123I-Iodometomidate for molecular imaging of adrenocortical CYP11B enzymes

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ABSTRACT:

 

[123I]Iodometomidate for Molecular Imaging of Adrenocortical Cytochrome P450 Family 11B Enzymes

Stefanie Hahner1, Andrea Stuermer1, Michael Kreissl, Christoph Reiners, Martin Fassnacht, Heribert Haenscheid, Felix Beuschlein, Martina Zink, Katharina Lang, Bruno Allolio1 and Andreas Schirbel1

Endocrinology and Diabetes Unit (S.H., A.St., M.F., M.Z., K.L., B.A.), Department of Medicine I, and Department of Nuclear Medicine (M.K., C.R., H.H., A.Sc.), University of Wuerzburg, D-97080 Wuerzburg, Germany; and Medical Clinic (F.B.), University Hospital Innenstadt, Ludwig Maximilians University, D-80336 Munich, Germany

 

Address all correspondence and requests for reprints to: Prof. Dr. Bruno Allolio, M.D., Endocrinology and Diabetes Unit, Department of Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg, Germany. E-mail: allolio_b@medizin.uni-wuerzburg.de.

 

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 [123/125I]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 [123I]iodometomidate-SPECT.

 

Results: In cell culture experiments, all compounds potently inhibited both Cyp11B1 and Cyp11B2. Adrenals showed high and specific uptake of [123/125I]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 [123I]IMTO scintigraphy in both experimental animals and humans. Our findings suggest that [123I]IMTO is a highly specific radiotracer for imaging of adrenocortical tissue. Due to the general availability of SPECT technology, we anticipate that [123I]IMTO scintigraphy may become a widely used tool to characterize adrenal lesions.

 

I'm wondering if this would be helpful for adrenal rest tissue???

 

Hugs,

Robin

[Jo MacRaild]

Great article Robin, thanks. from my read..it picks up tissue that can potentially emit aldosterone or cortisol , via the precurser CYP enzymes so yes, great for finding rest tissue, & ectopic & metatastic adrenal tissue. ( I didn't know you could get that, well I knew they could spread, but not that the spread tissue was adrenal in origin... ) Not quite sure, on the carcinoid stuff, I got a bit cornfused there..

 

What a breakthrough, anyone had spect ? or PET ? I know they use octreotide , with PET, as its taken up by tumors that do there thing to GH..& inversely octreotide can treat them. Interesting they're making the jump to treatment suggestions for IMTO too.

 

 

Hurray for advancing science.

[chanceofrain]

I sure hope this works bc the only other good test was the idocholesterol test and UofM was the only place that made the isotope and they stopped like 2 years ago.