Abstract #2757
Acute changes in cellular-interstitial water exchange rate in DB-1 Melanoma xenografts after lonidamine administration as a marker of tumor energetics and ion transport
Kavindra Nath 1 , Ramesh Paudyal 2 , David S Nelson 1 , Stephen Pickup 1 , Rong Zhou 1 , Dennis B Leeper 3 , Daniel F Heitjan 1 , Charles S Springer 4 , Harish Poptani 1 , and Jerry D Glickson 1
1
University of Pennsylvania, Philadelphia,
Pennsylvania, United States,
2
Emory
University, Atlanta, Georgia, United States,
3
Thomas
Jefferson University, Philadelphia, Pennsylvania, United
States,
4
Advanced
Imaging Research Center, Oregon Health & Science
University, Portland, Oregon, United States
The aim of the current study was to evaluate whether the
changes in ATP levels after lonidamine (LND)
administration in DB-1 melanoma xenografts correlated
with changes in tumor i, a measure of mean lifetime of
intracellular water protons using the Shutter Speed
Model (SSM) in addition to Ktrans and ve. LND is a small
molecule that inhibits the monocarboxylate transporter-1
(MCT-1) that reduces tumor pH and bioenergetics. We
observed a significant decrease in Ktrans but increase
in i following LND administration, which is associated
with a change in cell size and membrane permeability or
ion transport. Changes in Ktrans and i might serve as
surrogate biomarkers, indicating that DCE-MRI not only
measures tissue vascular hemodynamics, but also the
transport activity and transmembrane water exchange or
cycling.
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