title: Development of intravascular contrast agents for MRI using gadolinium chelates.
abstract: Two MRI contrast agents (CAs) composed of Gd-DO3A conjugated to amino acid building blocks derived from glutamic acid (CA1) and lysine (CA2) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. In vitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2 mM. The longitudinal relaxivities (r(1) ) of CA1 and CA2 measured at 9.4 T are 6.4 and 5.4 mM(-1)  s(-1) in H(2) O at 25 °C, respectively. Both r(1) values are higher than those of CAs in clinical use: Gd-DTPA (Magnevist, Bayer Schering, Germany) and Gd-DOTA (Dotarem, Guerbet, France). In vivo imaging in Wistar rats demonstrated considerable signal enhancement (∼50 %) in the brain artery by CA2, but lower signal enhancement (∼30 %) by CA1. In contrast to Dotarem, which showed a similar signal enhancement as CA2, the enhancement by CA2 remained high (∼30 %), even at 52 min post-injection. This demonstrates that CA2 has a much longer blood half-life (68.1 min), which could be advantageous for angiography and tissue targeting.
authors: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors: Krisada
authors: K
authors: Kittigowittana
authors: Chang-Tong
authors: CT
authors: Yang
authors: Wai Ching
authors: WC
authors: Cheah
authors: Kai-Hsiang
authors: KH
authors: Chuang
authors: Chew-Yuan
authors: CY
authors: Tuang
authors: Young-Tae
authors: YT
authors: Chang
authors: Xavier
authors: X
authors: Golay
authors: Roderick W
authors: RW
authors: Bates
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D056831:Coordination Complexes; D009942:Organometallic Compounds; D018698:Glutamic Acid; D005682:Gadolinium; D008239:Lysine