Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI
Abstract
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-(gly)2 and DyDOTA-(gly)3 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-(gly)2 and DyDOTA-(gly)3 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 (n=16,32,64) instead of polymers to increase the total transverse relaxivity (r2) per molecule.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2015
- Accession Number
- AD1036001
Entities
People
- A. D. Sherry
- James Ratnaker
- Lei Zhang
- Mark Milne
- Todd C. Soesbe
- Yunkou Wu
Organizations
- University of Texas Southwestern Medical Center