Peptide-targeted Nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance cancer molecular imaging.
Effective imaging of a cancer molecular biomarker is critical for accurate cancer diagnosis and prognosis. CLT1 peptide was observed to specifically bind to the fibrin-fibronectin complexes presented in tumor extracellular matrix. In this study, we synthesized and evaluated CLT1 peptide-targeted nanoglobular Gd-DOTA monoamide conjugates for magnetic resonance (MR) imaging of the fibrin-fibronectin complexes in tumor. The targeted nanoglobular contrast agents were prepared by conjugating peptide CLT1 to G2 and G3 nanoglobule (lysine dendrimers with a cubic silsesquioxane core) Gd-DOTA monoamide conjugates via click chemistry. The T(1) relaxivities of peptide-targeted G2 and G3 nanoglobules were 7.92 and 8.20 mM(-1) s(-1) at 3T, respectively. Approximately 2 peptides and 25 Gd-DOTA chelates were conjugated onto the surface of 32 amine groups of G2 nanoglobule, and 3 peptides and 43 Gd-DOTA chelates onto the surface of 64 amine groups of G3 nanoglobule. The peptide-targeted nanoglobular contrast agents showed greater contrast enhancement than the corresponding nontargeted agents in tumor at a dose of 0.03 mmol-Gd/kg in female athymic mice bearing MDA-MB-231 human breast carcinoma xenografts. The targeted MRI contrast agents have a potential for specific cancer molecular imaging with MRI.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Mingqian
M
Tan
Xueming
X
Wu
Eun-Kee
EK
Jeong
Qianjin
Q
Chen
Zheng-Rong
ZR
Lu
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D049329:Nanostructures; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D010455:Peptides / Q000737:chemistry*; D014018:Tissue Distribution
D003287:Contrast Media; D005353:Fibronectins; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D010455:Peptides; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate