Use of [18F]FET PET-MRI to Improve Detection of Pituitary Adenomas in Cushing's Disease

NCT07108244 — Not applicable, Enrolling by invitation, 43 participants, University Hospital, Basel, Switzerland

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Use of [18F]FET PET-MRI to Improve Detection of Pituitary Adenomas in Cushing's Disease - a Prospective Diagnostic Study

Registry	NCT07108244, acronym FIND
Status	Enrolling by invitation
Phase	Not applicable
Study type	Interventional; na, single group, masking: none, diagnostic
Enrollment	43 (Estimated)
Sponsor	University Hospital, Basel, Switzerland (Other); collaborators: Erasmus Medical Center
Conditions	Cushing Disease
Interventions	[18F]FET PET-MRI (Diagnostic test)
Dates	start 2026-06-04, primary completion 2029-07-30 (estimated), completion 2029-07-30 (estimated), first posted 2025-08-06, last updated 2026-07-06
Locations	2 sites in Netherlands, Switzerland

-Summary

In ACTH-dependent hypercortisolism it is important to distinguish between Cushing's disease (CD), with ACTH production by a pituitary neuroendocrine tumour (PitNET) and Cushing's syndrome (CS), with ectopic ACTH production. Bilateral inferior petrosal sinus sampling (IPSS) is the gold standard for this distinction, with a diagnostic accuracy of 98%. However, IPSS is an invasive procedure and an indi-rect diagnostic method, rarely providing reliable data on the exact location of the PitNET. This has a major impact on the therapeutic approach, short and long-term remission rates, and other outcomes. Hybrid Positron-emission tomography-Magnetic Resonance Imaging (PET-MRI) using O-(2-\[18F\]-fluo-roethyl)-L-tyrosine (\[18F\]FET) is promising in this respect. Recent data published by our research group demonstrate a a sensitivity of 100% a high accuracy in in the precise localization of ACTH-secreting PitNETs. We hypothesize that \[18F\]FET PET-MRI could become the new non-invasive diagnostic stand-ard, but data regarding a direct comparison between the diagnostic impact of \[18F\]FET PET-MRI versus IPSS in the differentiation between CD and ectopic CS are lacking. In addition, there are currently no other reliable biomarkers to distinguish the two disorders. The investigators hypothesize that the ACTH-dependent biomarker copeptin could be a valuable addition in this regard. The aim of this prospective diagnostic study is to compare the diagnostic accuracy of \[18F\]FET-PET-MRI and IPSS in differentiating CD from ectopic CS in patients with ACTH-dependent hypercortisolism.

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+Arms and interventions

Arm	Type	Interventions	Description
[18F]FET-PET-MRI vs IPSS for diagnosing CD vs ectopic CS in ACTH-dependent cases	Other	Diagnostic Test: [18F]FET PET-MRI	Participants will undergo both \[18F\]FET-PET-MRI and inferior petrosal sinus sampling (IPSS) to evaluate their diagnostic performance in differentiating Cushing's disease from ectopic ACTH secretion. Results of both procedures will be made available to the treating medical team and participants as they become available.

[18F]FET PET-MRI (Diagnostic test): All participants will undergo both \[18F\]fluoroethyltyrosine positron emission tomography-magnetic resonance imaging (\[18F\]FET-PET-MRI) and inferior petrosal sinus sampling (IPSS) as part of the diagnostic work-up for ACTH-dependent hypercortisolism. The purpose is to compare the diagnostic accuracy of these two modalities in distinguishing Cushing's disease from ectopic ACTH secretion. The results from both diagnostic tests will be communicated to the treating medical team and the participant to guide further clinical management.

+Outcome measures

Primary outcomes

Comparison of the proportion of correct distinctions between CD and ectopic CS in patients with ACTH-dependent hypercortisolism using [18F]FET PET-MRI versus IPSS [Patients will receive standard surgical or radiotherapeutic treatment. The study will collect follow-up data 3-6 months post-treatment without influencing clinical management or requiring study-specific visits.]: The difference in the proportion of correct distinction between CD and ectopic CS in patients with ACTH-dependent hypercortisolism using \[18F\]FET PET-MRI versus IPSS

Secondary outcomes

Copeptin values during IPSS [During the IPSS]: Best fit of diagnostic copeptin values for differentiation between CD and ectopic CS with the inferior petrosal sinus sampling (IPSS) after desmopressin injection,
ACTH values during IPSS [During the IPSS]: Best fit of diagnostic ACTH values for differentiation between CD and ectopic CS with the inferior petrosal sinus sampling (IPSS) after desmopressin injection
Comparison of the diagnostic accuracy between [18F]FET PET-MRI and IPSS for differentiating between CD and ectopic CS in patients with ACTH-dependent hy-percortisolism [Follow-up data 3-6 months post-treatment]: ROC AUC of the \[18F\]FET PET-MRI and IPSS in differentiating CD from ectopic CS Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the \[18F\]FET PET-MRI and IPSS for differentiation between CD and ectopic CS
Exact localization of small functional PitNETs in patients with CD using the [18F]FET PET-MRI [perioperative]: Stated as left, central or right side, assessed by an experienced nuclear medicine physician and neuroradiologist Sensitivity, specificity, PPV and NPV of the \[18F\]FET PET-MRI for the exact localization of small functional PitNETs in patients with CD
Exact localization of small functional PitNETs in patients with CD using the inferior petrosal sinus sampling (IPSS) [perioperative]: Sensitivity, specificity, PPV and NPV of the IPSS for the exact localization of small functional PitNETs in patients with CD
Exact localization of small functional PitNETs in patients with CD using the structural MRI [perioperative]: Sensitivity, specificity, PPV and NPV of the structural MRI for the exact localization of small functional PitNETs in patients with CD

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥18 years
* Biochemically confirmed ACTH-dependent hypercortisolism, defined as:
* Non-suppressed ACTH levels plus minimal 2 of the following:
* Overnight 1mg dexamethasone suppression test > 50 nmol/L
* Elevated late night salivary cortisol (min. 2/3 measurements)
* Elevated 24-hours urinary free cortisol (min. 2 measurements)
* Pituitary microadenoma (< 10mm) OR negative / inconclusive findings on standard MRI of the pituitary sella-region.
* Indication for further evaluation with IPSS

Exclusion Criteria:

* Non-ACTH dependent hypercortisolism
* Pituitary macroadenoma (≥ 10mm)
* Suspicion of Pseudo-Cushing's disease (e.g. due to alcohol use disorder, PCO's, obesity, de-pression) according to standard work up / guidelines
* use of glucocorticosteroids
* Impaired renal function, defined as eGFR (MDRD) <30ml/min/1,73 m2. An exception can be made in consultation with the treating physician.
* Impaired Liver function
* Pregnancy/breastfeeding. For the latter, temporary discontinuation may be considered.
* Known allergic reaction to therapeutic radiopharmaceuticals.

+Locations (2)

Facility	City	Country	Status
Erasmus University Medical Centre	Rotterdam, South Holland	Netherlands
University Hospital Basel	Basel, Canton of Basel-City	Switzerland

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