Hahner Stefanie, Stuermer Andrea, Kreissl Michael, Reiners Christoph, Fassnacht Martin, Haenscheid Heribert, Beuschlein Felix, Zink Martina, Lang Katharina, Allolio Bruno, Schirbel Andreas
Endocrinology and Diabetes Unit, Department of Medicine, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg, Germany.
J Clin Endocrinol Metab. 2008 Jun;93(6):2358-65. doi: 10.1210/jc.2008-0050. Epub 2008 Apr 8.
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.
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.
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.
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.
由于传统成像技术的进步，肾上腺肿瘤的检出频率越来越高。然而，传统成像仅能提供关于这些病变起源的有限信息，这些病变代表了广泛的不同病理实体。因此，新的特异性成像方法具有重要的临床价值。我们因此研究了碘美托咪酯（IMTO）作为细胞色素P450 11B（Cyp11B）酶分子成像示踪剂的潜力。
在NCI-h295细胞以及稳定表达hsCyp11B1或hsCyp11B2的Y1细胞中，研究了IMTO、依托咪酯、美托咪酯和氟乙托咪酯对Cyp11B1和Cyp11B2的抑制作用。在生物分布实验中，通过小鼠体内注射[(123/125)I]IMTO后的药代动力学和生物分布情况，以及通过小动物单光子发射计算机断层扫描（SPECT）进行分析。此外，对4例已知肾上腺肿瘤患者（2例转移性肾上腺腺癌、1例双侧肾上腺皮质腺瘤和1例黑色素瘤转移）进行了[(123)I]碘美托咪酯-SPECT检查。
在细胞培养实验中，所有化合物均能有效抑制Cyp11B1和Cyp11B2。肾上腺显示出[(123/125)I]IMTO的高特异性摄取，并且在小鼠体内能清晰显影。在患者中，肾上腺皮质组织在原发性肿瘤和转移灶中均显示出高特异性示踪剂摄取，检查时间短且辐射暴露低，而非肾上腺皮质肿瘤未显示任何示踪剂摄取。
我们已通过[(123)I]IMTO闪烁扫描成功完成了实验动物和人类体内肾上腺Cyp11B酶检测系统的开发。我们的研究结果表明，[(123)I]IMTO是用于肾上腺皮质组织成像的高度特异性放射性示踪剂。由于SPECT技术的广泛应用，我们预计[(123)I]IMTO闪烁扫描可能会成为一种广泛用于肾上腺病变特征化的工具。
