title: Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent.
abstract: In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd(3+), the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,α=0.43 h, t1/2,β=2.32 h), much longer than 0.11h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast.
authors.affiliation: Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712, Republic of Korea.
authors.forename: Ratchapol
authors.initials: R
authors.lastname: Jenjob
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Na
authors.initials: N
authors.lastname: Kun
authors.affiliation: Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7-50, Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Ghee
authors.affiliation: Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201, China.
authors.forename: Zheyu
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Liberal Arts and Science, GIST College, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: scho@gist.ac.kr.
authors.forename: Steve K
authors.initials: SK
authors.lastname: Cho
authors.affiliation: Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7-50, Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea; Department of Internal Medicine, School of Medicine, Inha University Hospital, Incheon 420-751, Republic of Korea.
authors.forename: Don Haeng
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712, Republic of Korea. Electronic address: Sugeun.Yang@Inha.ac.kr.
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005936:Glucans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats
chemical_list: D003287:Contrast Media; D005936:Glucans; C009109:pullulan; D019786:Gadolinium DTPA
keywords: Chelation stability; Extended blood circulation; Gadolinium-DTPA; Nephrogenic fibrosis; Transmetalation