The effect of dexamethasone on tissue water distribution and proton relaxation in Panc02 tumors

The present experiments were conducted to determine the effects of dexamethasone mediated changes in tumor water distribution on proton relaxation times (T1, T2) in a murine pancreatic adenocarcinoma (Panc02). Spin lattice (T1) and spin-spin(T2) relaxation times were determined by ex vivo methods (10 MHz) and by in vivo imaging techniques (6.25 MHz) at various intervals after single or multiple dexamethasone treatments. In complementary studies, dexamethasone mediated changes in tumor capillary permeability, tumor water distribution, relative tumor blood flow and tumor cell proliferation were also determined. Proton spin lattice (T1) and spin-spin (T2 relaxation times for Panc02 tumors shortened within two hours of a single dexamethasone treatment. The time course and magnitude of this response was dexamethasone dose dependent. The time dependent changes in T1 and T2 after dexamethasone were similar at 10 MHz (ex vivo) and 6.25 MHz (in vivo imaging). Although dexamethasone produced little or no change in total tumor water content and tumor cell proliferation, transient changes in the physiologic distribution of tumor water were clearly demonstrated. The data supports the idea that dexamethasone induced changes in the distribution of tumor water were mediated by changes in capillary permeability and tumor blood flow. These physiologic responses produced serial changes in tumor extracellular extravascular water content that were consistent with the observed changes in tumor T1 and T2. The results from these experiments might imply that therapy associated changes in tumor proton relaxation times may not only reflect changes in tissue water content, but may also reflect physiologic responses which alter the distribution of tissue water and solute.