Targeted Molecular Imaging in Adrenal Disease-An Emerging Role for Metomidate PET-CT

Abstract

Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal 'incidentalomas' detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing's syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of ¹¹C-metomidate PET-CT in primary aldosteronism.

Keywords: adrenal; adrenocortical carcinoma; metomidate; nuclear medicine; primary aldosteronism.

Figure 1

Illustrative case 1: A 65-year-old man with a ten-year history of hypertension and hypokalaemia, requiring multiple agents for blood pressure control (including eplerenone) and oral potassium supplementation, was diagnosed with primary aldosteronism. CT demonstrated a lipid-poor 12 mm left adrenal nodule - displayed in axial, coronal and sagittal planes (a–c). ¹¹C-metomidate PET-CT [(d–f) (PET) and (g–i) (PET-CT)] confirmed increased tracer uptake in the left adrenal nodule. The patient underwent laparoscopic left adrenalectomy, with subsequent histology confirming a classical Conn’s adenoma. Post-operatively, he had complete resolution of his hyperaldosteronism with excellent blood pressure control on progressive down-titrating medications (currently two agents with further weaning planned), and with no requirement for supplemental potassium at four-month follow-up. For comparison, axial PET/PET-CT images are shown as reconstructed via “time-of-flight” (TOF) iterative algorithms: without (j,k) and with resolution modeling (SharpIR) (l,m).

Figure 2

Illustrative case 2: A 55-year-old man with a five-year history of refractory hypertension and hypokalaemia (requiring four agents for blood pressure control) was diagnosed with primary aldosteronism (PA); CT demonstrated a 16mm left adrenal nodule (a–c), which was ¹¹C-metomidate avid, confirming unilateral PA (d–i). Functional imaging was performed after right adrenal vein cannulation had been unsuccessful during adrenal vein sampling. A left laparoscopic adrenalectomy confirmed a typical Conn’s adenoma. Three years post-operatively his PA remains in complete remission and he requires only a single agent (amlodipine) to achieve full blood pressure control.

Figure 3

Illustrative case 3: A 42-year-old woman had been diagnosed with hypertension and hypokalaemia 15 years previously in pregnancy. She rotated through trials of various anti-hypertensive medications before achieving reasonable control with spironolactone, together with additional potassium supplementation. A biochemical diagnosis of primary aldosteronism was made following a failure to suppress aldosterone on a saline infusion test. CT findings were equivocal, but with a suggestion of possible subcentimetre nodules bilaterally on CT (a). There were no discrete ‘hot nodules’, with symmetrical bilateral uptake on ¹¹C-metomidate PET-CT (b,c). Her bilateral disease is currently managed medically.

Figure 4

Illustrative case 4: A 40-year-old man with a five-year history of hypertension and hypokalaemia had a diagnosis of hyperaldosteronism confirmed by failure to suppress aldosterone following saline infusion. CT findings were equivocal, showing a possible small right adrenal nodule (a). Tracer uptake was symmetrical bilaterally on ¹¹C-metomidate PET-CT (b,c). His bilateral disease is managed medically.