Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging.
Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecular imaging. CLT1-dL-(Gd-DOTA)4 was synthesized by conjugating four Gd-DOTA monoamide chelates to a CLT1 peptide via generation 1 lysine dendrimer. The T1 relaxivity of CLT1-dL-(Gd-DOTA)4 was 40.4 mM-1 s-1 per molecule (10.1 mM-1 s-1 per Gd) at 37 °C and 1.5 T. Fluorescence imaging showed high binding specificity of CLT1 to orthotopic PC3 prostate tumor in mice. The contrast agent resulted in improved tumor contrast enhancement in male athymic nude mice bearing orthotopic PC3 prostate tumor xenograft at a dose of 0.03 mmol Gd/kg. The peptide targeted MRI contrast agent is promising for high-resolution MR molecular imaging of prostate tumor.
Written by:
Wu X, Burden-Gulley SM, Yu GP, Tan M, Lindner D, Brady-Kalnay SM, Lu ZR. Are you the author?
Department of Biomedical Engineering, and ‡Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, United States.
Reference: Bioconjug Chem. 2012 Aug 15;23(8):1548-56.
doi: 10.1021/bc300009t
PubMed Abstract
PMID: 22812444
UroToday.com Investigative Urology Section
