RESUMEN
PURPOSE: The αvß3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvß3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with ß(-) emitters in a nude mouse model of αvß3 integrin-expressing tumours. METHODS: Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvß3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvß3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvß3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. RESULTS: Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvß3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvß3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvß3-negative tumours. CONCLUSION: (90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvß3-expressing tumours for internal targeted radiotherapy.
Asunto(s)
Integrina alfaVbeta3/metabolismo , Lutecio/uso terapéutico , Péptidos Cíclicos , Radiofármacos/uso terapéutico , Radioisótopos de Itrio/uso terapéutico , Animales , Línea Celular Tumoral , Humanos , Integrina alfaVbeta3/genética , Lutecio/efectos adversos , Lutecio/farmacocinética , Ratones , Ratones Desnudos , Neoplasias Experimentales/genética , Neoplasias Experimentales/radioterapia , Péptidos Cíclicos/efectos adversos , Péptidos Cíclicos/farmacocinética , Radiofármacos/efectos adversos , Radiofármacos/farmacocinética , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto , Radioisótopos de Itrio/efectos adversos , Radioisótopos de Itrio/farmacocinéticaRESUMEN
Our aim was to analyse whether biomarkers extracted from baseline 18F-FDG PET before anti-PD1 treatment contribute to prognostic survival information for early risk stratification in metastatic melanoma. Fifty-six patients, without prior systemic treatment, BRAF wild type, explored using 18F-FDG PET were included retrospectively. Our primary endpoint was overall survival (OS). Total metabolic tumoral volume (MTV) and forty-one IBSI compliant parameters were extracted from PET. Parameters associated with outcome were evaluated by a cox regression model and when significant helped build a prognostic score. Median follow-up was 22.1 months and 21 patients died. Total MTV and long zone emphasis (LZE) correlated with shorter OS and served to define three risk categories for the prognostic score. For low, intermediate and high risk groups, survival rates were respectively 91.1% (IC 95 80-1), 56.1% (IC 95 37.1-85) and 19% (IC 95 0.06-60.2) and hazard ratios were respectively 0.11 (IC 95 0.025-0.46), P = 0.0028, 1.2 (IC 95 0.48-2.8), P = 0.74 and 5.9 (IC 95 2.5-14), P < 0.0001. To conclude, a prognostic score based on total MTV and LZE separated metastatic melanoma patients in 3 categories with dramatically different outcomes. Innovative therapies should be tested in the group with the lowest prognosis score for future clinical trials.
Asunto(s)
Inmunoterapia , Melanoma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptor de Muerte Celular Programada 1/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Fluorodesoxiglucosa F18 , Humanos , Inmunoterapia/métodos , Inmunoterapia/mortalidad , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Carga TumoralRESUMEN
The aim of this 3-month follow-up prospective pragmatic study was to evaluate the implementation of a pulmonary embolism (PE) diagnostic strategy in clinical practice. One thousand and one hundred thirty-four consecutive in- and outpatients with clinically suspected PE were enrolled into a sequential diagnostic algorithm in which vascular medical unit plays a pivotal role in advising physicians and suggesting the most appropriate tests according to the diagnostic algorithm. In this observational study, patients that followed the proposed work-up were attributed to a so-called "conform group". Patients in whom diagnostic work-up was not according to protocol were attributed to a "non-conform group". Nine hundred and ninety-seven patients (87.9%) had a conform work-up, and 137 patients a non-conform work-up according to the proposed diagnostic algorithm. The non-conform work-up directly increased in relation to the age of the referred patients. PE was ruled out in 907 (80%) patients of whom 787 (86.8%) were in the conform group. Of the 797 patients who did not receive anticoagulant drugs, follow-up was obtained in 792 (99.4%). Among these patients, the incidence of acute thromboembolic events during the 3-month follow-up period was different in the group of patients that had a conform work-up (1%, [95% CI, 0.5-2.1%]) from the non-conform group patients (4.5%, [95% CI, 2-10.2%]. Therefore patients from the non-conform group have an independent increased risk to develop a thromboembolic event during the follow-up, adjusted odds ratio 3.3 [1.1-10, 95% CI]. Therefore we demonstrated that a non-conform diagnostic management strategy is associated with a higher risk of thrombotic event occurrence.
Asunto(s)
Algoritmos , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico , Trombosis/epidemiología , Trombosis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Árboles de Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
High hematological toxicity has been observed with anti-carcinoembryonic antigen radioimmunotherapy (RIT) in medullary thyroid carcinoma (MTC), suggesting metastatic bone involvement (BI). This retrospective study evaluated the rate of BI in MTC patients enrolled in two phase-I/II RIT trials using anti-carcinoembryonic antigen x anti-diethylenetriamine pentaacetic acid bispecific antibodies and [(131)I]di-diethylenetriamine pentaacetic acid hapten. Thirty-five patients underwent bone scintigraphy, bone magnetic resonance imaging (MRI), and post-RIT immunoscintigraphy (IS). IS performed in MTC patients was compared with IS conducted in 12 metastatic colorectal carcinoma (CRC) patients. Quantitative analysis of bone uptake was performed in three MTC and three CRC patients. In the MTC group, bone scintigraphy detected BI in 56.6% of patients, MRI in 75.8%, and IS in 88.6%. BI was confirmed by undirected (random) bone marrow biopsy, by bone surgery, or by two positive imaging methods in 74.3% of the patients. Sensitivity per patient of bone scintigraphy, MRI, and IS were 72.7, 100, and 100%, respectively. In contrast, IS visualized BI in only 33.3% of CRC patients; bone uptake was lower in CRC than in MTC patients. Bone MRI combined with post-RIT IS disclosed a much higher BI rate in advanced MTC than previously reported in the literature.
Asunto(s)
Médula Ósea/patología , Huesos/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radioinmunoterapia , Estudios Retrospectivos , Neoplasias de la Tiroides/radioterapiaRESUMEN
As small cell lung carcinoma (SCLC) is frequently a widespread disease at diagnosis, highly radiosensitive and often only partially responsive to chemotherapy, radioimmunotherapy (RIT) would appear to be a promising technique for treatment. We report the preliminary results of a Phase I/II trial of RIT in SCLC using a two-step method and a myeloablative protocol with circulating stem cells transplantation. Fourteen patients with proved SCLC relapse after chemotherapy were treated with RIT. They were first injected i.v. with a bispecific (anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid) monoclonal antibody (20-80 mg in 100 ml of saline solution) and then 4 days later with di-(In-diethylenetriaminepentaacetic acid)-tyrosyl-lysine hapten labeled with 1.48-6.66 GBq (40-180 mCi) of I-131 and diluted in 100 ml of saline solution. In patients receiving 150 mCi or more, circulating stem cells were harvested before treatment and reinfused 10-15 days later. Treatment response was evaluated by CT and biochemical data during the month before and 1, 3, 6, and 12 months after treatment. All patients received the scheduled dose without immediate adverse reactions to bispecific antibody or 1-131 hapten. Toxicity was mainly hematological, with two cases of grade 2 leukopenia and three cases of grade 3 or 4 thrombopenia. Body scanning 8 days after injection of the radiolabeled hapten generally showed good uptake at the tumor sites. Estimated tumor dose was 2.6-32.2 cGy/mCi. Among the 12 patients evaluated to date, we have observed 9 progressions, 2 partial responses (one almost complete for 3 months), and 1 stabilization of more than 24 months. Efficiency and toxicity were dose-related. The maximal tolerable dose without hematological rescue was 150 mCi. These preliminary results are encouraging, and dose escalation is currently continuing to reach 300 mCi. RIT should prove to be an interesting therapeutic method for SCLC, although repeated injections and hematological rescue will probably be required, as well as combination with other treatment modalities.
Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antígeno Carcinoembrionario/inmunología , Carcinoma de Células Pequeñas/radioterapia , Haptenos/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias Pulmonares/radioterapia , Ácido Pentético/inmunología , Radioinmunoterapia , Anciano , Animales , Anticuerpos Antiidiotipos/sangre , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Dosificación RadioterapéuticaRESUMEN
The toxicity and therapeutic efficacy of escalating doses of anti-carcinoembryonic antigen x anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid)-In bispecific monoclonal antibody (F6-734) and iodine 131-labeled bivalent hapten were determined in a Phase I/II trial. A total of 26 patients with recurrences of medullary thyroid cancer documented by imaging and a rise in serum thyrocalcitonin were enrolled. Twenty to 50 mg of F6-734 and 40-100 mCi of 131I-hapten were injected 4 days apart. Quantitative scintigraphy was performed after the second injection for dosimetry estimations in eight cases. Clinical, biological, and morphological follow-up was carried out for 1 year after treatment. The mean percentage of injected activity per gram of tumor at the time of maximum uptake was 0.08% (range, 0.003-0.26%). The tumor biological half-life ranged from 3 to 95 days, and tumor doses ranged from 2.91 to 184 cGy/mCi. The estimated tumor-to-nontumor dose ratios were 43.8 x 53.4, 29.6 x 35.3, 10.9 x 13.6, and 8.4 x 10.0 for total body, red marrow, liver, and kidney, respectively. Grade III/IV hematological toxicity was observed in seven patients, most of them with bone metastases. Among the 17 evaluable patients, 4 pain reliefs, 5 minor tumor responses, and 4 biological responses with decrease of thyrocalcitonin were observed. Nine patients developed human anti-mouse antibody. Dose-limiting toxicity was hematological, and maximum tolerated activity was 48 mCi/m2 in this group of patients, most of whom had suspected bone marrow involvement. The therapeutic responses observed in patients mainly with a small tumor burden are encouraging for the performance of a Phase II trial with minimal residual disease.
Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Carcinoma Medular/radioterapia , Haptenos/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Radioinmunoterapia , Neoplasias de la Tiroides/radioterapia , Adolescente , Adulto , Anciano , Anticuerpos Antiidiotipos/sangre , Anticuerpos Biespecíficos/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoterapia/efectos adversos , Dosificación RadioterapéuticaRESUMEN
The only current possibility for curing medullary thyroid carcinoma (MTC), especially recurrences, is total surgical removal. Early positive diagnosis of recurrences is now possible by monitoring tumor markers such as thyrocalcitonin and carcinoembryonic antigen (CEA). However, preoperative topographic diagnosis of such recurrences remains an unresolved problem. Immunoscintigraphy (IS) using an anti-CEA monoclonal antibody is a new approach that complements morphological imaging, i.e. ultrasonography, computerized tomography, and magnetic resonance imaging. In this study, IS by means of an 111In-labeled anti-CEA monoclonal antibody F(ab')2 was performed nine times in eight patients. True positives were obtained five times (one case of cervical involvement confirmed by surgery, three cases of mediastinal involvement confirmed by computerized tomography, magnetic resonance imaging, and surgery, and one case of bone metastasis, one of them was revealed neither by x-ray nor by conventional bone scan). The remaining four tests gave a false positive, a true negative, a probably false negative, and one unconclusive result. We conclude that IS is helpful in diagnosing sites of MTC recurrence and should accompany other examinations in the evaluation of lesions.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígeno Carcinoembrionario/inmunología , Carcinoma/diagnóstico por imagen , Fragmentos Fab de Inmunoglobulinas , Radioinmunodetección , Neoplasias de la Tiroides/diagnóstico por imagen , Adulto , Femenino , Humanos , Radioisótopos de Indio , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Periodo PosoperatorioRESUMEN
28 patients with primitive lung cancers were imaged by immunoscintigraphy (IS) with 111indium-labelled F(ab')2 anti-carcinoembryonic antigen (CEA), to assess this technique for mediastinal staging. IS revealed primitive tumours in 21 cases in whom mediastinal extension was assessed. There was concordance between clinical staging and IS confirmed by surgery in 17 cases, and discordance in 4. After surgery, discordance was in favour of IS in 2 cases (1 true positive and 1 true negative) and in favour of clinical staging in 2 (false positive of immunoscintigraphy). Anti-CEA IS could be useful for improving mediastinal staging of lung cancer.
Asunto(s)
Antígeno Carcinoembrionario/inmunología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Radioisótopos de Indio , Neoplasias Pulmonares/diagnóstico por imagen , Radioinmunodetección , Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Fragmentos Fab de Inmunoglobulinas , Neoplasias Pulmonares/patología , Estadificación de NeoplasiasRESUMEN
An important criterion for the clinical use of a new imaging technique is the correct reproducibility of interpretation. Forty-six paired immunoscintigraphic examinations were performed on 43 patients with suspected ovarian carcinoma recurrence using F(ab')2 fragments of OC125 antibody labeled first with indium-111 and then with iodine-131. Planar scintigraphy (PS) and emission computed tomography (ECT) images were interpreted blindly and separately by three observers, and reproducibility was evaluated by a kappa concordance index. Intra- and interobserver reproducibility were generally satisfactory (kappa values of 0.6 and 0.7, respectively). Binomial analysis of kappa values for ECT showed the superiority of indium-111 for intraobserver (p = 0.035) and interobserver (p = 0.0039) study. However, for PS there was no significant difference in reproducibility with the two radionuclides.
Asunto(s)
Anticuerpos Monoclonales , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Carbohidratos Asociados a Tumores/inmunología , Femenino , Humanos , Radioisótopos de Indio , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Variaciones Dependientes del Observador , Neoplasias Ováricas/inmunología , Reproducibilidad de los Resultados , Tomografía Computarizada de EmisiónRESUMEN
UNLABELLED: Immunoscintigraphy (IS) using anti-CEA F(ab')2 monoclonal antibody (MAb) is useful for improving mediastinal staging of nonsmall cell lung cancer (NSCLC), but the technique was limited because of an insufficient contrast between tumor and normal tissues. The aim of this study was to determine if the method could be improved by a two-step method which uses a bispecific anti-CEA/anti-di-DTPA antibody (Bs-MAb) and 111In-labeled di-DTPA-tyrosyl-lysine bivalent hapten. METHODS: Twelve patients were intravenously given a 30 min Bs-MAb infusion (0.1 mg/kg). Four days later, they were injected intravenously with 0.1 microgram/kg hapten labeled with 185 MBq 111In (5 mCi). Images were recorded immediately and 6 and 24 hr after hapten injection. A pharmacokinetic analysis was performed. Surgery was performed 3 days after 111In-hapten injection, and samples of tumor and normal tissues were collected for immunohistochemical and biodistribution studies. IS results were classified as true-positive (TP), false-positive (FP), true-negative (TN) or false-negative (FN) according to the surgical data. RESULTS: Primary tumors were visualized in nine patients. The contrast was excellent, generally higher than that obtained with direct labeling of anti-CEA. In the mediastinum, IS results were (after surgery) five TN, two TP and one FP. One case remains undetermined. The FP result was due to a Bs-MAb uptake in intrapulmonary lymph nodes. IS was in agreement with preoperative staging in six of these nine patients and discordant in three. CONCLUSION: Our study confirmed that the two-step method with a bispecific antibody could greatly improve the performances of IS for lung cancer staging.
Asunto(s)
Anticuerpos Biespecíficos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Haptenos , Radioisótopos de Indio , Neoplasias Pulmonares/diagnóstico por imagen , Ácido Pentético , Radioinmunodetección/métodos , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/inmunología , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Mediastino/diagnóstico por imagen , Estadificación de Neoplasias , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: Pretargeting labeled bivalent hapten with bispecific antibodies has proven feasible in the clinic, and our earlier results have suggested the technique may be very sensitive for detecting small recurrences and metastases. Medullary thyroid carcinoma (MTC) is an example where this technique may be the most useful since local recurrences and isolated metastases are removed surgically when detected, and thyrocalcitonin provides a specific and sensitive tumor marker. In our current study, we evaluated pretargeted immunoscintigraphy in a larger number of MTC patients. METHODS: Anti-carcinoembryonic antigen (CEA) x anti-diethylenetriaminepentaacetic acid (DTPA) indium bispecific antibody and 111In-labeled bivalent DTPA hapten were administered sequentially (4-5 days apart) to 44 patients with elevated circulating calcitonin after resection of primary MTC. Immunoscintigraphy was performed 2, 5 and 24 hr after hapten injection and, when necessary, at longer time intervals. When available, a handheld gamma probe was used during surgery. RESULTS: Fifteen patients had known tumor sites before immunoscintigraphy. Tumors were imaged in 12 (80%) of these patients, including 3 with liver metastases. Five unknown tumor sites were detected. For the 29 patients with occult disease, immunoscintigraphy detected high-activity uptake sites in 21 patients (72%), including 5 in the liver. Twelve were confirmed by surgery, 1 by guided morphologic imaging and 1 by venous catheterization. There were 2 false-positive patients. The other 5 patients have not yet been confirmed. All detected liver metastases were high-activity uptake areas. Radioimmunoguided surgery was used in 14 patients. It was considered helpful by the surgeon in 12 patients, including 4 patients where it determined the resection of small, not palpable nor visible, tumor-involved lymph nodes. Surgical resection resulted in a significant decrease (8 patients) or normalization (1 patient) of circulating calcitonin and CEA. CONCLUSION: This technique affords high sensitivity and specificity for detecting small tumor lesions including liver metastases. Its use for immunoscintigraphy and guided surgery should improve the therapeutic management of recurrent MTC.
Asunto(s)
Anticuerpos Biespecíficos , Carcinoma Medular/diagnóstico por imagen , Haptenos , Radioisótopos de Indio , Radioinmunodetección/métodos , Neoplasias de la Tiroides/diagnóstico por imagen , Adulto , Anciano , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/inmunología , Carcinoma Medular/secundario , Carcinoma Medular/cirugía , Femenino , Humanos , Cuidados Intraoperatorios , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Ácido Pentético , Cintigrafía/instrumentación , Sensibilidad y Especificidad , Neoplasias de la Tiroides/cirugíaRESUMEN
CEA, SCC and CYFRA 21-1 were measured in samples of serum coming from 105 'Non small cell lung cancer' (NSCLC) patients. The present study has been carried out to compare these markers, to analyse their prognostic significance and to determine the best combination of tumor markers. The median value and interquartile range were: CYFRA 21-1: 2,3 ng/ml, CEA: 3,7 ng/ml, SCC: 1,2 ng/ml. CEA demonstrated higher values in adenocarcinomas (P = 0.04). SCC and CYFRA 21-1 were comparable in the different histologic groups. CYFRA 21-1 and CEA values were dependant on tumor stage. Advanced tumors (T3 and T4) demonstrated higher serum CYFRA 21-1 level (P = 0.0006). CYFRA 21-1 was higher than 3,3 ng/ml in 36% of patients. CEA was higher than 5 ng/ml in 38% of patients and SCC was higher than 2 ng/ml in 27% of patients. Patients with a high CEA and CYFRA21-1 serum level had a shorter survival than those with a normal serum level. In a Cox regression analysis four variables (TNM stage, age, CYFRA 21-1 and CEA level) were found to be significant in the prediction of survival; CYFRA 21-1 level had the lowest P value (P = 0.0002). The current study suggests the use of a combination of CEA and CYFRA 21-1 in the clinical care of NSCLC.
Asunto(s)
Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Queratinas/sangre , Neoplasias Pulmonares/sangre , Serpinas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Queratina-19 , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
The plasma levels of tumor necrosis factor were measured during a longitudinal survey of 84 subjects living in an endemic area of malaria. In most cases, the plasma tumor necrosis factor was found at its highest level during the malaria transmission peak and became normal again during the dry season. Children having suffered from malarial attack keep low tumor necrosis factor levels compared to adults and asymptomatic children. These results suggest that tumor necrosis factor could be associated with the development of resistance against malaria.
Asunto(s)
Malaria/transmisión , Factor de Necrosis Tumoral alfa/análisis , Adolescente , Adulto , Niño , Preescolar , Cloroquina/uso terapéutico , Femenino , Humanos , Estudios Longitudinales , Malaria/epidemiología , Masculino , Radioinmunoensayo , Factores de TiempoRESUMEN
Antisense oligodeoxynucleotides (ODNs) have great promise for therapy. Oligomers labeled with gamma-emitting radioelements have great promise for diagnosis. These radiolabeled oligomers can be used to identify the presence of a particular messenger RNA through simple external detection of radioactivity by means of scintigraphy. This review evaluates the progress in the development of antisense oligodeoxynucleotides for non-invasive imaging of chemoresistance. As nominated by H.N. Wagner at the final session of Nuclear Medicine congress in Denver, the deoxyribonucleic acid is "the molecule of the millennium".
Asunto(s)
Neoplasias/tratamiento farmacológico , Oligonucleótidos Antisentido/uso terapéutico , Radioisótopos/química , Humanos , Oligonucleótidos Antisentido/químicaRESUMEN
The pretargeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that AES can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising.
Asunto(s)
Neoplasias/radioterapia , Radioinmunoterapia/métodos , Animales , Anticuerpos Biespecíficos/farmacocinética , Anticuerpos Biespecíficos/uso terapéutico , Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Neoplasias/diagnóstico por imagen , Radioinmunodetección , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapiaRESUMEN
Monoclonal antibodies labeled with a radionuclide make feasible the in vivo radioimmunotargeting of tumor cells. This targeting could be performed for diagnosis, using gamma emitters, or for therapeutic purpose when antibodies are labeled with beta- and in the future alpha-emitters. Diagnosis applications (tumor detection and caracterization), i.e. immunoscintigraphy, have been widely investigated during 20 last years. This technic appeared quite interesting, complementary of morphological imaging, and clinically useful, but difficult on a practical point of view because of several pharmacological and immunological limitations. For these reasons, despite several consequent improvements (especially two-steps or pre-targeting methods), immunoscintigraphy is currently not widely used; furthermore, other scintigraphic methods, mainly positron emission tomography with 18F-fluorodeoxyglucose, are efficient and easier to perform. On the other hand, knowledge of the biodistribution of radiolabeled antibodies allows the development of their therapeutic use, i.e. radioimmunotherapy, which represents a new method of cancer treatment. Radioimmunotherapy has several particular radiobiological and dosimetric aspects, which remain widely under investigation. Understanding of these aspects, together with a better delineation of the indications, allow to be really optimist concerning this new way of cancer treatment, as shown by clinical results that have been obtained in non Hodgkin's lymphoma. Radiolabeled immunoconjugates appears as a growing field in nuclear medicine, which sustains numerous preclinical and clinical studies.
Asunto(s)
Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Radioinmunodetección/métodos , Radioinmunoterapia/métodos , Anticuerpos Monoclonales/uso terapéutico , Predicción , Humanos , Inmunotoxinas/uso terapéutico , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/radioterapia , Radioisótopos/uso terapéutico , Radiofármacos/uso terapéuticoRESUMEN
Immunoscintigraphy using indium-111-labeled OC125 monoclonal antibody F(ab')2 fragments is a technic complementary of morphological imaging (i.e. ultrasonography and computed tomography). It allows early detection of recurrences of ovarian carcinomas. We performed immunoscintigraphy 30 times in 26 patients who previously underwent radical treatment for ovarian carcinoma, and were suspected to have a recurrence. Our purposes were appreciation of diagnostic accuracy of the method, and above all its impact on clinical decisions and evolution of the patients. There were, after reevaluation of the results, 18 true positives, 7 true negatives, 3 false negatives and 2 false positive cases (sensitivity 85.7%, specificity 77.8%). Bayesian analysis showed positive and negative predictive values of 86% and 87% when probability of recurrence a priori was 50%, and 80% and 58% when probability of recurrence a priori was 70%. The result of immunoscintigraphy contributed to clinical decisions in 24 cases out of 30, and led to a correct decision for the patient in 21 cases. Conversely, for the 6 cases in which the result has not been considered, to take this result into account would have been beneficial in 4 cases, but harmful in 2. Finally, survival tended to be longer when immunoscintigraphy was negative, which could be associated with a better prognosis. We conclude that OC125-immunoscintigraphy may be useful for ovarian carcinoma follow-up and may contribute to a better therapeutic strategy.
Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Anticuerpos Monoclonales/uso terapéutico , Antígeno Ca-125/inmunología , Neoplasias Ováricas/diagnóstico por imagen , Radioinmunodetección , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anticuerpos Monoclonales/inmunología , Femenino , Francia , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Tasa de SupervivenciaRESUMEN
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a scintigraphic imaging technique undergoing a rapid growth in the field of oncology. The constant progress of the detectors, either CDET or PET dedicated cameras, allows to obtain in routine conditions images with a 5 mm spatial resolution. Absolute tracer uptake quantification is also possible, which allows to evaluate objectively therapy efficacy. The mechanisms of FDG tissular accumulation are now better understood. Increase of glycolysis and of transmembrane transport of glucose seems to be at the origin of the high tumorous accumulation of FDG. The main current oncologic application of FDG PET is the diagnosis of malignancy of the isolated pulmonary nodules, with a sensitivity of more than 95%, and in the staging of lung cancer where PET shows higher performances than conventional imaging. The same stands in cutaneous melanoma and for malignancies of the digestive tract, either in colorectal, pancreatic or esophageal localizations. In colorectal cancers, the role of PET has for long being recognized in the differential diagnosis between recurrence and postoperative fibrosis. In the head and neck tumors, FDG also allows to differentiate between recurrence and postradiation necrosis. In lymphoma, the most suitable site for biopsy can be identified on a PET scan and therapy efficacy can also be assessed. In breast cancer, the detection of metastases seems to be possible with FDG. In brain and thyroid cancers, the role of FDG PET remains to be further determined. The low uptake of FDG in prostate cancer metastasis is not in favor of its use in this indication. In conclusion, the indications of FDG PET in oncology are now becoming more precise and it can be expected that clinical PET centers will soon appear in France.
Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias/diagnóstico por imagen , Radiofármacos , Tomografía Computarizada de Emisión , Neoplasias del Sistema Digestivo/diagnóstico por imagen , Femenino , Glucosa/metabolismo , Glucólisis , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Linfoma/diagnóstico por imagen , Masculino , Neoplasias/metabolismoRESUMEN
Venous thromboembolism (VTE) and pulmonary (PE) are difficult to diagnose. Pulmonary scintigraphy is a key investigation in the diagnosis of PE due to its innocuity and high sensitivity. A complete examination requires analysis of ventilation and perfusion (with at least four different views). The sensitivity of the method is excellent and a normal perfusion pulmonary scintigraphy excludes the diagnosis (10-15% of cases). On the other hand, the specificity is not nearly as good as only 10 to 15% of scintigraphies show changes which make the diagnosis of PE certain. In about 2 out of 3 cases, pulmonary scintigraphy alone is not decisional and only allows an estimation of the probability of PE this investigation must be integrated in the diagnostic strategy based on the "a priori" clinical probability, non invasive venous exploration and, in second intention, pulmonary angiography. The authors report the diagnostic strategy defined in Grenoble University hospital after multidisciplinary concertration. An evaluation in 103 patients with suspected PE showed a divergence from this diagnostic protocol in 38% of cases. However, when the protocol is respected, a therapeutic decision can be taken in 73% of cases based on clinical assessment scintigraphy and Doppler ultrasonography. Therefore, the diffusion and observance of these diagnostic strategies should be improved. In these conditions, pulmonary scintigraphy plays an essential role in the diagnosis of PE. The necessity of a control pulmonary scintigraphy and the value of systematic scintigraphy in the presence of proximal venous thrombosis are also discussed.
Asunto(s)
Embolia Pulmonar/diagnóstico por imagen , Adulto , Anciano , Árboles de Decisión , Femenino , Humanos , Pierna/irrigación sanguínea , Pierna/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Probabilidad , Embolia Pulmonar/fisiopatología , Cintigrafía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Trombosis/diagnóstico , Ultrasonografía , Venas , Relación Ventilacion-PerfusiónRESUMEN
Malaria remains one of the major public health problem in tropical and subtropical world. Malaria pathogeny depends partly on parasite multiplication and partly on some elements of the immunological response. It has recently become evident that one of these elements, Tumor Necrosis Factor (TNF), is directly implicated in the pathogenesis of cerebral malaria. TNF increase cytoadherence of infected erythrocytes to the brain microvascular endothelium. In a study involving african children with cerebral malaria high levels of TNF were positively correlated with a fatal outcome. We have previously demonstrated that in vitro Plasmodium falciparum products can directly stimulate the production of TNF from human macrophages. The aim of this work was to identify this soluble parasitic substance. Our results demonstrated that this substance could be a repetitive amino-acid sequence of the Ring-infected Erythrocyte Surface Antigen (RESA). The immunization against this kind of well-known peptides may be used as anti-disease vaccine. The elimination of mortality would be an essential target instead of parasitic clearance.