RESUMO
PURPOSE: Hypoxia is associated with aggressive tumour behaviour and can influence response to systemic therapy and radiotherapy. The prevalence of hypoxia in metastatic colorectal cancer is poorly understood, and the relationship of hypoxia to patient outcomes has not been clearly established. The aims of the study were to evaluate hypoxia in metastatic colorectal cancer with [18F]Fluoromisonidazole ([18F]FMISO PET) and correlate these findings with glycolytic metabolism ([18F]FDG PET) and angiogenic blood biomarkers and patient outcomes. METHODS: Patients with metastatic colorectal cancer received routine staging investigations and both [18F] FMISO PET and [18F] FDG PET scans. Correlative blood specimens were also obtained at the time of the [18F] FMISO PET scan. Patient follow-up was performed to establish progression-free survival. RESULTS: A total of 40 patients were recruited into the trial. [18F]FMISO and [18F]FDG PET scans showed a significant correlation of SUVmax (p = 0.003). A significant correlation of progression-free survival and [18F] FMISO TNR (p = 0.02) and overall survival with [18F]FMISO TNR (p = 0.003) and [18F]FDG TGV (p = 0.02) was observed. Serum levels of osteopontin, but not VEGF, correlated with [18F] FMISO and [18F]FDG PET scan parameters. CONCLUSION: [18F]FMISO PET uptake in metastatic colorectal cancer significantly correlates with glycolytic metabolism and is predictive of progression-free and overall survival. These findings have implications for the assessment and treatment of metastatic colorectal cancer patients with novel therapies which affect tumour angiogenesis and hypoxia.
Assuntos
Neoplasias Colorretais , Neoplasias de Cabeça e Pescoço , Biomarcadores , Neoplasias Colorretais/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Hipóxia/diagnóstico por imagem , Misonidazol , Tomografia por Emissão de Pósitrons , Prevalência , Compostos RadiofarmacêuticosRESUMO
Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease (AD). This study aimed to; (1) quantify nAChR distribution in vivo with 2-[18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched, healthy controls (HC) and (2) correlate nAChR distribution with cognitive performance in both groups. All participants were non-smokers and underwent cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DV(S)). The AD group differed significantly from HC on all cognitive measures employed, with impairments on measures of attention, working memory, language, executive function, visuospatial ability, verbal learning and verbal memory (p<.05). Contrary to post-mortem data this study found no evidence of in vivo nAChR loss in early AD despite significant cognitive impairment. Furthermore, no correlation between nAChR and cognitive performance was found for either group. The findings of the current study suggest preservation of nAChRs early in AD supporting previous studies. It is possible that while the clinical 2-FA PET method described here may be insensitive in detecting changes in early AD, such changes may be detected in more advanced stages of the illness.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Receptores Nicotínicos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/classificação , Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Comportamento de Escolha/fisiologia , Aprendizagem por Discriminação/fisiologia , Feminino , Radioisótopos de Flúor , Humanos , Inibição Psicológica , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Orientação/fisiologia , Resolução de Problemas/fisiologia , Desempenho Psicomotor/fisiologia , Piridinas , Tempo de Reação/fisiologia , Aprendizagem Verbal/fisiologiaRESUMO
PURPOSE: To assess the contribution of concurrent low-dose, noncontrast CT in the assessment of the malignant potential of incidental focal 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-avid colonic lesions on positron emission tomography/computed tomography (PET/CT). PROCEDURES: Routine FDG-PET/CT scans were reviewed for identification of focal FDG-avid colon lesions, and the CT component was independently reviewed for an anatomical lesion and malignant potential based on CT criteria. Clinical, endoscopic, and histopathology follow-up was obtained. RESULTS: A total of 85/2,916 (3%) oncology FDG-PET/CT scans had incidental focal colon lesions. Clinical and/or endoscopic follow-up was available in 83/85 (98%) patients. Focal, corresponding CT lesions were found in 44/83 (53%) patients, but features of malignancy were not assessable. Of the 44 patients with a final diagnosis, 32/44 (73%) were FDG-PET/CT true positives; 5/44 (11%) were false positives; and 7/44 (16%) had inconclusive FDG-PET/CT findings. CONCLUSIONS: Concurrent low-dose, noncontrast CT improves localization, but does not provide independent information on the malignant potential of incidental focal colonic activity on FDG-PET/CT.
Assuntos
Doenças do Colo/diagnóstico , Meios de Contraste/metabolismo , Fluordesoxiglucose F18 , Achados Incidentais , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Endoscopia , Reações Falso-Positivas , Seguimentos , HumanosRESUMO
BACKGROUND: Accurate staging of lung cancer is essential in determining the most appropriate management plan, as detection of occult metastasis can significantly alter management. AIMS: The aims of this study are to determine the prevalence of occult metastasis in patients undergoing 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) for evaluation of suspected/proven lung carcinoma and correlate pre-PET TNM stage with prevalence of metastasis. METHODS: FDG-PET, which identified patients with metastasis on institutional database, was re-evaluated by a nuclear medicine physician blinded to clinical information. The confidence level of metastasis was scored on a 5-point scale, with a score of >/=4 considered positive. RESULTS: There were 67 of 645 (10%) patients identified with suspected occult metastasis on FDG-PET. Twelve patients scoring =3 were excluded. Prevalence of occult metastasis was 10/156 (6%) in solitary pulmonary nodules (SPN); 22/319 (7%) and 23/170 (14%) in proven and suspected lung cancer, respectively. Positive predictive value of FDG-PET for metastasis was 8/10 (80%) in solitary pulmonary nodules, 14/20 (70%) and 17/21 (81%) in proven and suspected lung cancer, respectively. (18)F-FDG-avid lesions classified as false positives were patients with cholelithiasis, rib fractures and those with equivocal/negative bone scans or computed tomography on follow up. There was a higher incidence of true positive occult metastasis in patients in all stages of disease, particularly stage III disease. CONCLUSION: (18)F-FDG PET is predictive for occult metastatic disease in patients with solitary pulmonary nodules and proven or suspected lung cancer and is more likely to be present in all stages, particularly in stage III. PET findings should be actively pursued with correlative investigation to identify benign pathology in patients who remain candidates for curative treatment.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Metástase Neoplásica/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prevalência , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Nódulo Pulmonar Solitário/patologiaRESUMO
UNLABELLED: Radiolabeling monoclonal antibodies (mAbs) allows the evaluation of biodistribution of constructs in vivo through gamma camera imaging and also permits quantitation of mAb uptake in tumors through biopsy-based counting techniques. The quantitation of radiolabeled mAb uptake in cancer patients is complicated by the attenuation of gamma emissions of routinely used isotopes (e.g., 131I and 111In) and the spatial resolution and sensitivity of gamma cameras. METHODS: We used the positron-emitting isotope 124I (half-life [T1/2] = 4.2 d) to label the recombinant humanized anti-colorectal cancer A33 antibody (huA33) and evaluated its biodistribution properties and PET imaging characteristics in BALB/c nude mice bearing SW1222 colorectal xenografts and control colon tumors. RESULTS: The immunoreactivity of radioconjugate was 78% as determined using the cell-binding Lindmo assay. The apparent association constant was found to be 2.2 x 10(9) M(-1), and the number of antibody binding sites per cell was 371,000. The radioconjugate was found to be stable in serum obtained from mice at various times after injection. Assuming a two-compartment model with a four-parameter fit of mean blood levels, the T1/2alpha was 1.5 h and the T1/2beta was 38.2 h. Excellent tumor uptake was obtained, with maximal uptake reaching 50.0 +/- 7.0 percentage injected dose per gram of tumor by 4 d after injection. Specificity of localization was shown by lack of uptake in control tumor. PET imaging detected antigen-positive tumor by 4 h after injection, and high-resolution images were obtained by 24 h after injection. CONCLUSION: In clinical trials using PET, huA33 labeled with 124I has potential for imaging and staging colon tumors and quantifying antibody uptake in colon tumors in vivo.