1. Imaging the Norepinephrine Transporter in Neuroblastoma: A Comparison of [18F]-MFBG and 123I-MIBG
- Author
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Nai-Kong V. Cheung, Hongfen Guo, Ruimin Huang, Jason S. Lewis, Hanwen Zhang, Pat Zanzonico, Ronald G. Blasberg, and Howard T. Thaler
- Subjects
Diagnostic Imaging ,Cancer Research ,Immunoblotting ,Transplantation, Heterologous ,Scintigraphy ,Guanidines ,Article ,Mice ,Neuroblastoma ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Tissue Distribution ,Catecholamine uptake ,Tomography, Emission-Computed, Single-Photon ,Norepinephrine Plasma Membrane Transport Proteins ,medicine.diagnostic_test ,biology ,business.industry ,Reproducibility of Results ,medicine.disease ,Immunohistochemistry ,Fluorobenzenes ,Transplantation ,3-Iodobenzylguanidine ,Oncology ,Norepinephrine transporter ,Positron emission tomography ,Positron-Emission Tomography ,biology.protein ,Cancer research ,Radiopharmaceuticals ,Nuclear medicine ,business ,Preclinical imaging - 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. Clin Cancer Res; 20(8); 2182–91. ©2014 AACR.
- Published
- 2014