title: Chlorotoxin-modified macromolecular contrast agent for MRI tumor diagnosis.
abstract: Clinical diagnosis of cancers using magnetic resonance imaging (MRI) is highly dependent on contrast agents, especially for brain tumors which contain blood-brain barrier (BBB) at the early stage. However, currently mostly used low molecular weight contrast agents such as Gd-DTPA suffer from rapid renal clearance, non-specificity, and low contrast efficiency. The aim of this paper is to investigate the potential of a macromolecular MRI contrast agent based on dendrigraft poly-l-lysines (DGLs), using chlorotoxin (CTX) as a tumor-specific ligand. The contrast agent using CTX-modified conjugate as the main scaffold and Gd-DTPA as the payload was successfully synthesized. The results of fluorescent microscopy showed that the modification of CTX could markedly enhance the cellular uptake in C6 glioma and liver tumor cell lines, but not in normal cell line. Significantly increased accumulation of CTX-modified conjugate within glioma and liver tumor was further demonstrated in tumor-bearing nude mice using in vivo imaging system. The MRI results showed that the signal enhancement of mice treated with CTX-modified contrast reached peak level at 5 min for both glioma and liver tumor, 144.97% ± 19.54% and 158.69% ± 12.41%, respectively, significantly higher than that of unmodified counterpart and commercial control. And most importantly, the signal enhancement of CTX-modified contrast agent maintained much longer compared to that of controls, which might be useful for more exact diagnosis for tumors. CTX-modified dendrimer-based conjugate might be applied as an efficient MRI contrast agent for targeted and accurate tumor diagnosis. This finding is especially important for tumors such as brain glioma which is known hard to be diagnosed due to the presence of BBB.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Rongqin
authors.initials: R
authors.lastname: Huang
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Shao
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Kuang
authors.forename: Xing
authors.initials: X
authors.lastname: Hu
authors.forename: Xuxia
authors.initials: X
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Lei
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D012604:Scorpion Venoms; C091539:Chlorotoxin; D011107:Polylysine