Prostate Cancer Evaluation: Design, Synthesis and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents
Final rept. 15 Sep 2005-14 Sep 2010
TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
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The lacZ gene encoding E. coli beta-gal has already been recognized as the most commonly used reporter system in cancer gene therapy. Moreover, prostate-specific membrane antigen PSMA has been identified as an ideal antigenic target in prostate cancer. We propose to develop a novel class of GdIII-based MRI contrast agents for in vivo detection of beta-gal or PSMA activity. This new concept of the GdIII-based MRI contrast agents is composed of three moieties A a signal enhancement group, such as Gd-DOTA or Gd-PCTA B an FeIII chelating group C beta-D-galactose or glutamate. Following cleavage by lacZ transgene or PSMA in prostate cancer cells, the released, activated aglycone FeIII-ligand will spontaneously trap endogenous FeIII at the site of enzyme activity forming a highly stable complex, to restrict motion of the GdIII chelates enhancing relaxivity and providing local contrast accumulation. We plan to synthesize 8 novel MRI contrast agnets 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.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research