Nothing but NET: a review of norepinephrine transporter expression and efficacy of 131I-mIBG therapy

Pediatr Blood Cancer. 2015 Jan;62(1):5-11. doi: 10.1002/pbc.25200. Epub 2014 Aug 30.


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 (123)I-metaiodobenzaguanidine (mIBG) on imaging, yet the therapeutic response to (131) I-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 (131)I-mIBG therapy.

Keywords: meta-iodobenzylguanidine; neuroblastoma; norepinephrine transporter.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 3-Iodobenzylguanidine / therapeutic use*
  • Humans
  • Iodine Radioisotopes / therapeutic use*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Neuroblastoma / radiotherapy*
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism*
  • Prognosis
  • Radiopharmaceuticals / therapeutic use*


  • Iodine Radioisotopes
  • Norepinephrine Plasma Membrane Transport Proteins
  • Radiopharmaceuticals
  • 3-Iodobenzylguanidine