Para-chloro-2-[¹⁸F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging

Abstract

Introduction: [ 11 C]Metomidate ([ 11 C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [ 11 C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T 1/2 =109.5 min) etomidate analogue, para-chloro-2-[ 18 F]fluoroethyl etomidate; [ 18 F]CETO, as an adrenal PET tracer. Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [ 18 F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [ 11 C]MTO. Results: The binding of [ 18 F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro K d of 0.66 nM. Non-specific uptake of [ 18 F]CETO in NHP liver was found to be low compared to that of [ 11 C]MTO. Conclusions: High specificity of [ 18 F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [ 11 C]MTO. Non-specific binding to the liver was significantly lower than that of [ 11 C]MTO. [ 18 F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.

[11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial

“…The main limitation of [ 11 C]MTO is its 20-min half-life, which requires synthesis by an on-site cyclotron. 18 F ligands, with a 2-h half-life, are currently under evaluation (NCT04529018), with the potential for molecular imaging to become available in all PA centers 40 .…”

“…Unlike AVS, MTO is quick, safe and reliable. These advantages may attract more clinicians and patients to seek a diagnosis, especially if the 18 F analog becomes available and transportable to most hospitals with PET imaging facilities 40 .…”

Clinical utility of nuclear imaging in the evaluation of pediatric adrenal neoplasms

“…The successful synthesis of PET-based NP-59 radiopharmaceutical, 18 F-NP-59, and its superior imaging characteristics and reduced radiation dose compared to that of 131 I-NP-59 will likely lead to NP-59’s adoption for adrenal cortex imaging in the future ( 43 ). In this situation, PET radiopharmaceuticals that target the CYP11B enzyme family are of interest and can reduce radiation dose exposure but have limited availability ( 44 , 45 ).…”

Adrenal functional imaging – which marker for which indication?

“…When compared to carbon-11, fluorine-18 radiochemistry has multiple advantages, including its longer half-life and higher positron yield, thereby allowing for radiotracer supply of distant PET sites without regular access to a cyclotron facility [20,21]. Initial preclinical experiments with the 11b-hydroxylase inhibitors 2-[ 18 F]fluoroethyl-etomidate ([ 18 F] FETO) [22], the para-fluorinated aromatic (R)-MTO derivative ([ 18 F]FAMTO) [23], and para-chloro-2-[ 18 F]fluoroethyl-etomidate ([ 18 F]CETO) [24] showed promising results with a remarkable selectivity towards aldosterone-producing enzymes, including 11b-hydroxylase/aldosterone synthase (CYP11B1/ B2). Those studies, however, have been primarily conducted in a preclinical environment and thus, human prospective studies are underway to demonstrate the superior diagnostic performance of CYP11B1/B2-targeting radiotracers in the clinic [25].…”