Molecular imaging of norepinephrine transporter-expressing tumors: current status and future prospects

Abstract

The human norepinephrine transporter (hNET) is a transmembrane protein responsible for reuptake of norepinephrine in presynaptic sympathetic nerve terminals and adrenal chromaffin cells. Neural crest tumors, such as neuroblastoma, paraganglioma and pheochromocytoma often show high hNET expression. Molecular imaging of these tumors can be done using radiolabeled norepinephrine analogs that target hNET. Currently, the most commonly used radiopharmaceutical for hNET imaging is meta-[ 123 I]iodobenzylguanidine ([ 123 I]MIBG) and this has been the case since its development several decades ago. The γ-emitter, iodine-123 only allows for planar scintigraphy and SPECT imaging. These modalities typically have a poorer spatial resolution and lower sensitivity than PET. Additional practical disadvantages include the fact that a two-day imaging protocol is required and the need for thyroid blockade. Therefore, several PET alternatives for hNET imaging are actively being explored. This review gives an in-depth overview of the current status and recent developments in clinical trials leading to the next generation of clinical PET ligands for imaging of hNET-expressing tumors.

Tailored Molecular Imaging of Pheochromocytoma and Paraganglioma: Which Tracer and When

“…MIBG is a substrate for the NE transporter and concentrates within intracellular storage granules via vesicular monoamine transporter (VMAT) 1 and VMAT2 of cells of neuroectodermal origin, such as those of adrenal or extra-adrenal PPGLs. Moreover, since 1983, 123 I-MIBG has been used apart from its diagnostic utility, in the form of 131 I-MIBG, for therapeutic purposes in chromaffin tumors and NETs [33]. In cases of adrenal PCCs, 123 I-MIBG scintigraphy shows high sensitivity and specificity values, of 90% and 95%, respectively, which increase to approximately 100% when combined with catecholamine measurements [34].…”

Nuclear medicine in precision oncology: a foreword

“…as we know from the somatostatin receptor imaging field, PET imaging is clinically superior to gamma-camera imaging 6 and this has led to widespread adoption of 68 ga-doTa-somatostatin analogues. 7 Pauwels et al 8 review in detail the molecular mechanisms behind hNeT imaging, the available radiopharmaceuticals with an emphasis on recently developed PeT tracers which outperform [ 123 i] MiBg and that might restore the pre-eminence of hNeT imaging in the management of neural crest tumors.…”