Norepinephrine Transporter As a Target for Imaging and Therapy

The norepinephrine transporter (NET) is essential for norepinephrine uptake at the synaptic terminals and adrenal chromaffin cells. In neuroendocrine tumors, NET can be targeted for imaging as well as therapy. One of the most widely used theranostic agents targeting NET is metaiodobenzylguanidine (MIBG), a guanethidine analog of norepinephrine. I/I-MIBG theranostics have been applied in the clinical evaluation and management of neuroendocrine tumors, especially in neuroblastoma, paraganglioma, and pheochromocytoma. I-MIBG imaging is a mainstay in the evaluation of neuroblastoma, and I-MIBG has been used for the treatment of relapsed high-risk neuroblastoma for several years, however, the outcome remains suboptimal. I-MIBG has essentially been only palliative in paraganglioma/pheochromocytoma patients. Various techniques of improving therapeutic outcomes, such as dosimetric estimations, high-dose therapies, multiple fractionated administration and combination therapy with radiation sensitizers, chemotherapy, and other radionuclide therapies, are being evaluated. PET tracers targeting NET appear promising and may be more convenient options for the imaging and assessment after treatment. Here, we present an overview of NET as a target for theranostics; review its current role in some neuroendocrine tumors, such as neuroblastoma, paraganglioma/pheochromocytoma, and carcinoids; and discuss approaches to improving targeting and theranostic outcomes.