title: Potential of N-acetylated-para-aminosalicylic acid to accelerate manganese enhancement decline for long-term MEMRI in rodent brain.
abstract: BACKGROUND
  Manganese (Mn(2+))-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn(2+) is relatively long with a half-life (t1/2) of 51-74 days causing a slow decline of MRI signal enhancement following Mn(2+) administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn(2+) from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn(2+) enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests.
  
  
  METHODS
  We investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn(2+), could affect the decline of Mn(2+) induced MRI enhancement in brain.
  
  
  CONCLUSIONS
  Two-week treatment with AcPAS (200mg/kg/dose×3 daily) accelerated the decline of Mn(2+) induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals.
  
  
  METHODS
  To the best of our knowledge, no method exists to accelerate the decline of the Mn(2+) induced MRI enhancement for repeated MEMRI tests.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States.
authors.forename: Aditya N
authors.initials: AN
authors.lastname: Bade
authors.affiliation: Department of Anesthesiology, Tongji Medical College, Huanzhong University of Science and Technology, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States.
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, United States.
authors.forename: Prabagaran
authors.initials: P
authors.lastname: Narayanasamy
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States.
authors.forename: Ram
authors.initials: R
authors.lastname: Veerubhotla
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States; Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5800, United States; Department of Radiology, University of Nebraska Medical Center, Omaha, NE, 68198-1045, United States. Electronic address: yutongliu@unmc.edu.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000636:Aminosalicylic Acids / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D002712:Chlorides / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: D000636:Aminosalicylic Acids; D002712:Chlorides; D017895:Manganese Compounds; C086759:acetyl 4-aminosalicylic acid; C025340:manganese chloride
keywords: Chelation; Manganese enhanced MRI (MEMRI); N-acetylated-para-aminosalicylic acid (AcPAS); Repeated MEMRI