Clinical trial NCT05361083: First-in-human Evaluation of [18F]CETO
Official title: Studies of 18F-CETO as a Tracer for Adrenal PET Diagnostics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Primary Aldosteronism Due to Aldosterone Producing Adenoma
Primary Aldosteronism Due to Nodular Hyperplasia
Adrenal Cushing Syndrome
Non-Secretory Adrenal Adenoma
Adrenocortical Carcinoma
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
name: British Medical Research Council
First posted: 2022-05-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Purpose of this clinical phase 1 trial was to determine if para-chloro-2-\[18F\]fluoroethyletomidate positron emission computed tomography (\[18F\]CETO-positron emission computed tomography(PET)/computed tomography(CT)) can be used in diagnostics of adrenal tumors and if the biochemical/pharmacological states conditions in humans with various illnesses, compared to healthy humans, such as the radio tracer is suitable?

Detailed description: After receiving oral and written information about the study and its potential risks, all participants provided written informed consent. All participants underwent a screening visit 1-28 days before their \[18F\]CETO PET/CT. At the screening visit their medical history was obtained, including besides information of previous disease(s) and medication, also a clinical examination, WHO performance status, height, weight, pulse rate and blood pressure, blood chemistry and haematology.

Right before the PET/CT investigation a baseline assessment was performed including:

* A physical examination according to Modified Early Warning Score (MEWS)
* 12-lead electrocardiogram (ECG)
* Any concomitant medications was recorded
* Medical history - occurrence of any new symptoms and events since the screening visit
* Hematology (International Normalized Ratio (INR) in patients with antiocoagulant treatment).
* Pregnancy test in women.
* Assessment of injection site monitored by visual inspection (rash and phlebitis)

Participants received on average 0,76 mikrograms (range 0,1-1.37 mikrograms) of administered mass of CETO in conjunction to the PET/CT investigation.

Potential adverse events were monitored closely during, and after the administration of \[18F\]CETO, with access to emergency medicine resources.

Each participant remained for observation at least 3 hours after administration of \[18F\]CETO and the following assessments were performed:

* Blood withdrawn for additional post-scan chemical analysis.
* Assessment of injection site monitored by visual inspection (rash and phlebitis).
* MEWS

The ten first participants were evaluated for serious adverse events/adverse events (SAE/AEs) the day after (approximately 24 hours after) performing the \[18F\]CETO PET due to the short half-life of the radionuclide used, fluorine- 18 (T1/2= 109.5 min). Safety reporting was assessed by use of clinical Adverse Events and Common Toxicity Criteria (CTC), laboratory and non-laboratory toxicities.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with adrenal incidentalomas with an concurrent overproduction of aldosterone or cortisol or no concurrent hormone production, or patients diagnosed with adrenocortical carcinoma
* For healthy volunteers inclusion criteria included no known diseases, no ongoing medication and no known adrenal anomalies.

Exclusion Criteria for patients and healthy volunteers:

* pregnancy, age below 18, claustrophobia

Primary outcomes:
measure: Evaluate safety of up to two administrations of [18F]CETO in up to 15 patients in comparison with 5 healthy controls.
timeFrame: Up to 1 day after the [18F]CETO PET/CT for each patient
Secondary outcomes:
measure: Evaluate [18F]CETO as a PET- biomarker for the adrenals and to diagnose and visualize primary aldosteronism, cortisol producing adrenocortical adenoma and non-functioning adrenocortical adenoma in up to 15 patients
timeFrame: Up to 24 month
measure: Biodistribution of [18F]CETO
timeFrame: Up to 22 month
measure: Compare uptake of [18F]CETO in normal adrenal glands in patients comparing healthy controls and determine the test - retest variability of [18F]CETO.
timeFrame: Up to 24 month
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Uppsala University and Uppsala University Hospital
name: Per Hellman, Professor
role: STUDY_DIRECTOR
References:
citation: Silins I, Sundin A, Lubberink M, O'Sullivan L, Gurnell M, Aigbirhio F, Brown M, Wall A, Akerstrom T, Roslin S, Hellman P, Antoni G. First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours. Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):398-409. doi: 10.1007/s00259-022-05957-9. Epub 2022 Sep 8.