[18F]FETO: metabolic considerations

Ettlinger, Dagmar E.; Wadsak, Wolfgang; Mien, Leonhard‐Key; Machek, Michael; Wabnegger, Leila; Rendl, Gundula; Karanikas, Georgios; Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert; Mitterhauser, Markus

doi:10.1007/s00259-006-0123-5

Cited by 19 publications

(12 citation statements)

References 7 publications

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“…In many cases, 2-[ 18 F]fluoroethanol [ 18 F] 3a or its metabolites 2-[ 18 F]fluoroacetaldehyde [ 18 F] 3b and 2-[ 18 F]fluoroacetate [ 18 F] 3c have been observed during metabolic degradation of several PET tracers containing a 2-[ 18 F]fluoroethyl group such as [ 18 F]FECNT [ 18 F] 7 [45], [ 18 F]FETO [ 18 F] 8 [46], [ 18 F]FDDNP [ 18 F] 9 [47], [ 18 F]FFMZ [ 18 F] 10 [48], and [ 18 F]FERhB [ 18 F] 11 [49]. The metabolites (presumably 2-[ 18 F]fluoroacetaldehyde [ 18 F] 3b and 2-[ 18 F]fluoroacetate [ 18 F] 3c ) from N -defluoroethylation of [ 18 F]FECNT [ 18 F] 7 and [ 18 F]FDDNP [ 18 F] 9 have been shown to distribute evenly in the brain, confounding data analysis [46,47]. The metabolic behavior of [ 18 F]FECNT [ 18 F] 7 is shown in Scheme 4.…”

Section: Radiodefluorinationmentioning

confidence: 99%

Methods to Increase the Metabolic Stability of 18F-Radiotracers

2015

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Abstract:The majority of pharmaceuticals and other organic compounds incorporating radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Metabolic degradation of these drugs is commonly caused by a system of enzymes of low substrate specificity requirement, which is present mainly in the liver, but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo highlighting the importance of their structure. Often in practice, such biologically active molecules exhibit these properties in vitro, but fail during in vivo studies due to obtaining an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds never see application due to their lack of stability. One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of

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Section: Radiodefluorinationmentioning

confidence: 99%

Methods to Increase the Metabolic Stability of 18F-Radiotracers

2015

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“…In addition, an 18 F-etomidate analogue, 2-[ 18 F]fluoroethyl-desethyl-( R )-etomidate ( 18 F-FETO), has been evaluated in several in vitro and in vivo studies [52,53,54]. 18 F-FETO exhibits high affinity binding to the target enzymes, similar stability to metomidate and etomidate against esterases, and fast in vivo metabolism.…”

Section: 123/124/131i-iodometomidate Imaging In Adrenal Diseasementioning

confidence: 99%

Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

et al. 2016

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Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism.

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“…Both compounds also accumulate in the lung, pancreas and liver, further indicating rapid metabolism in line with earlier metabolism data. 19 …”

Section: Analysis Of Radiolabelled Metabolites In Plasmamentioning

confidence: 97%

Synthesis and in vitro evaluation of ¹⁸F‐labelled di‐ and tri(ethylene glycol) metomidate esters

Erlandsson

Hall

Långström

2009

Labelled Comp Radiopharmac

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By replacing the alkyl chain in a metomidate ester with 18 F]fluorination reactions using conventional and microwave heating. Organ distribution, frozen section autoradiography and metabolite analysis were performed. The decay-corrected radiochemical yields of 1 and 2 were 2678 and 2378%, respectively, when they were prepared using conventional heating. By performing microwave heating, the reaction time could be decreased and the yields of analogues 1 and 2 could be increased to 57712 and 51718%, respectively. Organ distribution studies in the rat showed considerable uptake in the lungs, adrenals and liver. Both compounds bound with low nonspecific binding (1: approx. 20-30%; 2: 2.9% or lower) to tissue from pig and human normal and pathologic adrenals. Metabolite analyses were performed in rats after 5 and 30 min for tracer 1 (2076 and 271%) and tracer 2 (2775 and 674%). Both compounds are interesting candidates for the detection of different types of adrenal disorders.

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[18F]FETO: metabolic considerations

Abstract: In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast.

Cited by 19 publications

References 7 publications

Methods to Increase the Metabolic Stability of 18F-Radiotracers

Methods to Increase the Metabolic Stability of 18F-Radiotracers

Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

Synthesis and in vitro evaluation of ¹⁸F‐labelled di‐ and tri(ethylene glycol) metomidate esters

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[18F]FETO: metabolic considerations

Abstract: In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast.

Cited by 19 publications

References 7 publications

Methods to Increase the Metabolic Stability of 18F-Radiotracers

Methods to Increase the Metabolic Stability of 18F-Radiotracers

Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

Synthesis and in vitro evaluation of 18F‐labelled di‐ and tri(ethylene glycol) metomidate esters

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About

Synthesis and in vitro evaluation of ¹⁸F‐labelled di‐ and tri(ethylene glycol) metomidate esters