title: MR molecular imaging of prostate cancer with a peptide-targeted contrast agent in a mouse orthotopic prostate cancer model.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Wickenden Building, Room 427, 10900 Euclid Avenue, Cleveland, Ohio 44106-7207, USA.
authors.forename: Mingqian
authors.initials: M
authors.lastname: Tan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Burden-Gulley
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Xueming
authors.initials: X
authors.lastname: Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindner
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
authors.forename: Vikas
authors.initials: V
authors.lastname: Gulani
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D003287:Contrast Media; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles; D009942:Organometallic Compounds / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D002232:Carbocyanines; D003287:Contrast Media; D005353:Fibronectins; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D010456:Peptides, Cyclic; C085321:cyanine dye 5; C510872:cyclo(cysteinyl-glycyl-leucyl-isoleucyl-isoleucyl-glutaminyl-lysyl-asparaginyl-glutamyl-cysteinyl); D005337:Fibrin; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate