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AIM: 125I-iododeoxyuridine is a potential Auger radiation therapy agent. Its incorporation in DNA of proliferating cells is enhanced by fluorodeoxyuridine. Here, we evaluated therapeutic activities of 125I-iododeoxyuridine in an optimized fluorodeoxyuridine pre-treatment inducing S-phase synchronization. METHODS: After S-phase synchronization by fluorodeoxyuridine, cells were treated with 125I-iododeoxyuridine. Apoptosis analysis and S-phase synchronization were studied by flow cytometry. Cell survival was determined by colony-forming assay. Based on measured growth parameters, the number of decays per cell that induced killing was extrapolated. RESULTS: Treatment experiments showed that 72 to 91% of synchronized cells were killed after 0.8 and 8 kBq/ml 125I-iododeoxyuridine incubation, respectively. In controls, only 8 to 38% of cells were killed by corresponding 125I-iododeoxyuridine activities alone and even increasing the activity to 80 kBq/ml gave only 42 % killing. Duplicated treatment cycles or repeated fluorodeoxyuridine pre-treatment allowed enhancing cell killing to >95 % at 8 kBq/ml 125I-iododeoxyuridine. About 50 and 160 decays per S-phase cells in controls and S-phase synchronization, respectively, were responsible for the observed cell killing at 0.8 kBq/ml radio-iododeoxyuridine. CONCLUSION: These data show the successful application of fluorodeoxyuridine that provided increased 125I-iododeoxyuridine Auger radiation cell killing efficacy through S-phase synchronization and high DNA incorporation of radio-iododeoxyuridine.
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Floxuridina/farmacología , Glioblastoma/patología , Glioblastoma/radioterapia , Apoptosis/efectos de la radiación , Línea Celular Tumoral , División del Núcleo Celular/efectos de los fármacos , División del Núcleo Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Glioblastoma/fisiopatología , Humanos , Dosis de RadiaciónRESUMEN
Echocardiography is the preferred initial test to assess cardiac morphology and ventricular function. Cardiac MRI enables an optimal visualisation of heart muscle without contrast injection, and precise measurement of the ventricular volumes and systolic function. It is therefore an ideal test for patients with poor echocardiographic windows or for the specific evaluation of right heart chambers. Heart CT also remarkably images heart muscle and precisely measures ventricular systolic function after intravenous injection of iodinated contrast. Coronary CT may also, in selected cases, avoid the need for diagnostic coronary angiography. Although very accurate, these imaging modalities are expensive and may be contra-indicated for a particular patient. Their use in clinical practice has to follow the accepted guidelines.
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Diagnóstico por Imagen , Corazón/diagnóstico por imagen , Miocardio/patología , Humanos , RadiografíaRESUMEN
The non-invasive evaluation of myocardial ischemia is a priority in cardiology. The preferred initial non-invasive test is exercise ECG, because of its high accessibility and its low cost. Stress radionuclide myocardial perfusion imaging or stress echocardiography are now routinely performed, and new non-invasive techniques such as perfusion-MRI, dobutamine stress-MRI or 82rubidium perfusion PET have recently gained acceptance in clinical practice. In the same time, an increasing attention has been accorded to the concept of myocardial viability in the decisional processes in case of ischemic heart failure. In this indication, MRI with late enhancement after intravenous injection of gadolinium and 18F-FDG PET showed an excellent diagnostic accuracy. This article will present these new imaging modalities and their accepted indications.
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Diagnóstico por Imagen/métodos , Isquemia Miocárdica/diagnóstico , HumanosRESUMEN
This clinical study was based on experimental results obtained in nude mice grafted with human colon carcinoma, showing that injected 131I-labeled F(ab')2 and Fab fragments from high affinity anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) gave markedly higher ratios of tumor to normal tissue localization than intact MAb. 31 patients with known colorectal carcinoma, including 10 primary tumors, 13 local tumor recurrences, and 21 metastatic involvements, were injected with 123I-labeled F(ab')2 (n = 14) or Fab (n = 17) fragments from MAb anti-CEA. The patients were examined by emission-computerized tomography (ECT) at 6, 24, and sometimes 48 h after injection using a rotating dual head scintillation camera. All 23 primary tumors and local recurrences except one were clearly visualized on at least two sections of different tomographic planes. Interestingly, nine of these patients had almost normal circulating CEA levels, and three of the visualized tumors weighed only 3-5 g. Among 19 known metastatic tumor involvements, 14 were correctly localized by ECT. Two additional liver and several bone metastases were discovered by immunoscintigraphy. Altogether, 86% of the tumor sites were detected, 82% with F(ab')2 and 89% with Fab fragments. The contrast of the tumor images obtained with Fab fragments suggests that this improved method of immunoscintigraphy has the potential to detect early tumor recurrences and thus to increase the survival of patients. The results of this retrospective study, however, should be confirmed in a prospective study before this method can be recommended for the routine diagnosis of cancer.
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Anticuerpos Monoclonales , Antígeno Carcinoembrionario/inmunología , Carcinoma/diagnóstico por imagen , Neoplasias del Colon/diagnóstico por imagen , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Neoplasias del Recto/diagnóstico por imagen , Adulto , Anciano , Carcinoma/inmunología , Neoplasias del Colon/inmunología , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/secundario , Neoplasias del Recto/inmunología , Estudios Retrospectivos , Neoplasias del Colon Sigmoide/diagnóstico por imagen , Neoplasias del Colon Sigmoide/inmunología , Tomografía Computarizada de Emisión/métodosRESUMEN
AIM: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated prospectively and compared with other known risk factors of relapse in early stage melanoma. METHODS: Surgery was guided by lymphoscintigraphy, blue dye and gamma probe detection. SLN were analysed by haematoxylin eosin (HE) histochemistry and multimarker immunohistochemistry (IHC). Disease free survival (DFS) was evaluated with Kaplan-Meier plots according to different parameters and Cox analyses of variance. RESULTS: From 210 patients a total of 381 SLN were excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow-up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for early relapse (p < 0.0005) were SLN positivity and a high Breslow index. CONCLUSION: SLN tumour positivity is an independent factor of high risk for early relapse with a higher power of discrimination than the Breslow index.
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Melanoma/patología , Biopsia del Ganglio Linfático Centinela , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
AIM: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. PATIENTS, METHODS: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. RESULTS: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65 +/- 10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p < 0.0001), followed by history of CAD (Hazard Ratio (HR) = 15.9; p = 0.0001), diabetic retinopathy (HR = 10.0; p = 0.001) and inability to exercise (HR = 7.7; p = 0.02). Patients with normal MPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. CONCLUSION: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a >5-fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients.
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Enfermedad Coronaria/diagnóstico por imagen , Angiopatías Diabéticas/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tecnecio Tc 99m Sestamibi , Radioisótopos de TalioRESUMEN
During one week, beginning 18 days after transplantation, nude mice bearing human colon carcinoma ranging from 115 to 943 mm3 (mean 335 mm3) were treated by repeated intravenous injections of either iodine-131-(131I) labeled intact antibodies or 131I-labeled corresponding F(ab')2 fragments of a pool of four monoclonal antibodies (MAbs) directed against distinct epitopes of carcinoembryonic antigen (CEA). Complete tumor remission was observed in 8 of 10 mice after therapy with F(ab')2 and 6 of the animals survived 10 mo in good health. In contrast, after treatment with intact MAbs, tumors relapsed in 7 of 8 mice after remission periods of 1 to 3.5 mo despite the fact that body weight loss and depression of peripheral white blood cells, symptoms of radiation toxicity, and the calculated radiation doses for liver, spleen, bone, and blood were increased or equal in these animals as compared to mice treated with F(ab')2.
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Anticuerpos Monoclonales/uso terapéutico , Antígeno Carcinoembrionario/inmunología , Neoplasias del Colon/radioterapia , Fragmentos Fab de Inmunoglobulinas/inmunología , Radioisótopos de Yodo/uso terapéutico , Animales , Anticuerpos Monoclonales/toxicidad , Antígeno Carcinoembrionario/toxicidad , Neoplasias del Colon/inmunología , Humanos , Fragmentos Fab de Inmunoglobulinas/toxicidad , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
Fifty-seven patients with suspected CEA-producing tumors were studied prospectively by radioimmunoscintigraphy (RIS) using a 123I-labeled anti-CEA monoclonal antibody (MAb) (essentially the F(ab')2 or Fab fragments) and emission computed tomography (ECT). Results of RIS were compared to those of a comprehensive diagnostic study. Final diagnosis was based on surgery, biopsy and autopsy (n = 39) or follow-up findings (n = 18). Three groups of patients were defined: Group A with suspected primary tumors (n = 11), Group B with probable (n = 19) and Group C with questionable (n = 27) tumor relapse. Eighty-eight per cent, 93% and 71% of the anatomic regions studied were correctly identified as being involved, and 97%, 97%, and 87% as being free from tumor in Groups A, B, and C, respectively. In the 27 patients from Group C with no definite diagnosis of relapse, and in whom diagnosis was most difficult, 38 tumor sites were involved. Of these, 21 were detected by both prospective RIS and repeated comprehensive study, six by RIS only and seven by conventional methods only. Four sites remained undetected by both approaches. Ten of the 21 lesions were detected by RIS more than 1 mo earlier than by any other method. Among the seven tumor sites detected by other diagnostic modalities only, three were identified at the time of RIS and four became positive more than 6 mo later. Overall diagnosis was entirely correct in 30, partially correct in 16 and incorrect in six patients studied. RIS with ECT and 123I-labeled anti-CEA MAb allows early detection of recurrence or metastasis of colorectal cancer. It thus contributes to reduced delay between diagnosis and treatment.
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Adenocarcinoma/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico por imagen , Abdomen/diagnóstico por imagen , Adenocarcinoma/patología , Adulto , Anciano , Anticuerpos Monoclonales , Antígeno Carcinoembrionario/inmunología , Neoplasias Colorrectales/patología , Femenino , Humanos , Radioisótopos de Yodo , Hígado/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pelvis/diagnóstico por imagen , Estudios Prospectivos , CintigrafíaRESUMEN
Technetium-99m ethyl cysteinate dimer (ECD) has high initial cerebral uptake with slow clearance in nonhuman primates suggesting ideal characteristics for single photon emission computer tomography (SPECT) imaging. We evaluated the biodistribution, dosimetry and scintigraphic pattern of [99mTc]ECD in normal subjects and the accuracy of SPECT imaging in patients with chronic cerebral infarction. Sixteen normal subjects were injected with approximately 10 mCi of [99mTc]ECD. Anterior and posterior single-pass whole-body images were obtained at multiple times after injection. Blood clearance of the radiotracer was rapid, falling to 10.0 +/- 6.6% and 4.9 +/- 1.1% of the injected dose at 2 and 60 min, respectively. Brain uptake was 6.4 +/- 2.1% of the injected dose 5 min after injection. The critical organ was the urinary bladder. Technetium-99m ECD SPECT was performed with a rotating gamma camera in ten of the 16 normal subjects and 34 patients with clinical and CT evidence of chronic stroke. Thirty-three of the thirty-four patients had focal [99mTc]ECD abnormalities on SPECT (97.1%) based on visual inspection of the SPECT images. In summary, we obtained high quality SPECT images as a result of the optimal physical and biologic characteristics of the tracer. Technetium-99m ECD SPECT shows promise for the evaluation of patients with stroke.
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Infarto Cerebral/diagnóstico por imagen , Cisteína/análogos & derivados , Compuestos Organometálicos , Compuestos de Organotecnecio , Tomografía Computarizada de Emisión , Infarto Cerebral/metabolismo , Enfermedad Crónica , Cisteína/farmacocinética , Femenino , Humanos , Masculino , Estudios Multicéntricos como Asunto , Compuestos Organometálicos/farmacocinética , Dosis de Radiación , Valores de Referencia , Distribución TisularRESUMEN
Of 10 patients with neuroblastoma who had both 123I-MIBG scintigraphy and MRI at diagnosis, four presented with bone marrow metastasis that was diagnosed by both imaging modalities and confirmed by bone marrow biopsy and smears. This report focuses on the follow up of the four patients with bone marrow metastasis. MIBG scintigraphy and MRI were concordant in two patients, a case of normalization and a case of relapse in the seventh dorsal vertebra confirmed by surgical biopsy. The last two patients presented a normalized MIBG scan for marrow infiltration after chemotherapy but persistent abnormal MRI signal of several vertebrae, suggesting marrow infiltration, up to 27 mo after the end of chemotherapy in one case. In the second patient, MRI bone marrow aspect returned to normal 4 mo after the end of chemotherapy. Bone marrow biopsy remained negative in these two MIBG-negative patients. These cases suggest that in presence of complete normalization of the MIBG scan after chemotherapy, the persistence of a hypointense signal on bone marrow on T1WI does not necessarily indicate persistence of disease but may be due to delayed normalization. Therefore, attention must be paid to the delay of signal normalization on MRI (which can be as long as more than 2 yr after the end of chemotherapy) in order to avoid false-positive interpretation.
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Neoplasias de la Médula Ósea/diagnóstico por imagen , Neoplasias de la Médula Ósea/secundario , Radioisótopos de Yodo , Yodobencenos , Imagen por Resonancia Magnética , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/secundario , 3-Yodobencilguanidina , Neoplasias de la Médula Ósea/diagnóstico , Niño , Preescolar , Humanos , Masculino , Neuroblastoma/diagnóstico , CintigrafíaRESUMEN
Cardiac function and left ventricular dynamics were measured in seven consecutive patients 1 day before and 6 months after percutaneous transluminal balloon angioplasty of subtotal proximal stenosis of the left anterior descending coronary artery. Before angioplasty all patients had obvious left ventricular dysfunction during exercise and to a smaller degree during isoproterenol infusion; the condition of all patients was greatly improved 6 months after angioplasty. After angioplasty, left ventricular end-diastolic pressure was normal at rest and decreased from a mean (+/- standard error of the mean) of 33.8 +/- 1.6 to 19.2 +/- 0.5 mm Hg on exercise. Left ventricular ejection fraction, measured by a gated blood pooling technique with technetium-99m, improved on exercise from 46 +/- 5.0 percent to 69 +/- 1.0 percent. Cardiac output and stroke volume index increased significantly with exercise after angioplasty. The peak negative rate of pressure reduction in the left ventricle (dP/dt/min), an index of left ventricular relaxation, was highly abnormal on exercise before (2,307 +/- 260 mm Hg/s) and increased to the normal range (3,154 +/- 200 mm Hg/s) after angioplasty. The improvement in left ventricular function after transluminal angioplasty in these cases of proximal left anterior descending coronary arterial stenosis is extremely encouraging.
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Enfermedad Coronaria/cirugía , Vasos Coronarios/cirugía , Contracción Miocárdica , Adulto , Gasto Cardíaco , Cateterismo , Ventrículos Cardíacos/fisiopatología , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Despite major progress made during the past 25 years in the genetic engineering and labeling of monoclonal antibodies (Mab) and in the understanding of the uptake and kinetics of radiolabeled Mab by normal and tumor tissues, immunoscintigraphy never succeeded in becoming a routine procedure, compared with a bone or gallium scan. The more and more generalized availability of positron emission tomography (PET) with Fluorine-18 fluorodeoxyglucose (FDG) for diagnosis and staging of malignant diseases will probably definitively seal the fate of radioimmunodiagnosis as it has been conceived up until now. With respect to the nonspecificity of deoxyglucose uptake by tumor cells, it is not to be excluded that antibodies, or more likely antibody fragments, labeled with positron emitters might be used for tissue characterization. The recent success of radioimmunotherapy, especially in B-cell malignancies, entitles us to expect that RIT will become part of standard therapy of patients with malignancies. In that case, immunoscintigraphy will be needed for treatment planning (patient selection and dosimetry). One might even speculate that the oncologists who are becoming familiar with nuclear medicine tracer techniques for pretreatment evaluation might be interested in extending them to distribution and kinetic studies of other cytotoxic drugs. The close cooperation between nuclear medicine specialists, oncologists, and hematologists is essential to make radioimmunotherapy a routine procedure.
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Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Radioinmunodetección , Radioinmunoterapia , Anticuerpos Monoclonales , Fluorodesoxiglucosa F18 , Humanos , Radiofármacos/uso terapéutico , Tomografía Computarizada de EmisiónRESUMEN
Immunoscintigraphy offers the possibility of specifically targeting human tumors, but the complexity of the human immune system, as well as tumor-related phenomena, prevent monoclonal antibodies from reaching a large number of tumor cells in which they can interact with the antigen. Possible ways to overcome these problems are the use of small fragments, in particular those of genetically engineered humanized antibodies including single immunoglobulin-variable domains, as well as techniques to label the antibody in vivo after a sufficient amount has been taken up by the tumor and the remainder has been eliminated. Despite the low absolute tumor uptake, results of European studies, presently available radiolabeled monoclonal antibodies in gastrointestinal and ovarian cancers yield an average sensitivity of more than 70% with an average specificity of more than 80%, even in otherwise occult tumors. Because of possible tracer uptake in normal liver, the detection rate of liver metastases varies from less than 10% to more than 90%. For the detection of local recurrence in the pelvis, immunoscintigraphy has been found to be more accurate than methods that are based on the imaging of structural changes. Fusion of morphological and functional images might improve the early detection of recurrent and metastatic disease. In melanoma, another tumor that has been extensively studied in Europe, similar results have been obtained, whereas only few data are presently available for other tumors (especially lung and breast cancer).
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Neoplasias/diagnóstico por imagen , Radioinmunodetección , Animales , Europa (Continente) , Femenino , Historia del Siglo XX , Humanos , Masculino , Radioinmunodetección/historia , Radioinmunodetección/métodos , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión de Fotón Único , Estados UnidosRESUMEN
Comprehensive evaluation of renal transplants has been important in differential diagnosis of medical and surgical complications in the early post-transplantation period and in the long-term follow-up. If performed well, it yields excellent functional and good anatomic information about the graft that can be effectively used in the patient. That includes selection of patients for biopsy and for various drug regimens. This is true especially in patients with anuric acute tubular necrosis (ATN) and in patients with developing chronic rejection. Improving indices of renal function (effective renal plasma flow, uptake of tubular tracers) can indicate resolution of tubular injury (ATN) while there is still no improvement in plasma creatinine. In patients with chronic rejection, plasma creatinine increases only after approximately 30% of renal function is lost due to graft fibrosis. Early recognition of this condition could permit treatment and delay of retransplantation. The protocol recommended at the Copenhagen meeting includes a flow study, scintigram of the kidneys, prevoid and postvoid bladder image, injection site image (quality control), time/activity curves of the graft and bladder, and quantitative data of perfusion, function, and tracer transit. The flow study obtained during the initial transit of the bolus through the graft could be performed either with 99mTc mercaptoacetyltriglycine, or 99mTc diethylenetriaminepentaacetate (DTPA). Quantitative analysis of perfusion facilitates interpretation of the study during the early post-transplantation period. ATN, common in cadaver transplants, typically shows adequate perfusion. The function phase should include images and time/activity curves. Images alone are insufficient. Quantitative data such as clearance or other indices of function and indices of tracer transit are essential for correct interpretation of the results. Normal images and normal graft function reliably exclude clinically important complications. A single scintigram demonstrating prolonged tracer transit with decreased function cannot separate acute rejection and ATN. On serial studies, decline in function and poor perfusion are indicative of acute rejection. A normally appearing scintigram without cortical retention, but with low function, is consistent with chronic rejection. Pharmacological intervention to exclude obstruction (diuretic renogram) or hemodynamically significant renal artery stenosis (angiotensin converting enzyme challenge) should be used whenever indicated.
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Trasplante de Riñón/diagnóstico por imagen , Riñón/diagnóstico por imagen , Renografía por Radioisótopo/normas , Inhibidores de la Enzima Convertidora de Angiotensina , Diuréticos , Fibrosis , Estudios de Seguimiento , Rechazo de Injerto , Humanos , Interpretación de Imagen Asistida por Computador , Procesamiento de Imagen Asistido por Computador , Necrosis Tubular Aguda/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Renografía por Radioisótopo/métodos , Flujo Plasmático Renal Efectivo , Pentetato de Tecnecio Tc 99mRESUMEN
The role of cholecystokinin (CCK) in the regulation of gastric emptying of physiological meals containing solids and liquids in humans remains controversial. We studied the role of endogenous CCK in the emptying of a solid/liquid meal administering the new, highly specific and potent CCK-A receptor antagonist lintitript. Gastric emptying was assessed in nine healthy male volunteers using a randomized, double blind, two-period crossover design with oral lintitript (15 mg 1 h prior to meal intake) or placebo on two different days. After ingestion of a pancake (570 kcal) labelled with 500 microCi of 99mTc-sulfur colloid and 500 ml 10% dextrose containing 80 microCi. 111In-DTPA, subjects were studied in a sitting position, using a dual-headed gamma camera. Plasma CCK and pancreatic polypeptide (PP) were measured by a specific RIA. Lintitript distinctly accelerated gastric emptying of solids, while gastric emptying of liquids was not significantly altered. The lag period was shortened by 20% (P<0.05), AUC and half emptying time of solid emptying were lowered by 12% and 13%, respectively (P<0.03). Lintitript markedly increased postprandial plasma CCK release (P<0.001) while distinctly reducing postprandial PP levels (P<0.01) as compared to placebo. These data provide further evidence for a significant role of CCK in the regulation of gastric emptying of solids. The study demonstrates for the first time the marked gastrokinetic properties of the new CCK-A receptor antagonist lintitript in humans.
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Vaciamiento Gástrico , Ácidos Indolacéticos/farmacología , Receptores de Colecistoquinina/antagonistas & inhibidores , Tiazoles/farmacología , Adulto , Colecistoquinina/sangre , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Polipéptido Pancreático/sangre , Receptor de Colecistoquinina ARESUMEN
Radioimmunotherapy (RIT) represents an exciting new therapeutic option for the treatment of B-cell non-Hodgkin's lymphoma (NHL), emerging at a time when significant advances have been made in NHL classification, molecular genetics and treatment. Despite recent treatment advances, including the use of fludarabine phosphate-based combination chemotherapies, able to eradicate minimal residual disease, there remains much room for improvement. The incorporation of RIT into treatment schedules is an attractive option to exploit the extreme sensitivity of lymphoma cells to irradiation. In this supplement, we examine the potential future roles for RIT in the light of past and present therapies, existing RIT clinical data and the unique attributes of radiolabeled monoclonal antibodies.
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Linfoma de Células B/terapia , Algoritmos , Antineoplásicos/uso terapéutico , Humanos , Linfoma de Células B/clasificación , Radioinmunoterapia/métodosRESUMEN
AIMS: Patients with non-resectable soft tissue sarcomas of the extremities do not live longer if they are treated by amputation or disarticulation. In order to avoid major amputations, we tested isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF)+melphalan+/-interferon-gamma (IFN) as a pre-operative, neoadjuvant limb salvage treatment. METHODS: Twenty-two patients were included (six men and 16 women; three upper limb and 19 lower limb tumours). The AJCC stage was IIA in four patients, III in seven and IV in 11. Thirteen cases were recurrent or progressive after previous therapy; five tumours had a diameter >/=20 cm, and four were multiple or regionally metastatic. There were six malignant fibrous histiocytomas, five liposarcomas, four malignant peripheral nerve sheath tumours, three rhabdomyosarcomas, two leiomyosarcomas, one recurrent extraskeletal osteosarcoma and one angiosarcoma. RESULTS: Twenty-four ILPs were performed in the 22 patients, and 18 (82%) experienced an objective response: this was complete in four (18%) and partial in 14 (64%). Three patients had a minimal or no response and the tumour progressed in one case. All patients had fever for 24 hours but only one developed a reversible grade 3 distributive shock syndrome with no sequelae. There was no grade 4 toxicity. Seventeen patients (77%) underwent limb-sparing resection of the tumour remnants after a median time of 3.4 months: 10 resections were intracompartmental and seven extracompartmental. Surgery included flaps or skin grafts in five patients, arterial replacement in two and knee arthrodesis in one. Adjuvant chemotherapy was given to eight patients and radiotherapy to six. In one patient amputation was necessary after a second ILP. Secondary amputations were performed for recurrence in two patients, resulting in an overall limb salvage rate of 19/22 (86%). After a median follow-up of 18.7 months, 10 recurrences were recorded: seven were both local and systemic and three were only local. The median disease free and overall survival times have been >12.5 and 18.7 months respectively: this is similar to the outcome after primary amputations for similar cases. CONCLUSION: ILP with TNF and chemotherapy is an efficient limb sparing neoadjuvant therapy for a priori non-resectable limb soft tissue sarcomas.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Pierna/cirugía , Sarcoma/tratamiento farmacológico , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/cirugía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Quimioterapia del Cáncer por Perfusión Regional , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Interferón gamma/administración & dosificación , Interferón gamma/efectos adversos , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/cirugía , Radioterapia Adyuvante , Terapia Recuperativa , Sarcoma/radioterapia , Neoplasias de los Tejidos Blandos/radioterapia , Análisis de Supervivencia , Factor de Necrosis Tumoral alfa/administración & dosificación , Factor de Necrosis Tumoral alfa/efectos adversosRESUMEN
Various preparations of anti-CEA antibodies have shown to detect very sensitively CEA producing tumors. The development of human anti-mouse antibodies (HAMA) prevents from the widespread use of immunoscintigraphy (IS) in the follow-up of patients with colorectal carcinoma. It is, however, not yet clear if genetically reshaped antibodies will solve this problem and it is even less clear if this will change prognosis of these patients. There is certainly room for new therapeutic approaches in colorectal carcinoma. Radioimmunotherapy in combination with other techniques might advantageously complete surgery, chemotherapy and radiotherapy, but needs to be further developed.
Asunto(s)
Antígeno Carcinoembrionario/inmunología , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Radioinmunodetección/métodos , Radioinmunoterapia/métodos , HumanosRESUMEN
A total of 226 patients was studied in a phase-III multicenter trial to compare the results of stress/rest 99mTc-MIBI with 201TI scintigraphy and/or coronary arteriography. The evaluation of planar and SPECT imaging was based on a semiquantitative visual scoring. A congruent diagnosis was generated from all planar 201TI and 99mTc-MIBI scintigrams performed in 36 patients. In 62 of 63 patients, SPECT-studies with 99mTc-MIBI and 201TI led to an identical diagnosis. In one patient a positive result was obtained with 201TI-SPECT whereas 99mTc-MIBI was negative. Segmental agreement for 1509 SPECT segments was 85.7%, for 554 planar segments it was 86.6%. In comparison to coronary arteriography, performed in 180 patients, the overall sensitivity for the correct diagnosis of coronary artery disease (CAD) was 86% for planar MIBI scintigraphy or 92% for MIBI-SPECT. Overall specificity was 100% for planar imaging and 57% for SPECT. The low specificity of MIBI-SPECT was probably due to high prevalence of CAD in this study population. In a subgroup of 43 patients, who underwent coronary angiography, identical results were found with 99mTc-MIBI and 201TI. Only one patient showed a positive scintigraphic result with both 99mTc-MIBI and 201TI without angiographically proven stenosis greater than 50% or prior myocardial infarction. Vessel sensitivities in stenosed coronary arteries (greater than 50% stenosis) were 54% for the LAD and 87% for the RCX/RCA areas with MIBI-SPECT, or 51% or 79% for planar scintigraphy, respectively. Vessel specificities for SPECT were 65% in the LAD or 52% in the RCX/RCA, or 90% or 83% in planar imaging.(ABSTRACT TRUNCATED AT 250 WORDS)