First-in-human Evaluation of [18F]CETO

Studies of 18F-CETO as a Tracer for Adrenal PET Diagnostics

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?

Study Overview

• Status: Completed
• Conditions: Adrenocortical Carcinoma; Adrenal Cushing Syndrome; Primary Aldosteronism Due to Aldosterone Producing Adenoma; Primary Aldosteronism Due to Nodular Hyperplasia; Non-Secretory Adrenal Adenoma
• Intervention / Treatment: Drug: F18CETO

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• Blood withdrawn for additional post-scan chemical analysis.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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: First-in-man investigastion of [18F]CETO; 15 patients were investigated with PET/CT after injection of 2,5 MBq/kg [18F]CETO. 5 healthy volunteers were investigated twice (Test-retest), with approximately 2 weeks in-between each PET/CT investigation, after injection of 1,3 MBq/kg [18F]CETO. Arterial blood samples were taken as well as urinary sampels. 3 out of 5 healthy volunteers were also investigated twice with PET/CT after injection of 13,2 MBq/kg [15O]water, performed before the [18F]CETO PET/CT.

Drug: F18CETO; Injection of F18CETO or O15water followed by PET/CT; Other Names: Para-chloro-2-[18F]fluoroethyletomidate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate safety of up to two administrations of [18F]CETO in up to 15 patients in comparison with 5 healthy controls.	Number of patients with treatment-related adverse events as assessed by clinical Adverse Events and Common ToxicityNCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE)	Up to 1 day after the [18F]CETO PET/CT for each patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Arterial blood was collected to determined the fraction of intact [18F]CETO in plasma. PET- modelling based on dynamic PET-data and metabolite analysis was performed for scientific purposes. Measurement of Standard Uptake Value (SUV) was determined for the adrenal glands.	Up to 24 month
Biodistribution of [18F]CETO	Measurement of SUV for organs was determined.	Up to 22 month
Compare uptake of [18F]CETO in normal adrenal glands in patients comparing healthy controls and determine the test - retest variability of [18F]CETO.	Difference in SUV in the adrenal glands between two investigations in the samt participant was determined.	Up to 24 month

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: British Medical Research Council; Uppsala University Hospital
• Investigators: Study Director: Per Hellman, Professor, Uppsala University and Uppsala University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adenoma; Hyperplasia; Hyperaldosteronism; Cushing Syndrome; Adrenocortical Carcinoma
• Other Study ID Numbers: 2018-004831-64

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No