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Objective: We report our experience of functional imaging with 11 C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Design: Twenty patients with i) de novo Cushing's disease (CD, nZ10), ii) residual or recurrent hypercortisolism following first pituitary surgery (Gradiotherapy; nZ8) or iii) ectopic Cushing's syndrome (nZ2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. Methods: All patients underwent 11 C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of 11 C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. Results: In seven of ten patients with de novo CD, asymmetric 11 C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal 11 C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, 11 C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. Conclusions:11 C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.

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