[123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes.
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.


CONCLUSIONS
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.
Hahner
Stefanie
S
Endocrinology and Diabetes Unit, Department of Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg, Germany.
Stuermer
Andrea
A
Kreissl
Michael
M
Reiners
Christoph
C
Fassnacht
Martin
M
Haenscheid
Heribert
H
Beuschlein
Felix
F
Zink
Martina
M
Lang
Katharina
K
Allolio
Bruno
B
Schirbel
Andreas
A
D000302:Adrenal Cortex / Q000201:enzymology / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2 / Q000032:analysis* / Q000235:genetics; D005045:Etomidate / Q000031:analogs & derivatives / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D005810:Multigene Family; D011849:Radioactive Tracers; D013252:Steroid 11-beta-Hydroxylase / Q000032:analysis* / Q000235:genetics; D051598:Whole Body Imaging / Q000379:methods
D007457:Iodine Radioisotopes; D011849:Radioactive Tracers; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; C084586:metomidate; D005045:Etomidate