[123I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes
Abstract
BACKGROUND: Due to advances in conventional imaging, adrenal tumors are detected with increasing frequency. However, conventional imaging provides only limited information on the origin of these lesions, which represent a wide range of different pathological entities. New specific imaging methods would therefore be of great clinical value. We, therefore, studied the potential of iodometomidate (IMTO) as tracer for molecular imaging of cytochrome P450 family 11B (Cyp11B) enzymes. METHODS: Inhibition of Cyp11B1 and Cyp11B2 by IMTO, etomidate, metomidate, and fluoroetomidate was investigated in NCI-h295 cells and in Y1 cells stably expressing hsCyp11B1 or hsCyp11B2. Pharmacokinetics and biodistribution after iv injection of [(123/125)I]IMTO were analyzed in mice in biodistribution experiments and by small-animal single-photon emission computed tomography (SPECT). Furthermore, four patients with known adrenal tumors (two metastatic adrenal adenocarcinomas, one bilateral adrenocortical adenoma, and one melanoma metastasis) were investigated with [(123)I]iodometomidate-SPECT. RESULTS: In cell culture experiments, all compounds potently inhibited both Cyp11B1 and Cyp11B2. Adrenals showed high and specific uptake of [(123/125)I]IMTO and were excellently visualized in mice. In patients, adrenocortical tissue showed high and specific tracer uptake in both primary tumor and metastases with short investigation time and low radiation exposure, whereas the non-adrenocortical tumor did not exhibit any tracer uptake. CONCLUSION: We have successfully completed the development of an in vivo detection system of adrenal Cyp11B enzymes by [(123)I]IMTO scintigraphy in both experimental animals and humans. Our findings suggest that [(123)I]IMTO is a highly specific radiotracer for imaging of adrenocortical tissue. Due to the general availability of SPECT technology, we anticipate that [(123)I]IMTO scintigraphy may become a widely used tool to characterize adrenal lesions.
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[123I]IMTO single-photon emission CT imaging showed high tracer uptake in tissue of adrenocortical origin.
“[123I]IMTO single-photon emission CT imaging showed high tracer uptake in tissue of adrenocortical origin (110), suggesting that [131I]IMTO represents a suitable compound for targeted radionuclide therapy.”
From Adrenocortical carcinoma (2014) · cites this paper as [110]
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- Authors
- Hahner, S., Stuermer, A., Kreissl, M., Reiners, C., Fassnacht, M., Haenscheid, H., Beuschlein, F., Zink, M., Lang, K., Allolio, B., & Schirbel, A.
- Affiliations
- University of Würzburg (DE)
- LMU Klinikum (DE)
- Corresponding author
- Allolio, Bruno
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-06-01
- Volume
- 93
- Issue
- 6
- Pages
- 2358-2365
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2104149388
- Cited by
- 95
- References
- 28
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 7 · 2016: 9 · 2015: 4 · 2014: 7 · 2013: 9 · 2012: 8
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- CYP11B1, CYP11B2, adrenal tumors, adrenal metastasis, adrenal adenocarcinoma, adrenal adenoma, melanoma metastasis, radiotracer development, SPECT imaging, enzyme inhibition, NCI-H295 cells, Y-1 cells, tissue distribution, pharmacokinetics
- MeSH terms
- Adrenal Cortex, Adrenal Cortex Neoplasms, Aged, Animals, Cells, Cultured, Etomidate, Female, Multigene Family, Humans, Iodine Radioisotopes, Male, Middle Aged, Radioactive Tracers, Steroid 11-beta-Hydroxylase, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Adrenocortical Carcinoma, Cytochrome P-450 CYP11B2, Molecular Diagnostic Techniques, Mice, Whole Body Imaging
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