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Non-FDG radionuclide imaging and targeted therapies
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Luigi Aloj, Ferdia A Gallagher
Characterization of adrenal lesions is often a diagnostic dilemma in radiology, particularly if they are small. It is important to be able to distinguish benign disease from both primary adrenal malignancy and metastases (77). Cortisol and steroid hormone metabolism is specific to the adrenal cortex and gonads. Labelled precursors of steroid hormones have long been utilized to image and characterize adrenal masses to identify the tissue of origin. 131I-labelled cholesterol derivatives have been utilized since the 1970s for this purpose, using standard gamma camera imaging (78). 11ß-hydroxylase is an essential enzyme in the biosynthesis of cortisol and aldosterone, which is overexpressed in adrenocortical adenomas. Metomidate is an inhibitor of the enzyme 11β hydroxylase, and several metomidate derivatives have been used to identify and characterize adrenocortical lesions. Iodo-metomidate tracers have shown promise for the diagnosis and management of adrenocortical carcinoma (79), and increasingly, 11C-metomidate PET-CT has been shown to have a role in primary hyperaldosteronism or Conn's syndrome, where it can replace the need for invasive adrenal vein sampling (80,81). While such studies can only be performed in a specialized centre, it demonstrates the potential for these highly selective tracers in stratified patient populations. An example of the use of 11C-metomidate is given in Figure 44.8.
Endocrine hypertension
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
Frances McManus, John M. Connell, Marie Freel
Given these difficulties, the prospect of another tool to differentiate unilateral, surgically curable disease from bilateral disease is appealing. The use of 11C-metomidate as a radiotracer in positron emission tomography (PET)-CT could be useful in this situation. Recent data have demonstrated sensitivity and specificity of 76% (CI 59–93) and 87% (CI 69–104) using this noninvasive technique that requires less technical expertise.28 The use of 11C-metomidate PET is be limited to centers with access to a cyclotron, but this promising diagnostic test may be used more frequently in the future.
Image-based computer modeling assessment of microwave ablation for treatment of adrenal tumors
Published in International Journal of Hyperthermia, 2022
Jan Sebek, Grazia Cappiello, George Rahmani, Nooshin Zeinali, Muireann Keating, Michael Fayemiwo, Jim Harkin, Liam McDaid, Bryan Gardiner, Declan Sheppard, Russell Senanayake, Mark Gurnell, Martin O’Halloran, M. Conall Dennedy, Punit Prakash
11C-Metomidate PET/CT was performed at Addenbrooke’s Hospital Cambridge. All patients were pretreated with 0.5 mg dexamethasone 6 hourly for 72 h prior to scanning [28,29]. 11C-Metomidate was manufactured on site in compliance with good manufacturing practice using a GE Medical Systems PETtrace cyclotron (Milwaukee, WI), as previously described [29].
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Published in Expert Opinion on Drug Discovery, 2019
Bernd Antkowiak, Gerhard Rammes
Etomidate-induced suppression of adrenocortical steroid synthesis turned out to be of great concern since supplemental steroids did not improve the outcome of septic shock patients suffering from adrenal insufficiency [59]. On this background it is not surprising that approaches to develop etomidate analogs for clinical use aim to attenuate adrenal toxicity. One strategy to mitigate this side effect is to create analogs that are rapidly metabolized. These ‘soft’ analogs still would produce adrenocortical suppression but allow rapid recovery after their administration is discontinued. Methoxycarbonyl (MOC)-etomidate was a prototype of a series of soft etomidate derivatives. Similar to remifentanil, it contains a metabolically labile ester component that is rapidly cleaved by esterases. In the case of MOC-etomidate, the ester moiety was appended by a two-carbon spacer in order to affect the hypnotic action of etomidate as little as possible. MOC-etomidate showed hypnotic properties during animal testing, but was less potent than etomidate [60]. After bolus injection, the hypnotic effect was extremely brief and adrenocortical toxicity was not detectable [61]. However, after longer infusions accumulation of metabolites markedly slowed recovery from anesthesia [62]. Although MOC-etomidate was not advanced to clinical use, this agent provided proof-of-principle that etomidate analogs can be created that do not persistently suppress adrenocortical function. Further etomidate analogs were developed, differing only in the structure of the spacer, to tackle the issue of metabolite accumulation. During animal testing, cyclopropyl-methoxycarbonyl metomidate (CPMM) was identified as the most promising compound. Its hypnotic potency was similar to that of etomidate and it was rapidly metabolized, but slower than MOC-etomidate [63]. Continuous infusion of CPMM produced adrenocortical suppression, but recovery was significantly faster than after etomidate [64]. Recent in-human-studies showed that the compound was safe and well tolerated and did neither cause severe hypotension, nor respiratory or adrenocortical suppression [65,66]. ET-26 hydrochloride is another etomidate soft analog that was successfully tested in rats but human studies are pending [67].