Imaging the norepinephrine transporter in neuroblastoma: a comparison of [18F]-MFBG and 123I-MIBG.

Abstract

PURPOSE:

The norepinephrine transporter (NET) is a critical regulator of catecholamine uptake in normal physiology and is expressed in neuroendocrine tumors like neuroblastoma. Although the norepinephrine analog, meta-iodobenzylguanidine (MIBG), is an established substrate for NET, (123)I/(131)I-MIBG has several clinical limitations for diagnostic imaging. In the current studies, we evaluated meta-[(18)F]-fluorobenzylguanidine ([(18)F]-MFBG) and compared it with (123)I-MIBG for imaging NET-expressing neuroblastomas.

EXPERIMENTAL DESIGN:

NET expression levels in neuroblastoma cell lines were determined by Western blot and (123)I-MIBG uptake assays. Five neuroblastoma cell lines and two xenografts (SK-N-BE(2)C and LAN1) expressing different levels of NET were used for comparative in vitro and in vivo uptake studies.

RESULTS:

The uptake of [(18)F]-MFBG in cells was specific and proportional to the expression level of NET. Although [(18)F]-MFBG had a 3-fold lower affinity for NET and an approximately 2-fold lower cell uptake in vitro compared with that of (123)I-MIBG, the in vivo imaging and tissue radioactivity concentration measurements demonstrated higher [(18)F]-MFBG xenograft uptake and tumor-to-normal organ ratios at 1 and 4 hours after injection. A comparison of 4 hours [(18)F]-MFBG PET (positron emission tomography) imaging with 24 hours (123)I-MIBG SPECT (single-photon emission computed tomography) imaging showed an approximately 3-fold higher tumor uptake of [(18)F]-MFBG, but slightly lower tumor-to-background ratios in mice.

CONCLUSIONS:

[(18)F]-MFBG is a promising radiopharmaceutical for specifically imaging NET-expressing neuroblastomas, with fast pharmacokinetics and whole-body clearance. [(18)F]-MFBG PET imaging shows higher sensitivity, better detection of small lesions with low NET expression, allows same day scintigraphy with a shorter image acquisition time, and has the potential for lower patient radiation exposure compared with (131)I/(123)I-MIBG.

• Authors: Hanwen Zhang, Ruimin Huang, Nai-Kong V Cheung, Hongfen Guo, Pat B Zanzonico, Howard T Thaler, Jason S Lewis, Ronald G Blasberg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 8 Pg. 2182-91 (Apr 15 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24573553 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2014 AACR.

Chemical References

• 3-fluorobenzylguanidine
• Fluorobenzenes
• Guanidines
• Norepinephrine Plasma Membrane Transport Proteins
• Radiopharmaceuticals
• SLC6A2 protein, human
• 3-Iodobenzylguanidine

Topics

• 3-Iodobenzylguanidine (pharmacokinetics)
• Animals
• Cell Line, Tumor
• Diagnostic Imaging (methods)
• Fluorobenzenes (pharmacokinetics)
• Guanidines (pharmacokinetics)
• Humans
• Immunoblotting
• Immunohistochemistry
• Mice
• Neuroblastoma (diagnostic imaging, metabolism, pathology)
• Norepinephrine Plasma Membrane Transport Proteins (metabolism)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (pharmacokinetics)
• Reproducibility of Results
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)
• Transplantation, Heterologous