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Maximizing T 2 ‐exchange in Dy 3+ DOTA‐(amide) X chelates: Fine‐tuning the water molecule exchange rate for enhanced T 2 contrast in MRI
Author(s) -
Soesbe Todd C.,
Ratnakar S. James,
Milne Mark,
Zhang Shanrong,
Do Quyen N.,
Kovacs Zoltan,
Sherry A. Dean
Publication year - 2014
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.25091
Subject(s) - chelation , chemistry , molecule , amide , dota , analytical chemistry (journal) , yield (engineering) , aqueous solution , reaction rate constant , nuclear magnetic resonance , kinetics , inorganic chemistry , materials science , organic chemistry , physics , metallurgy , quantum mechanics
Purpose The water molecule exchange rates in a series of DyDOTA‐(amide) X chelates were fine‐tuned to maximize the effects of T 2 ‐exchange line broadening and improve T 2 contrast. Methods Four DyDOTA‐(amide) X chelates having a variable number of glycinate side‐arms were prepared and characterized as T 2 ‐exchange agents. The nonexchanging DyTETA chelate was also used to measure the bulk water T 2 reduction due solely to T 2 *. The total transverse relaxivity (r 2tot ) at 22, 37, and 52°C for each chelate was measured in vitro at 9.4 Tesla (400 MHz) by fitting plots of total T 2 −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 (r 2ex ) and bound water lifetimes (τ M ) were in excellent agreement with Swift‐Connick theory, with DyDOTA‐(gly) 3 giving the largest r 2ex = 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 T 2 contrast agent for improved molecular imaging applications. Magn Reson Med 71:1179–1185, 2014. © 2014 Wiley Periodicals, Inc.