RESUMO
Antibody-based reagents represent a promising strategy as clinical diagnostic tools. Prostate cancer (PCa) is the second-leading cause of death in males in the Western population. There is a presently unmet need for accurate diagnostic tool to localize and define the extent of both primary PCa and occult recurrent disease. One of the most suitable targets for PCa is the prostate-specific membrane antigen (PSMA) recognised by the monoclonal antibody D2B that we re-shaped into the single chain Fv (scFv format). Aim of this study was to evaluate in preclinical in vivo models the target specificity of scFvD2B after labelling with different radionuclides. (111)In radiolabelling was performed via the chelator Bz-NOTA, and (131)I radioiodination was performed using iodogen. The potential for molecular imaging and the biological behaviour of the radiolabelled scFvD2B were evaluated in mice bearing two subcutaneous PCa isogenic cell lines that differed only in PSMA expression. Biodistribution studies were performed at 3, 9, 15 and 24h after injection to determine the optimal imaging time point. A significant kidney accumulation, as percentage of injected dose of tissue (%ID/g), was observed for (111)In-scFvD2B at 3h after injection (45%ID/g) and it was maintained up to 24h (26%ID/g). By contrast, kidney accumulation of (131)I-scFvD2B was only marginally (0.3%ID/g at 24h). At the optimal time point defined between 15h and 24h, regardless of the radionuclide used, the scFvD2B was able to localize significantly better in the PSMA expressing tumours compared to the negative control; with (131)I-scFvD2B yielding a significantly better target/background ratio compared to (111)In-scFvD2B. These data suggest that, besides antigen specificity, chemical modification may affect antibody fragment biodistribution.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Superfície/imunologia , Glutamato Carboxipeptidase II/imunologia , Compostos Radiofarmacêuticos/imunologia , Anticorpos de Cadeia Única/imunologia , Animais , Anticorpos Monoclonais/farmacocinética , Especificidade de Anticorpos/imunologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Radioisótopos de Índio/farmacocinética , Radioisótopos do Iodo/farmacocinética , Masculino , Camundongos Nus , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/farmacocinética , Anticorpos de Cadeia Única/farmacocinética , Fatores de Tempo , Distribuição Tecidual , Transplante HeterólogoRESUMO
AIM OF THE STUDY: Incidental/therapeutic thyroid irradiation causes hypothyroidism and nodular disease. Increasing numbers of children are being cured of cancers by treatments that include radiation also involving the thyroid bed: these children warrant an early diagnosis and treatment of any radiation-related thyroid changes. METHODS: In 1998 we retrospectively evaluated thyroid parenchyma/function in all patients irradiated between 1975 and 1997; thereafter, we prospectively evaluated all patients given thyroid irradiation by means of thyroid ultrasound and serum fT3, fT4, TSH and thyroglobulin. RESULTS: Of 596 eligible patients, 468 agreed to the retrospective evaluation: 128/468 had one or more thyroid nodules, and 73 of these 128 had concomitant or previously untreated hypothyroidism, while 22/128 had a differentiated carcinoma. Another 144/157 patients treated between 1998 and 2004 were evaluated and any iatrogenic hypothyroidism was promptly treated: 19/144 had nodules, all smaller than 1cm in diameter. The first patient group was studied retrospectively, so we have no precise record of the time of nodule occurrence or of their initial sizes. We found, however, that both the number of patients with nodules and the sizes of the nodules were significantly lower (p<0.01) in the prospectively studied group (after a median follow-up of 81 months) than in the retrospectively studied group. Among all the patients with nodules, significantly more females developed cancer than males (p<0.04). CONCLUSIONS: Early treatment for hypothyroidism and ultrasound evaluation of the parenchyma are needed to limit nodule onset and growth.
Assuntos
Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/etiologia , Nódulo da Glândula Tireoide/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hipotireoidismo/etiologia , Lactente , Masculino , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Segunda Neoplasia Primária/metabolismo , Estudos Prospectivos , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Testes de Função Tireóidea , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Encouraging results have been recently reported in selected patients affected by pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The selection factors predicting clinical outcome are still a matter of clinical investigation. We assessed the prognostic reliability of serum tumor markers in a large series of patients with PMP undergoing CRS and HIPEC. METHODS: Sixty-two patients with PMP were operated on at a single institution with the intent of performing adequate CRS (residual tumor nodules