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

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.

• Authors: Mingqian Tan, Susan M Burden-Gulley, Wen Li, Xueming Wu, Daniel Lindner, Susann M Brady-Kalnay, Vikas Gulani, Zheng-Rong Lu
• Journal: Pharmaceutical research (Pharm Res) Vol. 29 Issue 4 Pg. 953-60 (Apr 2012) ISSN: 1573-904X [Electronic] United States
• PMID: 22139536 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, metabolism)
• Prostatic Neoplasms (diagnosis, metabolism, pathology)
• Transplantation, Heterologous