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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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1-(1-Phenylethyl)-1H-imidazole-5-carboxylic acid [11C]methyl ester

[11C]MTO
, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: July 18, 2005.

Chemical name:1-(1-Phenylethyl)-1H-imidazole-5-carboxylic acid [11C]methyl esterimage 3131788 in the ncbi pubchem database
Abbreviated name:[11C]MTO
Synonym:[11C]Metomidate, [O-Methyl-11C]Metomidate
Agent category:Compound
Target:11β-Hydroxylase
Target category:Enzyme
Method of detection:Positron emission tomography (PET)
Source of signal:11C
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
  • Checkbox Non-human primates
  • Checkbox Humans
Click on the above structure for additional information in PubChem.

Background

[PubMed]

In the adrenocortex, 11β-hydroxylase is a key enzyme in the biosynthesis of cortisol and aldosterone. This enzyme can be overexpressed in adrenocortical carcinomas, which secrete excessive amounts of catecholamines and cortical hormone (1). However, some adrenal tumors appear unexpectedly as incidentalomas in computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound scans in 1-4% of patients (2). Most of these incidentalomas consist of benign, cortical, nonhypersecretory adenomas (3). Therefore, it is important to identify the malignant lesions in the incidentalomas for appropriate clinical treatments. Ketoconazole, etomidate and metomidate are potent inhibitors of 11β-hydroxylase (4, 5). [11C]Metomidate introduced as an adrenocortical imaging tracer by Bergstrom et al. (6) has proven to be useful in distinguishing adrenocortical from non-cortical lesions and identifying incidentalomas of adrenocortical origin (7-10).

Synthesis

[PubMed]

[11C]MTO was first synthesized by reacting (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid with [11C]methyl iodide with low recovery yields by preparative high-performance liquid chromatography (HPLC) (6). The specific activity was up to 120 GBq/μmol (3.2 Ci/μmol). Later, [11C]MTO was purified with an improved preparative HPLC method to >99% radiochemical purity (11). The overall yield was 19.9% (not decay corrected, based on [11C]methyl iodide) in 34 min. The specific activity was up to 63.3 GBq/μmol (1.71 Ci/μmol) averaging 14.4 GBq/μmol (0.389 Ci/μmol).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

In vitro frozen section autoradiography with [11C]MTO in different tissues from rats and pigs were measured (6). The adrenals have the highest uptake, followed by the livers (26% of adrenal uptake). The uptake by pig adrenal slices linearly increased with time. A plateau was seen at about 40-50 min. The nonspecific binding was 2% for [11C]MTO and 13% for [11C]etomidate. [11C]MTO (30 nm) binding to pig adrenal cortex was inhibited by etomidate with an IC50 of 0.4 μm. Etomidate inhibited the [11C]MTO binding to liver slices with an IC50 of 0.07 μm. There was a clear correlation of 11β-hydroxylase staining to [11C]MTO binding in different tissue slices. Human adenomas showed strong 11β-hydroxylase staining and high [11C]MTO binding (1.40 ± 0.76) as compared with nonadrenal cancers with weak staining and low binding (0.17 ± 0.15).

Animal Studies

Rodents

[PubMed]

No relevant publication is currently available.

Other Non-Primate Mammals

[PubMed]

No relevant publication is currently available.

Non-Human Primates

[PubMed]

Positron emission tomography (PET) studies in three rhesus monkeys showed high uptake of [11C]MTO in the adrenals with excellent visualization (6). The uptake increased with time without washout at 45 min after injection. Slightly lower uptake was seen in the liver as compared with the adrenals. No other organs besides the adrenals and livers have any uptake at 45 min.

Human Studies

[PubMed]

[11C]MTO PET was performed in 15 patients with unilateral adrenal lesions as confirmed by CT (12). [11C]MTO (294-938 MBq, 8-25 mCi) was intravenously injected into patients. All cortical lesions were easily visualized with high tracer uptake, whereas the noncortical lesions showed very low uptake at 5 to 40 min after injection. High uptake was seen in the stomach, normal adrenals, and liver. The kidney and spleen reached a moderate uptake within a few min after injection and then declined rapidly to almost background levels.

[11C]MTO PET studies were performed in 11 patients with CT-detected primary tumors or recurrence and/or metastases from a previously histopathologically proven adrenocortical carcinoma The PET findings were compared with the CT scan findings and verified by histopathology. Primary adrenocortical carcinoma showed increased [11C]MTO uptake compared with normal adrenal, liver, and other normal tissues (such as the spleen, kidney, and muscle). The high liver metastasis to normal liver background ratio contributed to the better sensitivity of tumor detection by PET. When all visible lesions were considered, uptake (SUV, 16.4 ± 2.2) was higher than in adrenals (SUV, 11.5 ± 1.5; p < 0.02), liver (SUV, 8.9 ± 0.9; p < 0.005), spleen, kidney, and muscle (all, p < 0.001). Normal adrenal had higher uptake than liver (p < 0.02) and all other normal tissues (p < 0.001), whereas liver showed higher uptake than all other normal organs except adrenal (p < 0.0001). It was noted that chemotherapy and treatment with adrenal steroid inhibitors decreased [11C]MTO uptake and may interfere with lesion detection.

[11C]MTO PET studies were performed recently in 21 patients with adrenal incidentalomas (9) and in 16 patients with adrenocortical lesions (10). Both studies concluded that [11C]MTO uptake was able to distinguish between adrenocortical and nonadrenocortical lesions. FDG was found to be a better PET tracer than [11C]MTO in distinguishing between benign and malignant adrenal lesions. Internal dosimetry data for [11C]MTO in humans is not available in the literature.

References

1.
Suzuki H., Shibata H., Maruyama T., Ishimura Y., Saruta T. Significance of steroidogenic enzymes in the pathogenesis of hyperfunctioning and non-hyperfunctioning adrenal tumor. Steroids. 1995;60(1):42–7. [PubMed: 7792814]
2.
Bertherat J., Mosnier-Pudar H., Bertagna X. Adrenal incidentalomas. Curr Opin Oncol. 2002;14(1):58–63. [PubMed: 11790982]
3.
Kloos R.T., Gross M.D., Francis I.R., Korobkin M., Shapiro B. Incidentally discovered adrenal masses. Endocr Rev. 1995;16(4):460–84. [PubMed: 8521790]
4.
Engelhardt D. Steroid biosynthesis inhibitors in Cushing's syndrome. Clin Investig. 1994;72(7):481–8. [PubMed: 7981573]
5.
Varga I., Racz K., Kiss R., Futo L., Toth M., Sergev O., Glaz E. Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells. Steroids. 1993;58(2):64–8. [PubMed: 8387232]
6.
Bergstrom M., Bonasera T.A., Lu L., Bergstrom E., Backlin C., Juhlin C., Langstrom B. In vitro and in vivo primate evaluation of carbon-11-etomidate and carbon-11-metomidate as potential tracers for PET imaging of the adrenal cortex and its tumors. J Nucl Med. 1998;39(6):982–9. [PubMed: 9627330]
7.
Bergstrom M., Sorensen J., Kahn T.S., Juhlin C., Eriksson B., Sundin A., Bonasera T.A., Fasth K., Langstrom B. PET with [11C]-Metomidate for the Visualization of Adrenocortical Tumors and Discrimination from Other Lesions. Clin Positron Imaging. 1999;2(6):339. [PubMed: 14516636]
8.
Khan T.S., Sundin A., Juhlin C., Langstrom B., Bergstrom M., Eriksson B. 11C-metomidate PET imaging of adrenocortical cancer. Eur J Nucl Med Mol Imaging. 2003;30(3):403–10. [PubMed: 12634969]
9.
Minn H., Salonen A., Friberg J., Roivainen A., Viljanen T., Langsjo J., Salmi J., Valimaki M., Nagren K., Nuutila P. Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG. J Nucl Med. 2004;45(6):972–9. [PubMed: 15181132]
10.
Zettinig G., Mitterhauser M., Wadsak W., Becherer A., Pirich C., Vierhapper H., Niederle B., Dudczak R., Kletter K. Positron emission tomography imaging of adrenal masses: (18)F-fluorodeoxyglucose and the 11beta-hydroxylase tracer (11)C-metomidate. Eur J Nucl Med Mol Imaging. 2004;31(9):1224–30. [PubMed: 15197504]
11.
Mitterhauser M., Wadsak W., Langer O., Schmaljohann J., Zettinig G., Dudczak R., Viernstein H., Kletter K. Comparison of three different purification methods for the routine preparation of [11C] Metomidate. Appl Radiat Isot. 2003;59(2-3):125–8. [PubMed: 12941500]
12.
Bergstrom M., Juhlin C., Bonasera T.A., Sundin A., Rastad J., Akerstrom G., Langstrom B. PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate. J Nucl Med. 2000;41(2):275–82. [PubMed: 10688111]

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