Maximizing T2-exchange in Dy3+DOTA-(amide) X chelates: Fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI

Todd C. Soesbe, S. James Ratnakar, Mark Milne, Shanrong Zhang, Quyen N. Do, Zoltan Kovacs, A. Dean Sherry

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Abstract

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 17O 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 Dy3+-based chelates. Polymerization or dendrimerization of the optimal chelate could yield a highly sensitive, molecule-sized T2 contrast agent for improved molecular imaging applications.

Original languageEnglish (US)
Pages (from-to)1179-1185
Number of pages7
JournalMagnetic Resonance in Medicine
Volume71
Issue number3
DOIs
Publication statusPublished - Mar 2014

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Keywords

  • Dysprosium(III)
  • in vitro
  • MRI
  • T contrast
  • T-exchange
  • water molecule exchange

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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