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

Study Overview
=================
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for observation at least 3 hours after administration of [18F]CETO and the following assessments were performed: Blood withdrawn for additional post-scan chemical analysis.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.

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

Conditions
-----------------
Primary Aldosteronism Due to Aldosterone Producing Adenoma, Primary Aldosteronism Due to Nodular Hyperplasia, Adrenal Cushing Syndrome, Non-Secretory Adrenal Adenoma, Adrenocortical Carcinoma

Intervention / Treatment
-----------------
* Drug: F18CETO


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: First-in-man investigastion of [18F]CETO<br>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<br>* Injection of F18CETO or O15water followed by PET/CT<br>* 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 |