RESUMO
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.
Assuntos
Imunoterapia , Melanoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor de Morte Celular Programada 1/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Fluordesoxiglucose F18 , Humanos , Imunoterapia/métodos , Imunoterapia/mortalidade , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Carga TumoralRESUMO
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.
Assuntos
Integrina alfaVbeta3/metabolismo , Lutécio/uso terapêutico , Peptídeos Cíclicos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Integrina alfaVbeta3/genética , Lutécio/efeitos adversos , Lutécio/farmacocinética , Camundongos , Camundongos Nus , Neoplasias Experimentais/genética , Neoplasias Experimentais/radioterapia , Peptídeos Cíclicos/efeitos adversos , Peptídeos Cíclicos/farmacocinética , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/farmacocinéticaRESUMO
We recently treated one patient presenting with a disseminated non-operable Merkel cell carcinoma (MCC) by lanreotide (somatostatin analog), with a complete remission of the disease and a follow up of 17 months. We present in this paper a case report with a review of the utilization of somatostatin analogues in the treatment of MCC.
Assuntos
Carcinoma de Célula de Merkel/tratamento farmacológico , Indução de Remissão , Neoplasias Cutâneas/tratamento farmacológico , Somatostatina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Cutâneas/cirurgia , Somatostatina/uso terapêuticoRESUMO
PURPOSE: Neoplastic meningitis is often the final outcome of disseminated cancer and is rapidly lethal. Its limited treatment relies on systemic or intrathecal chemotherapy with methotrexate (MTX) or thiotepa. When 5-iodo-2'-deoxyuridine labeled with (125)I ((125)IUdR) is incorporated into the DNA of mitotic tumor cells, the Auger electrons emitted during iodine decay are highly cytotoxic. The radiotherapeutic efficacy of (125)IUdR administered intrathecally has also been established in animals bearing spinal cord tumors, and MTX is known to potentiate the response. This approach has not been tested in the clinic. METHODS: A 44-year-old woman, with locally advanced pancreatic cancer, was treated for three years with complete systemic remission, but then relapsed with cytologically proven neoplastic meningitis. The patient was given four successive intrathecal injections of MTX (10 mg) every 12 h and, with the fourth dose, 1850 MBq (125)IUdR, followed by four additional MTX doses. The response was monitored by cytology and CA19.9 (carbohydrate antigen 19.9) levels in the cerebrospinal fluid (CSF) as well as by clinical status of the patient. RESULTS: The follow-up of cytology and CA19.9 levels in the CSF showed dramatic improvement within 26 days followed by a biological relapse on Day +36. There was no evidence of local central nervous system toxicity. Three months later, neoplastic meningitis recurred and meningeal tumor infiltration was observed on magnetic resonance imaging. Six months after MTX-(125)IUdR treatment, the patient died. CONCLUSION: (125)IUdR treatment proved to be feasible without acute neurological toxicity and seemed to have produced a biological response. This attempt provides the basis for designing prospective clinical trials.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Idoxuridina/uso terapêutico , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/radioterapia , Metotrexato/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Adulto , Antibióticos Antineoplásicos/administração & dosagem , Antígenos Glicosídicos Associados a Tumores/líquido cefalorraquidiano , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Evolução Fatal , Feminino , Humanos , Idoxuridina/administração & dosagem , Injeções Espinhais , Radioisótopos do Iodo , Neoplasias Meníngeas/secundário , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Compostos Radiofarmacêuticos/administração & dosagemRESUMO
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.
Assuntos
Medula Óssea/patologia , Osso e Ossos/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radioimunoterapia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/radioterapiaAssuntos
Oncologia/métodos , Medicina Nuclear/métodos , Tomografia Computadorizada de Emissão/métodos , Carcinoma Hepatocelular/radioterapia , Contraindicações , Meios de Contraste/uso terapêutico , Fluordesoxiglucose F18 , Humanos , Radioisótopos do Iodo/uso terapêutico , Óleo Iodado/uso terapêutico , Neoplasias Hepáticas/radioterapia , Metástase Linfática/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Radioimunoterapia/métodos , Compostos RadiofarmacêuticosRESUMO
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.
Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Radioimunodetecção/métodos , Radioimunoterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Previsões , Humanos , Imunotoxinas/uso terapêutico , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
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.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Carcinoma Medular/radioterapia , Haptenos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Radioimunoterapia , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Idoso , Anticorpos Anti-Idiotípicos/sangue , Anticorpos Biespecíficos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoterapia/efeitos adversos , Dosagem RadioterapêuticaRESUMO
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.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígeno Carcinoembrionário/imunologia , Carcinoma de Células Pequenas/radioterapia , Haptenos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/radioterapia , Ácido Pentético/imunologia , Radioimunoterapia , Idoso , Animais , Anticorpos Anti-Idiotípicos/sangue , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Dosagem RadioterapêuticaRESUMO
Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Neoplasias Ósseas/diagnóstico , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Queratina-19 , Queratinas , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Cintilografia , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99mRESUMO
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.
Assuntos
Neoplasias/radioterapia , Radioimunoterapia/métodos , Animais , Anticorpos Biespecíficos/farmacocinética , Anticorpos Biespecíficos/uso terapêutico , Carcinoma Medular/diagnóstico por imagem , Carcinoma Medular/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Neoplasias/diagnóstico por imagem , Radioimunodetecção , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
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".
Assuntos
Neoplasias/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Radioisótopos/química , Humanos , Oligonucleotídeos Antissenso/químicaRESUMO
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.
Assuntos
Anticorpos Biespecíficos , Carcinoma Medular/diagnóstico por imagem , Haptenos , Radioisótopos de Índio , Radioimunodetecção/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto , Idoso , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/imunologia , Carcinoma Medular/secundário , Carcinoma Medular/cirurgia , Feminino , Humanos , Cuidados Intraoperatórios , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Ácido Pentético , Cintilografia/instrumentação , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
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.
Assuntos
Fluordesoxiglucose F18 , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Neoplasias do Sistema Digestório/diagnóstico por imagem , Feminino , Glucose/metabolismo , Glicólise , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Masculino , Neoplasias/metabolismoRESUMO
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.
Assuntos
Anticorpos Biespecíficos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Haptenos , Radioisótopos de Índio , Neoplasias Pulmonares/diagnóstico por imagem , Ácido Pentético , Radioimunodetecção/métodos , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Mediastino/diagnóstico por imagem , Estadiamento de Neoplasias , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Anticorpos Monoclonais/uso terapêutico , Antígeno Ca-125/imunologia , Neoplasias Ovarianas/diagnóstico por imagem , Radioimunodetecção , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Feminino , França , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Taxa de SobrevidaRESUMO
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.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Queratinas/sangue , Neoplasias Pulmonares/sangue , Serpinas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Queratina-19 , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
In vivo immunotargeting of specific antigens with radiolabeled monoclonal antibodies is a new method of diagnosis which has largely improved over the past 15 years. It has been especially developed in the oncologic field. Although it is not yet a daily procedure, immunoscintigraphy has been proven a useful diagnostic tool in many situations. It gives information about the presence of lesions and their neoplastic nature. For this reason, immunoscintigraphy appears as very complementary to morphological imaging and is mainly indicated when lesions have insufficient anatomical definition. Early detection of recurrences is actually the best indication of immunoscintigraphy. However, some problems still exist, concerning the tumor/tissues uptake ratio which is not sufficient for an optimal imaging contrast, and the apparition of human anti-mouse antibodies (HAMA) in the patients. At present, many works are in progress which could resolve these problems. Ultimately, well-performed clinical trials are necessary to establish the right place for immunoscintigraphy in the diagnostic and therapeutic strategies in oncology.