title: A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.
abstract: 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.
  
  
  METHODS
  Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) 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.
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Olympia
authors.initials: O
authors.lastname: Koulouri
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Steuwe
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gillett
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hoole
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Powlson
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Donnelly
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Burnet
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Nagui M
authors.initials: NM
authors.lastname: Antoun
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Heok
authors.initials: H
authors.lastname: Cheow
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Mannion
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.affiliation: Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science Departments of Nuclear Medicine Medical Physics Otolaryngology Oncology Neuroradiology Neurosurgery National Institute for Health Research, Cambridge Biomedical Research Centre, University of Cambridge & Addenbrooke's Hospital, Box 289, Hills Road, Cambridge CB2 0QQ, UK mg299@medschl.cam.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Gurnell
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging*; D049913:ACTH-Secreting Pituitary Adenoma / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging*; D000236:Adenoma / Q000150:complications / Q000175:diagnosis / Q000000981:diagnostic imaging*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002250:Carbon Radioisotopes; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000209:etiology; D049268:Positron-Emission Tomography; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D008715:Methionine