CETO
Research type
Research Study
Full title
A Phase I clinical trial evaluating the safety and efficacy of up to two administrations of the adrenal PET tracer [18F]CETO in healthy volunteers and patients with primary aldosteronism
IRAS ID
248713
Contact name
Mark Gurnell
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eudract number
2018-004851-18
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 5 months, days
Research summary
Research Summary
At least one quarter of the UK adult population has hypertension, a major risk factor for heart attacks and stroke. Primary aldosteronism (PA), a treatable form of hypertension, accounts for 5-10% of all cases, and 20-25% of difficult to control hypertension. Determining whether one (potentially curable with surgery) or both (requiring long-term drug treatment) adrenal glands are the source of PA in a patient remains challenging. Existing lateralising procedures (i.e. investigations to distinguish one from two gland involvement e.g. computed tomography or magnetic resonance imaging), have significant limitations. Accordingly, most patients must undergo an invasive procedure called adrenal vein sampling (AVS) in which small catheters are placed in each adrenal vein. However, this is time-consuming, technically demanding, and fails in 20-50% of cases.To address this, we have adopted a novel approach using PET-CT as an alternative to AVS. Currently, this uses a tracer called metomidate labelled with carbon-11 (11C MTO), which is taken up preferentially by the adrenal gland, and in particular by adrenal tumours causing PA. However, its utility is limited by a short half-life, which means the scan can only be performed in centres with a cyclotron facility (currently <10 NHS sites). We plan to investigate the safety of a new tracer with a longer half-life, [18F]CETO, that could be made available for use in many more centres. This is the first time the tracer will be administered in humans, and the study will take place at Cambridge University Hospitals NHS Foundation Trust. We will recruit up to five healthy volunteers and six patients with PA (three patients with single adrenal gland involvement and three where both adrenals are affected). The study is expected to last up to 4 months, and healthy volunteers will have a single [18F]CETO PET-CT scan, while patients will undergo two [18F]CETO scans.
Summary of Results
Primary aldosteronism (PA) is now recognised to be the most common, potentially curable cause of secondary hypertension. In approximately half of all cases, PA is caused by an abnormality in one adrenal gland. We have previously shown that the molecular PET tracer 11C-metomidate (MTO) allows localisation of the cause of PA in many of these patients and can facilitate potentially curative surgery. However, MTO is a radioactive tracer, which is active for only a short time. This limits its availability, and all UK patients must travel to Cambridge for a scan. We have therefore developed a related tracer, 18F-CETO (CETO), which is active for a longer time, and which could therefore be made available for use in other centres.
This First-in-Human study was designed to evaluate the safety of CETO and to confirm that it is taken up by human adrenal tissue. The study recruited 11 participants (five healthy volunteers and six patients with primary aldosteronism: three due to bilateral adrenal disease (i.e., affecting both adrenal glands) and three due to unilateral adrenal disease (i.e., affecting only one adrenal gland).
The study opened in March 2020 just prior to the COVID pandemic and the national lockdown that commenced at the end of the month. Accordingly, recruitment to the trial was immediately suspended and the trial opened again to recruitment in August 2020, with the first patient recruited on 11th August 2020. Recruitment was completed in November 2020.Evaluation of the safety of up to two administrations of [18F]CETO There were no serious adverse events, serious adverse reactions or suspected unexpected serious adverse reactions in the trial. A single adverse event (transient nausea) related to the administration of a medication called synacthen (to assess adrenal function) was observed, but consistent with the known potential side effect profile of this drug. Vital signs (blood pressure, pulse rate, pulse oximetry) were unchanged following CETO administration. ECGs demonstrated no clinically significant changes following CETO administration. Similarly, laboratory blood tests (full blood count, liver function tests, urea & electrolytes) taken before and the morning following CETO administration showed no changes. The trial also specifically examined cortisol reserve following CETO administration because of the theoretical possibility that the normal function of the adrenal glands might be temporarily reduced. However, no change in adrenal status was observed in any of the participants, thereby excluding even a short-lived reduction in adrenal function.
Assessment of [18F]CETO radiotracer uptake by the adrenal glands Measurements of CETO uptake were undertaken by two independent nuclear medicine physicians in a fully blinded manner. Clear CETO uptake was demonstrated in both adrenal glands in all participants. Comparatively, low uptake was observed in the liver in all participants.
Evaluation of uptake in bilateral vs unilateral cases of PA following CETO administration in six patients The abnormal adrenal glands in patients with both types of PA demonstrated higher uptake when compared to healthy volunteers and background normal adrenal tissue.
The trial objectives were therefore successfully met, and the investigators are now undertaking a follow up study (MATCH trial extension, Clinical Trials.gov identifier: NCT02945904). This is comparing CETO with the existing tracer metomidate (MTO) in patients with primary aldosteronism to ascertain whether CETO offers comparable accuracy in distinguishing both types of adrenal disease and can therefore replace MTO as the primary tracer in routine clinical use.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
19/LO/1814
Date of REC Opinion
7 Feb 2020
REC opinion
Further Information Favourable Opinion