First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours

Abstract

Purpose: [11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.

Methods: Fifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.

Results: Uptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65-70, and SUV120 were 25, 22, and 17%.

Conclusions: High adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki.

Trial registration: ClinicalTrials.gov , NCT05361083 Retrospectively registered 29 April 2022. at, https://ichgcp.net/clinical-trials-registry/NCT05361083.

Keywords: Adrenal tracer; Positron emission tomography; [18F]CETO.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1

[18F]CETO coronal (top) and transaxial (bottom) images at 5, 15, 30 and 60 min p.i. and whole-body images at 2, 3 and 5 hours p.i.

Fig. 2

Time-activity-curves (TACs) showing the mean SUVmean of [18F]CETO versus time post injection (x-axis). a: Normal organs/tissues b: Non-functioning adrenal adenoma, calcified), Non-functioning adrenal adenoma, Cortisol producing adenoma, aldosterone-producing adenoma/Adrenal hyperplasia, Myelolipoma, Adrenocortical carcinoma (ACC) recurrence and normal adrenal tissue. Patients with calcified non-functioning adenoma and ACC only underwent a single whole-body scan, hence no data at later time points was available

Fig. 3

ACC metastasis(arrow), patient 11. [18F]CETO PET 3 hours post injection (a) and venous phase contrast-enhanced CT performed 17 days before [18F]CETO PET (b). A high uptake of [18F]CETO is seen in the ACC metastasis (a)

Fig. 4

Right-sided Conn adenoma (arrow), patient 4. [18F]CETO PET 3 h post injection (a), arterial phase contrast-enhanced CT (b), and venous phase contrast-enhanced CT (c) where CT was performed 6 months before [18F]CETO PET

Fig. 5

Left-sided adrenal Cushing(arrow), patient 3. [18F]CETO PET 3 h post injection (a), arterial phase contrast-enhanced CT (b), and venous phase contrast-enhanced CT (c), where CT was performed 3 days after [18F]CETO PET

Fig. 6

Bilateral nonfunctional adenomas(arrows), patient 15. [18F]CETO PET 3 h post injection (a) and CT (b), where CT was performed 17 days before [18F]CETO PET

Fig. 7

a Typical blood-derived and image-derived whole-blood time-activity curves, b mean fraction of intact tracer (N = 14) and c mean plasma-whole blood ratio (N = 15). The data from a, b, and c, multiplied together, equals the input function

Fig. 8

Relationship between K1 from the 1T1k compartment model using an IDIF (a) and an IDIF-PA (b). Black line equal to the line of identity

Fig. 9

K1 from the 1T1k compartment model against SUV60–70 (a) and SUV120 (b) for adenomas (solid circles), normal adrenal tissue in patients (open circles), and healthy volunteers (blue triangles)

Fig. 10

[18F]CETO K1-1T1k versus blood flow in the adrenal gland. Test and retest values in both adrenals are included. The solid line is a linear regression

Fig. 11

K1-1T1k (a), SUV60–70 (b), and SUV120 (c) in healthy controls, normal adrenals in patients, Cushing, NFA and PA. c. controls, n. normal, p. patients The asterisk denotes significant difference (Mann-Whitney test)