interesting molecular imaging technology with straightforward clinical application for such purposes. Dozens of radiotracers for PET imaging of breast cancer have been tested in laboratory animals. However, in this review we shall focus mainly in the smaller group of PET radiopharmaceuticals that have lead through into the clinical setting. PET imaging can be used to target general metabolic phenomena related to tumoural transformation, including glucose metabolism and cell proliferation, but can also be directed to specific hormone receptors that are characteristic of the breast cancer cell. Many other receptors and transport molecules present in the tumour cells could also be of interest for imaging. Furthermore, molecules related with the tumour microenvironment, tumour induced angiogenesis or even hypoxia could also be used as molecular biomarkers for breast cancer imaging.
Autores: Arbizu, Javier Ignacio; Tejada, Sonia; Marti-Climent, JM; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 39  Nº 5  2012  págs. 771 - 781
PURPOSE: The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. METHODS: We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. RESULTS: Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p¿<¿0.001, ¿¿=¿0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5). CONCLUSION: The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.
Autores: Vegliante, M. C.; Royo, C.; Palomero, J.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 6  Nº 6  2011  págs. e21382
Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications.
Autores: Alfaro, Carlos; Pérez, José Luis; et al.
Revista: The Journal of Immunology
ISSN 0022-1767  Vol. 187  Nº 11  2011  págs. 6130 - 6142
Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-alpha, TNF-alpha, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN-gamma-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing.
Autores: Barba, Javier Fermín; et al.
Revista: ACTAS UROLOGICAS ESPANOLAS
ISSN 0210-4806  Vol. 35  Nº 4  2011  págs. 218 - 224
Autores: Arbizu, Javier Ignacio; Domínguez, Pablo Daniel; Diez Valle, Ricardo; et al.
Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR
ISSN 0212-6982  Vol. 30  Nº 1  2011  págs. 47-65
Autores: Prieto, Elena; Marti-Climent, JM; Arbizu, Javier Ignacio; et al.
Revista: Computers in Biology and Medicine
ISSN 0010-4825  Vol. 40  Nº 1  2010  págs. 75 - 80
Autores: Richter, José Ángel; Robles, Eloy Francisco; Beltrán E; et al.
Revista: BLOOD
ISSN 0006-4971  Vol. 116  Nº 14  2010  págs. 2531 - 2542
In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can be circumvented remain undetermined. We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas. Here we show that BIM epigenetic silencing by concurrent promoter hypermethylation and deacetylation occurs frequently in primary BL samples and BL-derived cell lines. Remarkably, patients with BL with hypermethylated BIM presented lower complete remission rate (24% vs 79%; P = .002) and shorter overall survival (P = .007) than those with BIM-expressing lymphomas, indicating that BIM transcriptional repression may mediate tumor chemoresistance. Accordingly, by combining in vitro and in vivo studies of human BL-xenografts grown in immuno-deficient RAG2(-/-)gamma c(-/-) mice and of murine B220(+)IgM(+) B-cell lymphomas generated in E(mu)-MYC and E(mu)-MYC-BIM(+/-) transgenes, we demonstrate that lymphoma chemoresistance is dictated by BIM gene dosage and is reversible on BIM reactivation by genetic manipulation or after treatment with histone-deacetylase inhibitors. We suggest that the combination of histone-deacetylase inhibitors and high-dose chemotherapy may overcome chemoresistance, achieve durable remission, and improve survival of patients with BL.
Autores: Richter, José Ángel; Rodríguez-Fraile, M; et al.
Revista: Molecular Imaging and Biology
ISSN 1536-1632  Vol. 12  Nº 2  2010  págs. 210 - 217
Autores: Garcia-Velloso, Maria Jose; et al.
Revista: JOURNAL OF NUCLEAR MEDICINE
ISSN 0161-5505  Vol. 51  Nº Supl. 2  2010  págs. 1197
Objectives Sentinel node biopsy (SNB) has become a standard treatment in staging axillary lymph nodes in early breast cancer. However, SNB is an invasive procedure. Breast cancer is frequently characterised by increased 18FDG uptake and many studies have shown encouraging results in detecting axillary lymph node metastases. The aim of this study was to compare SNB and positron emission tomography/computed tomography (PET/CT) imaging, to assess their values in detecting occult axillary metastases. Methods Forty-nine women (mean age 55-year old) with 50 breast cancer (mean primary tumor size 1.97 cm) and clinically negative axilla were enrolled in the study. 18FDG PET was carried out before surgery, using a PET/CT scanner. In all patients, SNB was carried out after identification through lymphoscintigraphy. Patients underwent axillary lymph nodes dissection (ALND) in cases of positive SNB. The results of PET scan were compared with histopathology of SNB and ALND. Results In all, 23 out of the 49 patients (47%) had metastases in axillary nodes. The standardized uptake value (SUV) was related to the histological grading (2.6±1.1 in well differentiated vs 3.7±3.1 in poorly differentiated). Sensitivity of FDG-PET scan for detection of axillary lymph node metastases in this series was very low (13%) due to 7 false negative in micrometastases and 6 false negative in immunohistochemistry metastases. Positive predictive value was 75% due to a false positive diagnosis. However, specificity was acceptable (96%). Conclusions The high specificity of PET/CT imaging indicates that patients who have a PET-positive axilla should have an ALND rather than an SNB for axillary staging. In contrast, FDG-PET showed poor sensitivity in the detection of axillary metastases, confirming the need for SNB in cases where PET is negative in the axilla
Autores: Garcia-Velloso, Maria Jose; Coma, María Isabel; Peñuelas, Iván; et al.
Libro:  Medicina Nuclear en la práctica clínica
2012  págs. 295-305

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