RESUMO
In the framework of the preclinical validation of the hypoxic tracer [(18)F]EF3, a comparison was performed between uptake of [(18)F]EF3 and EF5 adducts detected by immunofluorescence in MCa-4, FSA, FSAII, Sa-NH and NFSA tumour-bearing mice. Mice were allowed to breath carbogen (5% CO(2), 95% O(2)), 21% oxygen or 10% oxygen. A significant correlation (r (2)=0.57; p<0.01) was found between the [(18)F]EF3 tumour-to-muscle ratio and the fluorescence intensity of EF5.
Assuntos
Etanidazol/análogos & derivados , Fibrossarcoma/diagnóstico por imagem , Fibrossarcoma/metabolismo , Hidrocarbonetos Fluorados/metabolismo , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/metabolismo , Nitroimidazóis/farmacocinética , Oxigênio/metabolismo , Animais , Hipóxia Celular , Avaliação Pré-Clínica de Medicamentos , Etanidazol/metabolismo , Imunofluorescência , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos C3H , Especificidade de Órgãos , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
The 2-nitroimidazole derivative 2-(2-nitroimidazol-1-yl)- N-(3,3,3-trifluoropropyl)acetamide (EF3) is a marker which forms adducts into hypoxic cells. Radiosynthesis of [(18)F]EF3 was recently performed by our group. Our aim was to study the pharmacokinetics, biodistribution, metabolism and specificity for hypoxia of [(18)F]EF3. MCa-4, SCC VII, NFSA, FSA, FSA II or Sa-NH tumour-bearing C3H mice were injected intravenously with [(18)F]EF3 and allowed to breathe air, 10% O(2) or carbogen until sacrifice 5-770 min after injection. Radioactivity was measured ex vivo in various organs, including urine and faeces. Selected organs were additionally processed to measure tracer metabolites with high-performance liquid chromatography. The half-life in blood was 73.9 min. [(18)F]EF3 was eliminated mainly via the kidneys, with 75% of the injected activity found in the urine by 12 h 50 min. The biodistribution was fast and homogeneous except in the brain and the bone, where it was significantly lower, and in the liver and the kidney, where it was significantly higher. In most organs, the exceptions being the gastrointestinal and urinary tract, tissue-to-blood ratios were below or close to unity. In tumours, a relative accumulation of the tracer was observed with time, which, at 220 min after injection, depended on tumour strain and oxygenation conditions, i.e. 10% O(2) significantly increased the tumour-to-muscle ratio whereas carbogen decreased it. [(18)F]EF3 was rapidly metabolised in the kidney and the liver. [(18)F]EF3 is a promising tracer for detection of tumour hypoxia. A phase I study in head and neck cancer patients is in progress at our institution.
Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/metabolismo , Fibrossarcoma/diagnóstico por imagem , Fibrossarcoma/metabolismo , Nitroimidazóis/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos C3H , Especificidade de Órgãos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
The management of lesions of the oral mucosa requires precise knowledges and expertise in clinical care. This review article summarise the principles of the most validated therapeutical features about lesions of the oral mucosa. Global management procedures are described. Therapeutic modalities involving drugs, surgery, radiotherapy, chemotherapy, immunotherapy, electrotherapy, gene therapy and photodynamic therapy are detailed as well.