P-glycoprotein expression is associated with sestamibi washout in primary hyperparathyroidism

Abstract

Background: The detection of parathyroid adenomas by (99m)Tc-labelled hexakis 2-methoxyisobutyl isonitrile (sestamibi) scintigraphy is influenced by several factors, including tumour size and serum level of parathyroid hormone (PTH). This study examined the relationship between sestamibi accumulation and multidrug resistance (MDR)-related P-glycoprotein (P-gp) expression in a large series of surgically excised parathyroid tumours.

Methods: Seventy-eight patients underwent dual-phase sestamibi imaging before parathyroidectomy. Expression of P-gp within tumour cells was assessed by immunohistochemistry. Tumour size was measured and the ellipsoid volume calculated. Scan results were analysed in relation to preoperative serum levels of calcium and PTH, P-gp expression and tumour volume.

Results: Sixty-four of the 78 sestamibi scans were positive and 14 negative. Smaller adenomas (less than 0.5 cm(3)) were more likely to be sestamibi negative than larger lesions (P = 0.006). Ten of 14 adenomas with negative imaging showed strong P-gp membrane positivity and 45 of 64 lesions with a positive scan did not show P-gp membrane expression, indicating a significant association between high P-gp membrane immunoreactivity and negative sestamibi result (P = 0.006).

Conclusion: These data suggest an association between P-gp membrane expression and false-negative sestamibi scan result. Inhibition of the P-gp transmembrane pump using MDR modulators may therefore improve the sensitivity of sestamibi scintigraphy.