title: A biomarker-responsive T2exMRI contrast agent.
abstract: This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T2exchange (T2ex) properties after interacting with a molecular biomarker.
  
  
  
  The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O2. The R1and R2relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r2exrelaxivities.
  
  
  
  The reaction of Tm-DO3A-oAA with NO and O2caused a 6.4-fold increase in the r2relaxivity of the agent, whereas r1relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T2exagent. The effects of pH and temperature on the r2relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand.
  
  
  
  T2exMRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665-1670, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona.
authors.forename: Iman
authors.initials: I
authors.lastname: Daryaei
authors.affiliation: Department of Medical Imaging, University of Arizona.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Randtke
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona.|Department of Medical Imaging, University of Arizona.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pagel
mesh_terms: D000813:Anilides / Q000737:chemistry; D003287:Contrast Media / Q000032:analysis / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000032:analysis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000737:chemistry; D009569:Nitric Oxide / Q000032:analysis / Q000737:chemistry*; D010100:Oxygen / Q000032:analysis / Q000737:chemistry*; D013667:Technetium; D017556:Technetium Compounds / Q000737:chemistry*; D013696:Temperature
chemical_list: C520644:1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; D000813:Anilides; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D015335:Molecular Probes; D017556:Technetium Compounds; D009569:Nitric Oxide; D013667:Technetium; D010100:Oxygen
keywords: T2ex MRI; chemical exchange: molecular imaging; nitric oxide; responsive agent