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

Hanwen Zhang, Ruimin Huang, Nai Kong V. Cheung, Hongfen Guo, Pat B. Zanzonico, Howard T. Thaler, Jason S. Lewis, Ronald G. Blasberg

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish
Pages (from-to)2182-2191
Number of pages10
JournalClinical Cancer Research
Volume20
Issue number8
DOIs
StatePublished - Apr 15 2014
Externally publishedYes

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    Zhang, H., Huang, R., Cheung, N. K. V., Guo, H., Zanzonico, P. B., Thaler, H. T., Lewis, J. S., & Blasberg, R. G. (2014). Imaging the norepinephrine transporter in neuroblastoma: A comparison of [18F]-MFBG and 123I-MIBG. Clinical Cancer Research, 20(8), 2182-2191. https://doi.org/10.1158/1078-0432.CCR-13-1153