PMID- 24138829 OWN - NLM STAT- MEDLINE DCOM- 20140707 LR - 20131104 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 35 IP - 1 DP - 2014 Jan TI - An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography. PG - 327-36 LID - S0142-9612(13)01217-9 [pii] LID - 10.1016/j.biomaterials.2013.10.006 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Yang, Chang-Tong AU - Yang CT AD - 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. FAU - Chandrasekharan, Prashant AU - Chandrasekharan P FAU - He, Tao AU - He T FAU - Poh, Zihan AU - Poh Z FAU - Raju, Anandhkumar AU - Raju A FAU - Chuang, Kai-Hsiang AU - Chuang KH FAU - Robins, Edward G AU - Robins EG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131016 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Contrast Media) RN - 0 (Heterocyclic Compounds) RN - 0 (Organometallic Compounds) RN - 0199MV609F (gadoteridol) RN - AU0V1LM3JT (Gadolinium) RN - K3Z4F929H6 (Lysine) SB - IM MH - Angiography/*methods MH - Animals MH - *Contrast Media MH - Female MH - Gadolinium/administration & dosage/chemistry/pharmacokinetics MH - Half-Life MH - Heterocyclic Compounds/*administration & dosage/chemistry/pharmacokinetics MH - Humans MH - Lysine/*chemistry MH - Magnetic Resonance Imaging/*methods MH - Mice MH - Mice, SCID MH - Neoplasms/*blood supply MH - Organometallic Compounds/*administration & dosage/chemistry/pharmacokinetics MH - Tissue Distribution OTO - NOTNLM OT - Contrast agent OT - Gadolinium chelate OT - Magnetic resonance imaging (MRI) OT - Molecular imaging OT - Tumor angiography EDAT- 2013/10/22 06:00 MHDA- 2014/07/08 06:00 CRDT- 2013/10/22 06:00 PHST- 2013/09/02 00:00 [received] PHST- 2013/10/01 00:00 [accepted] PHST- 2013/10/22 06:00 [entrez] PHST- 2013/10/22 06:00 [pubmed] PHST- 2014/07/08 06:00 [medline] AID - S0142-9612(13)01217-9 [pii] AID - 10.1016/j.biomaterials.2013.10.006 [doi] PST - ppublish SO - Biomaterials. 2014 Jan;35(1):327-36. doi: 10.1016/j.biomaterials.2013.10.006. Epub 2013 Oct 16.