title: Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging.
abstract: The novel compound, (S)-amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic acid (BrVAIB, [(76)Br]5), was characterized against the known system A tracer, IVAIB ([(123)I]8). [(76)Br]5 was prepared in a 51% ± 19% radiochemical yield with high radiochemical purity (≥98%). The biological properties of [(76)Br]5 were compared with those of [(123)I]8. Results showed that [(76)Br]5 undergoes mixed amino acid transport by system A and system L transport, while [(123)I]8 had less uptake by system L. [(76)Br]5 demonstrated higher uptake than [(123)I]8 in DBT tumors 1 h after injection (3.7 ± 0.4% ID/g vs 1.5 ± 0.3% ID/g) and also showed higher uptake vs [(123)I]8 in normal brain. Small animal PET studies with [(76)Br]5 demonstrated good tumor visualization of intracranial DBTs up to 24 h with clearance from normal tissues. These results indicate that [(76)Br]5 is a promising PET tracer for brain tumor imaging and lead compound for a mixed system A and system L transport substrate.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bartels
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Aixiao
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Liya
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Keith
authors.initials: K
authors.lastname: Rich
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McConathy
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Lapi
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000586:Amination; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001967:Bromine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D003437:Crotonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D014018:Tissue Distribution
chemical_list: C527731:2-amino-2-methyl-4-iodo-3-butenoic acid; D001967:Bromine Radioisotopes; D003437:Crotonates; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C108891:3-bromosenecioic acid; D000409:Alanine