title: Radiosynthesis and evaluation of two novel 123I-labeled 2-methyl-4-nitroimidazole derivatives as potential infection imaging agents.
abstract: BACKGROUND
  The inflammation- and infection-seeking properties of (131)I-labeled ornidazole, a 5-nitroimidazole derivative, have recently been reported. Whole-body images in rabbits showed a more rapid uptake in inflamed areas compared to (67)Ga. In the present study, two novel (123)I-labeled 2-methyl-4-nitroimidazole derivatives were synthesized and their infection-seeking properties compared with those of (67)Ga and (123)I-labeled ornidazole.
  
  
  METHODS
  Radiolabeling was carried out by means of iodide-for-tosylate, triflate or halogen exchange. Various methods were utilized in order to synthesize the labeling precursors for the (123)I-labeled novel compounds. Serum stability studies on all of the (123)I-labeled tracers were followed by gamma camera imaging studies on rabbits artificially infected with Escherichia coli bacteria.
  
  
  CONCLUSIONS
  The (123)I-labeled tracers were obtained in moderate to good radiochemical yields (34-80%) and acceptable radiochemical purities (93-99%). In contrast to (123)I-labeled ornidazole, 1-[(1-hydroxy-3-[(123)I]iodoprop-2-yloxy)methyl]-2-methyl-4-nitroimidazole (2) and 1-[(1-[(123)I]iodoprop-2-yloxy)methyl]-2-methyl-4-nitroimidazole (3) showed high serum stability. Compared to noninfected controls, all of the (123)I-labeled tracers showed increased uptake at the area of induced infection after 6 and 24 h, but the uptake was significantly lower than in the case of (67)Ga over the same period. Tracer 3 showed a slightly superior uptake after 6 h than the other (123)I-labeled tracers over the same period. The advantage of the initially slightly faster rate at which nitroimidazole tracers appear to accumulate in the infection area in comparison to (67)Ga might not outweigh the advantage of the eventual higher target to nontarget ratio displayed by (67)Ga.
authors.affiliation: iThemba Laboratory for Accelerator-Based Sciences, PO Box 722, Somerset-West 7129, South Africa. niel@tlabs.ac.za
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Rossouw
authors.forename: Mattheus G
authors.initials: MG
authors.lastname: Lötter
authors.forename: Hanlie
authors.initials: H
authors.lastname: du Raan
authors.forename: Susara E
authors.initials: SE
authors.lastname: Jansen
authors.forename: Alexander
authors.initials: A
authors.lastname: Höhn
authors.forename: Ben V
authors.initials: BV
authors.lastname: Burger
mesh_terms: D000818:Animals; D002951:Citrates / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005708:Gallium / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009593:Nitroimidazoles / Q000737:chemistry / Q000493:pharmacokinetics; D009950:Ornidazole / Q000493:pharmacokinetics; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002951:Citrates; D007457:Iodine Radioisotopes; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C052586:2-methyl-5-nitroimidazole; D009950:Ornidazole; D005708:Gallium; C103850:gallium citrate