Nothing but NET: A Review of Norepinephrine Transporter Expression and Efficacy of I-131-mIBG Therapy

Neuroblastoma is unique amongst common pediatric cancers for its expression of the norepinephrine transporter (NET), enabling tumor-selective imaging and therapy with radioactive analogues of norepinephrine. The majority of neuroblastoma tumors are avid for I-123-metaiodobenzaguanidine (mIBG) on imaging, yet the therapeutic response to I-131-mIBG is only 30% in clinical trials, and off-target effects cause short- and long-term morbidity. We review the contemporary understanding of the tumor-selective uptake, retention, and efflux of meta-iodobenzylguanidine (mIBG) and strategies currently in development for improving its efficacy. Combination treatment strategies aimed at enhancing NET are likely necessary to reach the full potential of I-131-mIBG therapy. Pediatr Blood Cancer 2015;62:5-11 (c) 2014 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.