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. 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.

Diagnostic accuracy of Bilateral Inferior Petrosal Sinus Sampling: The Experience of a Tertiary Centre

“…Alzahrani et al [24] obtained a sensitivity of 18 F-FDG-PET/CT of 58 % in locating ACTHsecreting adenomas and Feng et al [25] also found an unsatisfactory sensitivity of 53 %. The results with 11 C-Methionine-PET/CT seem to be promising, with a sensitivity of 100 % found by Feng et al [25] and Ikeda et al [26] (studies with 15 and 11 patients, respectively); nevertheless, these are still small series of patients and other authors like Koulouri et al found less positive results [27].…”

Clinical Evaluation of 11C-Met-Avid Pituitary Lesions Using a ZTE-Based AC Method

“…The identified pathologies included Cushing's disease (48%), thyrotropinsecreting pituitary adenoma (20%), acromegaly (12%), nonfunctioning pituitary adenoma (12%), prolactinoma (4%). Tumor volumes ranged from 195 mm 3 to 6702 mm 3 , with an average of 1452 mm 3 and median of 375 mm 3 .…”

“…A separate reconstruction was performed with each of the three attenuation maps (PETatl , PETZTE and PETCT). The reconstruction parameters were selected to mimic those of the PET/CT clinical protocol, while accounting for the limitations imposed by the different detector geometry: Fully 3D ordered subsets expectation maximization algorithm with time-offlight information (VPFX), iterations 9, subsets 8, matrix 128 × 128 × 89, voxel size 2.34 × 2.34 × 2.78 mm 3 , transaxial post-reconstruction Gaussian filter 4mm, axial filter 1:2:1, point-spread function, normalization, randoms, scatter, dead-time and decay corrections.…”

“…Recent work has shown 11 C-Methionine positron emission imaging (PET) to provide valuable complementary information: E.g. to identify residual adenoma in patients with persistent acromegaly after therapy [2] or to facilitate targeted surgical therapy of corticotropin-secreting tumors in Cushing's syndrome [3], as well as radiosurgery planning and radiotherapy [4].…”

Cryptococcal meningitis after transnasal transsphenoidal pituitary microsurgery of ACTH-secreting pituitary adenoma

“…Also, a group of Cambridge team testified that 11C-methionine positron emission tomography–computed tomography may play a role in detection and treatment of ACTH-secreting tumors in Cushing syndrome. [13] Apart from surgical reintervention of the ACTH-secreting adenomas, there are alternatives including radiotherapy, adrenal surgery, and pharmaceutical therapy. [14] Progression has been made in the field of drug development, and pasireotide, [15] mifepristone, ketoconazole, metyrapone, and cabergoline [16] have approved effective in managing Cushing disease.…”