Imaging the norepinephrine transporter in neuroblastoma: A comparison of [18F]-MFBG and 123I-MIBG Journal Article

Authors: Zhang, H.; Huang, R.; Cheung, N. K. V.; Guo, H.; Zanzonico, P. B.; Thaler, H. T.; Lewis, J. S.; Blasberg, R. G.
Article Title: 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, 123I/131I-MIBG has several clinical limitations for diagnostic imaging. In the current studies, we evaluated meta-[18F]-fluorobenzylguanidine ([18F]-MFBG) and compared it with 123I-MIBG for imaging NET-expressing neuroblastomas. Experimental Design: NET expression levels in neuroblastoma cell lines were determined by Western blot and 123I-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 [18F]-MFBG in cells was specific and proportional to the expression level of NET. Although [18F]-MFBG had a 3-fold lower affinity for NET and an approximately 2-fold lower cell uptake in vitro compared with that of 123I-MIBG, the in vivo imaging and tissue radioactivity concentration measurements demonstrated higher [18F]-MFBG xenograft uptake and tumor-to-normal organ ratios at 1 and 4 hours after injection. A comparison of 4 hours [18F]-MFBG PET (positron emission tomography) imaging with 24 hours 123I-MIBG SPECT (single-photon emission computed tomography) imaging showed an approximately 3-fold higher tumor uptake of [18F]-MFBG, but slightly lower tumor-to-background ratios in mice. Conclusions: [18F]-MFBG is a promising radiopharmaceutical for specifically imaging NET-expressing neuroblastomas, with fast pharmacokinetics and whole-body clearance. [18F]-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 131I/123I-MIBG. © 2014 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 20
Issue: 8
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2014-04-15
Start Page: 2182
End Page: 2191
Language: English
DOI: 10.1158/1078-0432.ccr-13-1153
PROVIDER: scopus
PUBMED: 24573553
PMCID: PMC4072734
Notes: Clin. Cancer Res. -- Export Date: 2 June 2014 -- CODEN: CCREF -- Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    439 Cheung
  2. Ronald G Blasberg
    242 Blasberg
  3. Ruimin Huang
    29 Huang
  4. Pat B Zanzonico
    246 Zanzonico
  5. Hanwen Zhang
    29 Zhang
  6. Jason S Lewis
    243 Lewis
  7. Howard T Thaler
    191 Thaler
  8. Hong-Fen Guo
    36 Guo