ABSTRACT
The development of chemical exchange saturation transfer (CEST)
imaging agents in the Laboratory of Cardiac Energetics began
with our interest in the creatine kinase reaction kinetics in
vivo using 31P nuclear magnetic resonance (NMR) to monitor
the exchange between creatine phosphate (CrP) and the γP of
adenosine triphosphate (ATP). We had been examining the reaction
kinetics of this system in different tissues but were concerned
that the summing of the reaction kinetics over the large voxel of
the classical spectroscopy methods might be averaging different
rates across the tissues. Paul Hsieh was a Howard Hughes Medical
Institute-NIH Research Scholar who had done an excellent job of
characterizing the gross tissue exchange rate [1], and we decided
that the 25 mM CrP signal was sufficiently large that we might
be able to image the kinetics of the creatine kinase reaction by
monitoring the effect of saturating the lower concentration γP-ATP
and reading this out on the amplitude of CrP. We had previously
established that the saturation transfer process is a great way to
amplify the signal from low concentration exchange partners and
is even capable of observing enzyme substrate complexes. This
was recently reviewed by Alan Koretsky and Robert Balaban [2].
Important in this experiment was a control irradiation on the equal
but opposite side of the CrP resonance to control for imperfections
in the irradiation. The importance of this will become clear in the
following paragraphs. Paul was very successful in this effort. We
believe publishing the first image of a chemical exchange process
in living tissue [3]. Unfortunately, this paper was published in the
Journal of Magnetic Resonance, one of the best basic journals in the NMR field, in 1987 before it was covered in Pub Med and is thus not
easy to find by the biological and medical community.
