title: Imaging the norepinephrine transporter in neuroblastoma: a comparison of [18F]-MFBG and 123I-MIBG.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Authors' Affiliations: Departments of Radiology, Pediatrics, Neurology, Medical Physics, Epidemiology and Biostatistics, and Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Ruimin
authors.initials: R
authors.lastname: Huang
authors.forename: Nai-Kong V
authors.initials: NK
authors.lastname: Cheung
authors.forename: Hongfen
authors.initials: H
authors.lastname: Guo
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Howard T
authors.initials: HT
authors.lastname: Thaler
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Blasberg
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D005464:Fluorobenzenes / Q000493:pharmacokinetics; D006146:Guanidines / Q000493:pharmacokinetics; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: C107924:3-fluorobenzylguanidine; D005464:Fluorobenzenes; D006146:Guanidines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; C493227:SLC6A2 protein, human; D019797:3-Iodobenzylguanidine