What is the role of a Gallium (Ga) 68 pentixafor scan in diagnosing adrenal adenoma when a computed tomography (CT) scan is non-conclusive?

Gallium-68 Pentixafor PET/CT Has No Established Role in Diagnosing Adrenal Adenomas

Gallium-68 pentixafor PET/CT is not recommended for evaluating indeterminate adrenal adenomas, as it is a specialized tracer for primary aldosteronism (specifically aldosterone-producing adenomas) and has no validated role in distinguishing benign adenomas from other adrenal pathology when CT is non-conclusive.

Standard Approach for Non-Conclusive CT

When initial CT imaging is indeterminate for adrenal adenoma characterization, established guidelines provide clear second-line options:

Recommended Second-Line Imaging

• Delayed enhancement (washout) CT should be performed if the non-contrast CT shows >10 HU, with adenomas demonstrating >60% absolute washout or >40% relative washout at 15 minutes 1, 2
• Chemical shift MRI is equally appropriate as second-line imaging, exploiting microscopic fat detection with homogeneous signal intensity drop diagnostic of lipid-rich adenoma 1, 2
• Both modalities receive an appropriateness rating of 8/9 from the American College of Radiology for indeterminate adrenal masses 1, 2

Important Limitations to Recognize

• Approximately 1/3 of pheochromocytomas may demonstrate washout characteristics mimicking adenomas, creating false negatives 1, 3
• Conversely, approximately 1/3 of adenomas do not washout in the typical adenoma range 1
• Malignant masses (including adrenocortical carcinoma and hypervascular metastases) can occasionally washout in the adenoma range 1, 2

Role of FDG-PET (Not Pentixafor)

If washout CT and chemical shift MRI remain inconclusive:

• FDG-PET should be considered before proceeding to biopsy, with SUV >4 typically indicating metastatic disease and <4 suggesting benign lesions 1
• FDG-PET demonstrates excellent sensitivity for metastases from lung, colon, melanoma, and lymphoma 1
• False-negative results occur with renal cell carcinoma metastases 1

What Gallium-68 Pentixafor Actually Does

Pentixafor is a highly specialized tracer that targets CXCR4 receptors:

• Pentixafor PET/CT is specifically designed for subtyping primary aldosteronism, distinguishing aldosterone-producing adenomas (APA) from idiopathic hyperaldosteronism (IHA) 4, 5, 6
• It demonstrates 90-93% sensitivity and 85-94% specificity for identifying functional aldosterone-producing nodules in patients with confirmed primary aldosteronism 4, 5, 6
• The tracer detects CXCR4 expression, which correlates with aldosterone synthase (CYP11B2) expression in functional nodules 4, 5
• Diagnostic accuracy is highest for nodules ≥1 cm (sensitivity up to 97.3%), though it shows promise even for micronodules <1 cm 4, 6

Critical Context

This imaging modality is only relevant after biochemical confirmation of primary aldosteronism (elevated aldosterone-to-renin ratio, suppressed renin) and is used to guide surgical decision-making in that specific population 7, 5, 6. It has no role in the general evaluation of indeterminate adrenal masses or in distinguishing benign adenomas from other pathology.

Practical Algorithm for Non-Conclusive CT

1. If initial non-contrast CT shows >10 HU: Proceed to washout CT or chemical shift MRI 1, 2
2. If washout CT/MRI remains indeterminate: Consider FDG-PET (particularly in patients with cancer history) 1
3. If all imaging inconclusive: Adrenal biopsy may be considered after excluding pheochromocytoma biochemically 1, 8
4. Alternative approach for small lesions (<4 cm): Follow-up imaging at 3-6 months to assess for growth 1, 8

Mandatory Biochemical Testing

• All patients require hormonal evaluation regardless of imaging characteristics, including screening for pheochromocytoma (plasma or 24-hour urinary metanephrines) before any invasive procedure 2, 8, 3
• Screening for subclinical Cushing syndrome and primary aldosteronism should be performed in all adrenal incidentalomas 1, 2