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Filippo Crimì, Alessandro Spimpolo, Diego Cecchin, Gian Paolo Rossi, Functional imaging by 11C-metomidate PET: a really useless technique for primary aldosteronism subtyping?, European Journal of Endocrinology, Volume 184, Issue 3, Mar 2021, Pages L9–L10, https://doi.org/10.1530/EJE-20-1402
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Dear Editor,
Soinio et al. (1) recently compared the diagnostic accuracy of 11C-metomidate PET (11C-MTO-PET) and cosyntropin-stimulated adrenal venous sampling (AVS) for the subtyping of patients with primary aldosteronism (PA), who were diagnosed according to the 2008 Endocrine Society guidelines (2). Metomidate, the methyl ester of 1-[(1R)-1phenylethyl]-1H-imidazol-5-carboxylic acid, inhibits both steroid-11-beta-hydroxylase (CYP11B1) and aldosterone-synthase (CYP11B2) in human adrenocortical tissues with similar IC50 (0.24 vs 0.6 nM) (3). Because of this poor selectivity, the compound was not further considered as a therapeutic tool to decrease high plasma aldosterone in humans. However, it was pursued for functional imaging based on promising results in pilot studies (4, 5).
Soinio et al. concluded that 11C-MTO-PET offered no diagnostic usefulness in PA patients. In our view, this conclusion needs to be taken with great caution owing to a number of concerns that can be raised concerning their study.
First, notwithstanding the poor selectivity for CYP11B2, they performed 11C-MTO-PET without prior suppression of background uptake of the radiotracer in the glucocorticoid-producing zona fasciculata of the normally functioning adrenocortical tissue adjacent to an aldosterone-producing adenoma (APA) by means of dexamethasone administration (5). This is, in our view, of key importance in order to avoid excess background radiotracer uptake inasmuch as 11C-MTO binds also to CYP11B1, which is widely expressed in the adrenocortical tissue (6). Accordingly, in previous studies on 11C-MTO-PET, which highlighted its potential for functional imaging of PA, dexamethasone suppression was systematically administered (4, 5). The lack of background suppression could explain the low SUVmax-ratio cutoff of 1.16 identified by Soinio et al. (1) in their ROC curve analysis, as compared to the 1.25 found by Burton (5) and used by O'Shea (4).
