title: No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation.
abstract: Iodine-131-metaiodobenzylguanidine ([131I]MIBG) is a radiopharmaceutical for imaging as well as targeted radiotherapy of neuroblastoma. It is predicted that the use of no-carrier-added [131I]MIBG, rather than the conventional low specific activity preparation, will result in an enhanced therapeutic ratio because of different transport processes in neuroblastoma compared with most normal tissues.
  
  
  METHODS
  The main aims of the study were: (1) to determine whether [131I]MIBG of substantially greater specific activity is transported into tumor cells by the same process as the existing compound; (2) to evaluate the effect of nonradiolabeled MIBG on the cytotoxicity of no-carrier-added [131I]MIBG; and (3) to compare the biodistribution of both preparations of the radiochemical in neuroblastoma xenografts.
  
  
  RESULTS
  Active uptake of no-carrier-added [131I]MIBG was temperature-, sodium- and oxygen-dependent; ouabain- and desmethylimipramine-inhibitable; and could be blocked competitively by monoamine inhibitors of the noradrenaline transport mechanism. The rank order of specific uptake capacity in a panel of neuroblastoma cell lines was the same for both low and high specific activity drug. Neuroblastoma spheroid regrowth was 85% inhibited by no-carrier-added [131I]MIBG at 2 MBq.ml-1. Inhibitory potency was reduced in a dose-dependent manner by nonradiolabeled MIBG. The accumulation of no-carrier-added [131I]MIBG was significantly greater in tumor, adrenal, heart and skin of tumor-bearing mice than that of the conventional therapy preparation of [131I]MIBG.
  
  
  CONCLUSIONS
  These data indicate that there may be clinical advantages in the use of no-carrier-added [131I]MIBG rather than conventional [131I]MIBG.
authors.affiliation: Department of Radiation Oncology, University of Glasgow, Beatson Laboratory, Scotland.
authors.forename: R J
authors.initials: RJ
authors.lastname: Mairs
authors.forename: S H
authors.initials: SH
authors.lastname: Cunningham
authors.forename: J
authors.initials: J
authors.lastname: Russell
authors.forename: A
authors.initials: A
authors.lastname: Armour
authors.forename: J
authors.initials: J
authors.lastname: Owens
authors.forename: K
authors.initials: K
authors.lastname: McKellar
authors.forename: M N
authors.initials: MN
authors.lastname: Gaze
mesh_terms: D019797:3-Iodobenzylguanidine; D000818:Animals; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007462:Iodobenzenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000378:metabolism / Q000532:radiotherapy; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D014407:Tumor Cells, Cultured
chemical_list: D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine