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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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