title: An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography.
abstract: An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2″-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3 T, 7 T and 9.4 T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. In vitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2 mM [Gd] concentration. In vivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2 mM [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0 mM [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0 mM [Gd]). The DO3A-Lys has been labeled with (68)Ga radioisotope for biodistribution studies. (68)Ga(DO3A-Lys) has high uptake in both HT1080 and U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and displays promising characteristics of an MRI contrast agent for tumor angiography.
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, #02-02 Helios, Singapore 138667, Singapore. Electronic address: yang_changtong@sbic.a-star.edu.sg.
authors.forename: Chang-Tong
authors.initials: CT
authors.lastname: Yang
authors.forename: Prashant
authors.initials: P
authors.lastname: Chandrasekharan
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.forename: Zihan
authors.initials: Z
authors.lastname: Poh
authors.forename: Anandhkumar
authors.initials: A
authors.lastname: Raju
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.forename: Edward G
authors.initials: EG
authors.lastname: Robins
mesh_terms: D000792:Angiography / Q000379:methods*; D000818:Animals; D003287:Contrast Media; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000098:blood supply*; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium; D008239:Lysine
keywords: Contrast agent; Gadolinium chelate; Magnetic resonance imaging (MRI); Molecular imaging; Tumor angiography