title: Synthesis and evaluation of a targeted nanoglobular dual-modal imaging agent for MR imaging and image-guided surgery of prostate cancer.
abstract: OBJECTIVE
  To synthesize and evaluate a peptide targeted nanoglobular dual modal imaging agent specific to a cancer biomarker in tumor stroma for MRI and fluorescence visualization of prostate tumor in image-guided surgery.
  
  
  METHODS
  A peptide (CGLIIQKNEC, CLT1) targeted generation 2 nanoglobular (polylysine dendrimer with a silsesquioxane core) dual modal imaging agent, CLT1-G2-(Gd-DOTA-MA)-Cy5, was synthesized by stepwise conjugation of Gd-DOTA-MA, Cy5 and peptide to the dendrimer. Contrast enhanced MR imaging of the targeted dual imaging agent was evaluated on a Bruker 7T animal scanner with male athymic nude mice bearing orthotopic PC3-GFP prostate tumor. Fluorescence tumor imaging of the agent was carried out on a Maestro fluorescence imaging system.
  
  
  RESULTS
  The targeted agent CLT1-G2-(Gd-DOTA-MA)-Cy5 produced greater contrast enhancement in the tumor tissue than the control agent KAREC-G2-(Gd-DOTA-MA)-Cy5 at a dose of 30 μmol-Gd/kg in the MR images of the tumor bearing mice. Signal-to-noise ratio (SNR) of CLT1-G2-(Gd-DOTA-MA)-Cy5 in the tumor tissue was approximately 2 fold of that of the control agent in the first 15 min post-injection. The targeted agent also resulted in bright fluorescence signals in the tumor tissue.
  
  
  CONCLUSIONS
  The CLT1 peptide targeted nanoglobular dual-imaging agent CLT1-G2-(Gd-DOTA-MA)-Cy5 has a potential for MRI and fluorescence visualization of prostate tumor.
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: Zhen
authors.initials: Z
authors.lastname: Ye
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindner
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
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 / Q000138:chemical synthesis / Q000737:chemistry*; D005453:Fluorescence; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology / Q000601:surgery*; D025321:Surgery, Computer-Assisted / Q000295:instrumentation*
chemical_list: D002232:Carbocyanines; D003287:Contrast Media; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C085321:cyanine dye 5; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate