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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. [ABSTRACT FROM AUTHOR]

Abstract: Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the α4β2 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 200MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DVS). 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. [Copyright &y& Elsevier]

Positron emission tomography (PET) and the ligand [18F]fluoromisonidazole (18F-FMISO) have been used to image hypoxic tissue in the brain following acute stroke. Existing region of interest (ROI)-based methods of analysis are time consuming and operator-dependent. We describe and validate a method of statistical parametric mapping to identify regions of increased 18F-FMISO uptake. The 18F-FMISO PET images were transformed into a standardized coordinate space and intensity normalized. Then t statistic maps were created using a pooled estimate of variance. Statistical inference was based on the theory of Gaussian Random Fields. We examined the homogeneity of variance in normal subjects and the influence of normalization by mean whole brain activity versus mean activity in the contralateral hemisphere. Validity of the distributional assumptions inherent in parametric analysis was tested by comparison with a non-parametric method. The results of parametric analysis were also compared with those obtained with the existing ROI-based method. Variance in uptake at each voxel in normal subjects was homogeneous and not affected by mean voxel activity or distance from the centre of the image. The method of normalization influenced results significantly. Normalization by whole brain mean activity resulted in a smaller volume of tissue being classified as hypoxic compared to normalisation by mean activity in the contralateral hemisphere. The ROI-based method was subject to interobserver variability with a coefficient of variability of 16%. The volumes of hypoxic tissue identified by parametric and nonparametric methods were highly correlated (r = 0.99). These findings suggest that using a pooled variance and contralateral hemisphere normalisation, statistical parametric mapping can be used to objectively identify regions of increased 18F-FMISO uptake following acute stroke in individual subjects. [Copyright &y& Elsevier]