Optimisation of molecular imaging using 11C-methionine PET in the detection of pituitary adenomas

Abstract

Decision-making in pituitary disease is critically dependent on high-quality imaging of the sella and parasellar region. Magnetic resonance imaging (MRI) is the investigation of choice, and for the majority of patients combined T1 and T2 weighted sequences provide the information required to allow surgery, radiotherapy (RT) and/or medical therapy to be planned and long-term outcomes to be monitored. However, in some cases standard MRI sequences are indeterminate and additional information is needed to help inform the choice of therapy for a pituitary adenoma (PA). Pituitary molecular imaging using 11C-methionine positron emission tomography (11C-met-PET) is well described. This thesis adds to the existing literature reporting potential roles for molecular imaging in patients with different subtypes of PA. Specifically, it describes a series of novel approaches to pituitary imaging using 11C-met-PET with particular focus on optimisation to facilitate detection of occult PAs, and thereby allow definitive treatment to be recommended for a subset of patients who would otherwise be deemed unsuitable for surgery and/or RT. The first chapter provides an overview of pituitary adenomas and the modalities used in pituitary imaging, with emphasis on molecular imaging approaches described to date. In the second chapter, methods commonly applied during the conduct of the different research studies are described and, when required, these are further considered in each subsequent chapter. Chapter three reports findings from two retrospective cohort studies examining the potential roles of of 11C-met-PET in patients harbouring prolactin-secreting PAs, and in patients with residual acromegaly due to parasellar disease extension. In chapters four and five, two prospective studies describe novel approaches to image optimisation using biochemical suppression of 11C-met-PET signal in normal, and in adenomatous pituitary tissue, respectively. In the chapter six, results from a prospective study involving 15 patients with different types of PAs undergoing hybrid 11C-met-PET/MR are reported. The final chapter (seven) draws the various study findings together and considers how these can inform the design of future research projects and adoption by the NHS.