The Norepinephrine Transporter and Pheochromocytoma

Abstract:  Pheochromocytomas are rare neuroendocrine tumors of chromaffin cell origin that synthesize and secrete excess quantities of catecholamines and other vasoactive peptides. Pheochromocytomas also express the norepinephrine transporter (NET), a molecule that is used clinically as a means of incorporating radiolabelled substrates such as 131I‐MIBG (iodo‐metaiodobenzylguanidine) into pheochromocytoma tumor cells. This allows the diagnostic localization of these tumors and, more recently, 131I‐MIBG has been used in trials in the treatment of pheochromocytoma, potentially giving rise to NET as a therapeutic target. However, because of varying levels or activities of the transporter, the ability of 131I‐MIBG to be consistently incorporated into tumor cells is limited, and therefore various strategies to increase NET functional activity are being investigated, including the use of traditional chemotherapeutic agents such as cisplatin or doxorubicin. Other aspects of NET discussed in this short review include the regulation of the transporter and how novel protein–protein interactions between NET and structures such as syntaxin 1A may hold the key to innovative ways to increase the therapeutic value of 131I‐MIBG.