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Magnetic‐Field‐Dependent 1 H Relaxivity Behavior of Biotin/Avidin‐Based Magnetic Resonance Imaging Probes
Author(s) -
Dhingra Verma Kirti,
Mishra Anurag,
Engelmann Jörn,
Beyerlein Michael,
Maier Martin E.,
Logothetis Nikos K.
Publication year - 2012
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.201200064
Subject(s) - avidin , nuclear magnetic resonance , gadolinium , chemistry , magnetic resonance imaging , biotin , in vivo , biochemistry , physics , medicine , microbiology and biotechnology , organic chemistry , biology , radiology
One major challenge in noninvasive mapping of various molecular targets is their inherently low in vivo concentration coupled with the insensitivity of imaging modalities, such as the widely used magnetic resonance imaging (MRI). Development of agents with high sensitivity and specificity is of paramount importance for structural and functional noninvasive imaging. The design, synthesis, and physiochemical characterization of two gadolinium‐based contrast agents (CAs) for MRI, the sensitivity of which was optimized by exploiting the well‐established biotin–avidin amplification strategies, are reported. The relaxivity of these agents showed a large increase if bound to avidin; specifically, the first compound showed an approximately 1000 % increase in transverse proton relaxivity ( r 2p ), whereas the second compound had an approximately 250 % r 2p increase. The increase in r 2p was magnetic field independent in the range of 1.5–16.4 T whereas the longitudinal proton relaxivity ( r 1p ) showed strong field dependence. The CAs were further characterized by measuring luminescence lifetimes and emission spectral changes upon addition of avidin to their Eu 3+ analogues. The difference in relaxation rate behavior of both complexes was explained on the basis of hydration number modulation and the “global/internal motion concept”. The association constant of these CAs with avidin was found to be in the range of approximately 10 15 M −1 , which shows that the coupling of biotin to Gd‐DO3A did not affect its affinity for binding to avidin (DO3A=1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid).