Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone.

This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected (125)I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting (125)I-labeled PSA30. Tissue uptake of (125)I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, (18)F-fluoro-deoxy-glucose ((18)F-FDG) or (18)F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high (125)I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either (18)F-FDG or (18)F-choline. Biodistribution of (125)I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24-48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa

Validação do Modified Pulmonary Functional Status and Dyspnea Questionnaire e da escala do Medical Research Council para o uso em pacientes com doença pulmonar obstrutiva crônica no Brasil Validation of the Modified Pulmonary Functional Status and Dyspnea Questionnaire and the Medical Research Council scale for use in Brazilian patients with chronic obstructive pulmonary disease

OBJETIVO: Verificar a validade e a reprodutibilidade do uso de dois instrumentos subjetivos para avaliar a limitação nas atividades da vida diária (AVD) em pacientes com doença pulmonar obstrutiva crônica (DPOC) no Brasil: o Pulmonary Functional Status and Dyspnea Questionnaire - Modified version (PFSDQ-M) e a escala do Medical Research Council (MRC). MÉTODOS: Trinta pacientes com DPOC (17 homens; idade, 67 ± 10 anos; volume expiratório forçado no primeiro segundo, 42% ± 13% do predito) responderam por duas vezes às versões em português dos dois instrumentos com intervalo de uma semana. O PFSDQ-M contém três componentes: influência da dispnéia nas AVD, influência da fadiga nas AVD, e mudança nas AVD em comparação ao período anterior à doença. A escala do MRC é simples, com apenas cinco itens, dentre os quais o paciente escolhe qual o seu nível de limitação nas AVD devido à dispnéia. O tradicional questionário Saint George's Respiratory Questionnaire (SGRQ), já validado para o uso no Brasil, foi utilizado como critério de validação. RESULTADOS: A confiabilidade em reteste do PFSDQ-M utilizando o coeficiente de correlação intraclasse foi de 0,93, 0,92 e 0,90 para os componentes dispnéia, fadiga e mudança, respectivamente, enquanto que esta foi de 0,83 para a escala do MRC. A análise dos gráficos de Bland e Altman mostrou boa concordância entre a aplicação e a reaplicação do PFSDQ-M. Os componentes do PFSDQ-M e a escala do MRC se correlacionaram significativamente com os domínios e o escore total do SGRQ (0,49 < r < 0,80; p < 0,01 para todos). CONCLUSÕES: As versões em língua portuguesa do PFSDQ-M e da escala do MRC demonstraram ser reprodutíveis e válidas para o uso em pacientes com DPOC no Brasil.<br>OBJECTIVE: To determine the validity and reproducibility of two subjective instruments to assess limitations in activities of daily living (ADLs) in patients with chronic obstructive pulmonary disease (COPD) in Brazil: the Pulmonary Functional Status and Dyspnea Questionnaire - Modified version (PFSDQ-M) and the Medical Research Council (MRC) scale. METHODS: Thirty patients with COPD (age, 67 ± 10 years; males, 17; forced expiratory volume in one second, 42% ± 13% of predicted) completed the Portuguese-language versions of the two instruments on two occasions, one week apart. The PFSDQ-M has three components: influence of dyspnea on ADLs, influence of fatigue on ADLs change in ADLs experienced by the patient. The MRC scale is simple, with only five items, in which patients report the degree to which dyspnea limits their performance of ADLs. The traditional Saint George's Respiratory Questionnaire (SGRQ), previously validated for use in Brazil, was used as a validation criterion. RESULTS: The test-retest reliability (intraclass correlation coefficient) of the PFSDQ-M was 0.93, 0.92 and 0.90 for dyspnea, fatigue and change components, respectively, compared with 0.83 for the MRC scale. Bland-Altman plots showed good test-retest agreement for the PFSDQ-M. The components of the PFSDQ-M and the MRC scale correlated significantly with all of the domains and the total score of the SGRQ (0.49 < r < 0.80; p < 0.01 for all). CONCLUSIONS: The Portuguese-language versions of the PFSDQ-M and the MRC scale proved reproducible and valid for use in patients with COPD in Brazil