Maximizing T2-exchange in Dy(3+)DOTA-(amide)X chelates: fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI

Magn Reson Med. 2014 Mar;71(3):1179-85. doi: 10.1002/mrm.25091.


Purpose: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Chelating Agents
  • Contrast Media* / chemical synthesis
  • Dysprosium* / chemistry
  • Heterocyclic Compounds, 1-Ring* / chemistry
  • Magnetic Resonance Imaging / instrumentation
  • Magnetic Resonance Imaging / methods*
  • Phantoms, Imaging
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Water / chemistry*


  • Amides
  • Chelating Agents
  • Contrast Media
  • Heterocyclic Compounds, 1-Ring
  • Water
  • Dysprosium
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid