MR molecular imaging of prostate cancer with a peptide-targeted contrast agent in a mouse orthotopic prostate cancer model

Pharm Res. 2012 Apr;29(4):953-60. doi: 10.1007/s11095-011-0635-y. Epub 2011 Dec 3.

Abstract

Purpose: To study the effectiveness of a peptide targeted nanoglobular Gd-DOTA complexes for MR molecular imaging of prostate cancer in a mouse orthotopic PC-3 prostate cancer model.

Methods: A CLT1 (CGLIIQKNEC) peptide-targeted generation 2 nanoglobular Gd-DOTA monoamide conjugate [CLT1-G2-(Gd-DOTA)] was used for imaging fibrin-fibronectin complexes in prostate tumor using a non-specific peptide KAREC modified conjugate, KAREC-G2-(Gd-DOTA) as a control. Cy5 conjugates of CLT1 and KAREC were synthesized for binding studies. Orthotopic PC-3 prostate tumors were established in the prostate of athymic male nude mice. MRI study was performed on a Bruker 7T small animal MRI system.

Results: CLT1 peptide showed specific binding in the prostate tumor with no binding in normal tissues. The control peptide had little binding in normal and tumor tissues. CLT1-G2-(Gd-DOTA) resulted in stronger contrast enhancement in tumor tissue than KAREC-G2-(Gd-DOTA). CLT1-G2-(Gd-DOTA) generated ~100% increase in contrast-to-noise ratio (CNR) in the tumor compared to precontrast CNR at 1 min post-injection, while KAREC-G2-(Gd-DOTA) resulted in 8% increase.

Conclusion: CLT1-G2-(Gd-DOTA) is a promising molecular MRI contrast agent for fibrin-fibronectin complexes in tumor stroma. It has potential for diagnosis and assessing prognosis of malignant tumors with MRI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbocyanines* / chemistry
  • Cell Line, Tumor
  • Contrast Media*
  • Disease Models, Animal
  • Fibrin / metabolism
  • Fibronectins / metabolism
  • Fluorescent Dyes* / chemistry
  • Heterocyclic Compounds* / chemistry
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Nude
  • Molecular Imaging / methods*
  • Nanoparticles
  • Organometallic Compounds* / chemistry
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Transplantation, Heterologous

Substances

  • Carbocyanines
  • Contrast Media
  • Fibronectins
  • Fluorescent Dyes
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Peptides, Cyclic
  • cyanine dye 5
  • cyclo(cysteinyl-glycyl-leucyl-isoleucyl-isoleucyl-glutaminyl-lysyl-asparaginyl-glutamyl-cysteinyl)
  • Fibrin
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate