Imaging the Norepinephrine Transporter in Neuroblastoma: A Comparison of [F]-MFBG and I-MIBG

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, I/I-MIBG has several clinical limitations for diagnostic imaging. In the current studies, we evaluated meta-[F]-fluorobenzylguanidine ([F]-MFBG) and compared it with I-MIBG for imaging NET-expressing neuroblastomas. Experimental Design: NET expression levels in neuroblastoma cell lines were determined by Western blot and 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 [F]-MFBG in cells was specific and proportional to the expression level of NET. Although [F]-MFBG had a 3-fold lower affinity for NET and an approximately 2-fold lower cell uptake in vitro compared with that of I-MIBG, the in vivo imaging and tissue radioactivity concentration measurements demonstrated higher [F]-MFBG xenograft uptake and tumor-to-normal organ ratios at 1 and 4 hours after injection. A comparison of 4 hours [F]-MFBG PET (positron emission tomography) imaging with 24 hours I-MIBG SPECT (single-photon emission computed tomography) imaging showed an approximately 3-fold higher tumor uptake of [F]-MFBG, but slightly lower tumor-to-background ratios in