title: Maximizing T2-exchange in Dy(3+)DOTA-(amide)X chelates: fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI.
abstract: OBJECTIVE
  The water molecule exchange rates in a series of DyDOTA-(amide)X chelates were fine-tuned to maximize the effects of T2-exchange line broadening and improve T2 contrast.
  
  
  METHODS
  Four DyDOTA-(amide)X chelates having a variable number of glycinate side-arms were prepared and characterized as T2-exchange agents. The nonexchanging DyTETA chelate was also used to measure the bulk water T2 reduction due solely to T2*. The total transverse relaxivity (r2tot) at 22, 37, and 52°C for each chelate was measured in vitro at 9.4 Tesla (400 MHz) by fitting plots of total T2 (-1) versus concentration. The water molecule exchange rates for each complex were measured by fitting (17)O line-width versus temperature data taken at 9.4 Tesla (54.3 MHz).
  
  
  RESULTS
  The measured transverse relaxivities due to water molecule exchange (r2ex) and bound water lifetimes (τM) were in excellent agreement with Swift-Connick theory, with DyDOTA-(gly)3 giving the largest r2ex = 11.8 s(-1) mM(-1) at 37°C.
  
  
  CONCLUSIONS
  By fine-tuning the water molecule exchange rate at 37°C, the transverse relaxivity has been increased by 2 to 30 times compared with previously studied Dy(3+)-based chelates. Polymerization or dendrimerization of the optimal chelate could yield a highly sensitive, molecule-sized T2 contrast agent for improved molecular imaging applications.
authors.affiliation: Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, USA; Department of Radiology, UT Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Soesbe
authors.forename: S James
authors.initials: SJ
authors.lastname: Ratnakar
authors.forename: Mark
authors.initials: M
authors.lastname: Milne
authors.forename: Shanrong
authors.initials: S
authors.lastname: Zhang
authors.forename: Quyen N
authors.initials: QN
authors.lastname: Do
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
mesh_terms: D000577:Amides / Q000737:chemistry*; D002614:Chelating Agents; D003287:Contrast Media / Q000138:chemical synthesis; D004419:Dysprosium / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D019047:Phantoms, Imaging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014867:Water / Q000737:chemistry*
chemical_list: D000577:Amides; D002614:Chelating Agents; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D014867:Water; D004419:Dysprosium; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid