Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI
Technical Report,01 Feb 2014,31 Jan 2015
University of Texas Southwestern Medical Center at Dallas Dallas
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Purpose To develop a targeted T2-exchange MRI contrast agent for the early detection and diagnosis of prostate cancer. Scope This contrast agent is based on T2 contrast i.e., hypo-intense contrast arising from water molecule exchange between the inner-sphere of a Dysprosium Dy3 central ion and the bulk water. The level of this T2-exchange contrast is highly dependent on both the water molecule exchange rate and the paramagnetic shift of the water molecule hydrogen protons when bound to the Dy3 ion. After identifying which DyDOTA-based chelate gave the optimal water molecule exchange rate at 9.4 T MRI, the chelate would then be polymerized to increase the transverse relaxivity r2 per molecule by 100 fold. Thereby creating a highly sensitive, low molecular weight T2 contrast agent for cancer molecular imaging with MRI. Polymers targeting the prostate specific membrane antigen PSMA of prostate cancer cells would then be synthesized and tested with both in vitro and in vivo experiments. Major Findings We found that the DyDOTA-gly2 and DyDOTA-gly3 chelates had almost ideal water molecule exchange rates at 9.4 T and 37 degrees Celsius, which gave them transverse relaxivities r2 that were close to the theoretical maximum predicted by Swift-Connick theory. These two chelates were then chosen as candidates for polymerization. We also found that the paramagnetic shift in the bound water molecule hydrogen protons for each DyDOTA-based chelate was dependent on temperature. Details of these experiments and results are given in our Magnetic Resonance in Medicine publication. Unfortunately, polymerization of the DyDOTA-gly2 and DyDOTA-gly3 chelates proved to be extremely difficult, and only oneversion of the monomer chelates DyDOTA was successfully polymerized before the grant period ended. An alternate faster method could be to use dendrimers n16,32,64 instead of polymers to increase the total transverse relaxivity r2 per molecule.
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