Prostate Cancer Evaluation: Design, Synthesis, and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents
Abstract
The lacZ gene encoding E. coli beta-gal has already been recognized as the most commonly used reporter system in cancer gene therapy. Moreover, prostrate-specific membrane antigen (PSMA) has been identified as an ideal antigenic target in prostate cancer. We propose to develop a novel class of Gd(III)-based MRI contrast agents for in vivo detection of beta-gal or PSMA activity. This new concept of the GD(III)-based MRI contrast agents is composed of three moieties: (A) a signal enhancement group, such as Gd-DOTA or Gd-PCTA; (B) an Fe(III) chelating group; (C) beta-D-galactose or glutamate. Following cleavage by lacZ transgene or PSMA in prostate cancer cells, the released, activated aglycone Fe(III)-ligand will spontaneously trap endogenous Fe(III) at the site of enzyme activity forming a highly stable complex, to restrict motion of the GD(III) chelates enhancing relaxivity and providing local contrast accumulation. We plan to synthesize 8 novel MRI contrast agents for imaging beta-gal or PSMA activity in prostate cancer cell culture, explore the feasibility of applying the most promising analogies to cells grown in vivo in mice and rats.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA460803
Entities
People
- Jian-xin Yu
Organizations
- University of Texas at Dallas