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 as tracer for molecular imaging of Cyp11B enzymes.

Methods: Inhibition of Cyp11B1 and Cyp11B2 by iodometomidate, etomidate, metomidate and fluoroetomidate was investigated in NCI-h295 cells and in Y1 cells stably expressing hsCyp11B1 or hsCyp11B2. Pharmakokinetics and biodistribution after i.v.-injection of [^{123, 125}I]iodometomidate were analyzed in mice in biodistribution experiments and by small animal SPECT. Furthermore, four patients with known adrenal tumors (2 metastatic ACC, 1 bilateral adrenocortical adenoma, 1 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, 125}I]iodometomidate 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 nonadrenocortical 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 iodometomidate ([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.