An Extracellular MRI Polymeric Contrast Agent That Degrades at Physiological pH

被引:21
作者
Schopf, Eric [1 ]
Sankaranarayanan, Jagadis [1 ]
Chan, Minnie [3 ]
Mattrey, Robert [4 ]
Almutairi, Adah [1 ,2 ]
机构
[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept NanoEngn, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Chem, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA
基金
美国国家科学基金会;
关键词
contrast agents; polyketal; extracellular degradation; Gd(III) complexes; bioresponsive; NEPHROGENIC SYSTEMIC FIBROSIS; DTPA CYSTINE COPOLYMERS; ENHANCED MRI; GADOLINIUM(III) COMPLEXES; LUMINESCENT PROBES; PHARMACOKINETICS; BIODISTRIBUTION; RETENTION; PEG-G-POLY(GDDTPA-CO-L-CYSTINE); STRATEGIES;
D O I
10.1021/mp2005998
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Macromolecular contrast agents have the potential to assist magnetic resonance imaging (MRI) due to their high relaxivity, but are not clinically useful because of toxicity due to poor clearance. We have prepared a biodegradable ketal-based polymer contrast agent which is designed to degrade rapidly at physiological pH by hydrolysis, facilitating renal clearance. In vitro, the agent degraded more rapidly at lower pH, with complete fragmentation after 24 h at pH 7.4. In vitro relaxivity measurements showed a direct correlation between molecular weight and relaxivity. We compared our polymer contrast agent with commercially available Magnevist in vivo by MRI imaging, as well as measuring the Gd concentration in blood. Our results show that our polymer contrast agent gives a higher contrast and intensity in the same organs and areas as Magnevist and is cleared from the blood at a similar rate. We aim to improve our polymer contrast agent design to develop it for use as a MRI contrast agent, and explore its use as a platform for other imaging modalities.
引用
收藏
页码:1911 / 1918
页数:8
相关论文
共 50 条
  • [41] VSION as high field MRI T1 contrast agent: evidence of their potential as positive contrast agent for magnetic resonance angiography
    Vangijzegem, T.
    Stanicki, D.
    Boutry, S.
    Paternoster, Q.
    Vander Elst, L.
    Muller, R. N.
    Laurent, S.
    [J]. NANOTECHNOLOGY, 2018, 29 (26)
  • [42] Dynamic Susceptibility Contrast MRI with a Prebolus Contrast Agent Administration Design for Improved Absolute Quantification of Perfusion
    Knutsson, Linda
    Lindgren, Emelie
    Ahlgren, Andre
    van Osch, Matthias J. P.
    Bloch, Karin Markenroth
    Surova, Yulia
    Stahlberg, Freddy
    van Westen, Danielle
    Wirestam, Ronnie
    [J]. MAGNETIC RESONANCE IN MEDICINE, 2014, 72 (04) : 996 - 1006
  • [43] Manganese-Based Layered Double Hydroxide Nanoparticles as a T1-MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity
    Li, Bei
    Gu, Zi
    Kurniawan, Nyoman
    Chen, Weiyu
    Xu, Zhi Ping
    [J]. ADVANCED MATERIALS, 2017, 29 (29)
  • [44] Application of a Biodegradable Macromolecular Contrast Agent in Dynamic Contrast-Enhanced MRI for Assessing the Efficacy of Indocyanine Green-Enhanced Photothermal Cancer Therapy
    Feng, Yi
    Emerson, Lyska
    Jeong, Eun-Kee
    Parker, Dennis L.
    Lu, Zheng-Rong
    [J]. JOURNAL OF MAGNETIC RESONANCE IMAGING, 2009, 30 (02) : 401 - 406
  • [45] Preclinical Safety Assessment of Gadopiclenol: A High-Relaxivity Macrocyclic Gadolinium-Based MRI Contrast Agent
    Gendron, Celia
    Bourrinet, Philippe
    Dencausse, Anne
    Fretellier, Nathalie
    [J]. INVESTIGATIVE RADIOLOGY, 2024, 59 (02) : 108 - 123
  • [46] Three-dimensional MRI of coronary arteries using an intravascular contrast agent
    Li, DB
    Dolan, RP
    Walovitch, RC
    Lauffer, RB
    [J]. MAGNETIC RESONANCE IN MEDICINE, 1998, 39 (06) : 1014 - 1018
  • [47] IRON-OXIDE NANOPARTICLES FOR USE AS AN MRI CONTRAST AGENT - PHARMACOKINETICS AND METABOLISM
    POULIQUEN, D
    LEJEUNE, JJ
    PERDRISOT, R
    ERMIAS, A
    JALLET, P
    [J]. MAGNETIC RESONANCE IMAGING, 1991, 9 (03) : 275 - 283
  • [48] A novel cholic acid-based contrast enhancement agent for targeted MRI
    Chong, Hyun-Soon
    Song, Hyun A.
    Lim, Sooyoun
    Macrenaris, Keith
    Ma, Xiang
    Lee, Haisung
    Bui, Phuong
    Meade, Thomas
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (07) : 2505 - 2508
  • [49] A Novel Mesoporous Superparamagnetic Hybrid Silica/Hydroxyapatite Nanocomposite as MRI Contrast Agent
    Kermanian, Mehraneh
    Sadighian, Somayeh
    Ramazani, Ali
    Naghibi, Mehran
    Hosseini, Seyed Hojjat
    [J]. CHEMNANOMAT, 2021, 7 (03) : 284 - 291
  • [50] Biomedical Applications of Gadolinium-Containing Biomaterials: Not Only MRI Contrast Agent
    Pan, Xingtong
    Hu, Menglong
    Wu, Likun
    Wei, Erfan
    Zhu, Qiyue
    Lv, Letian
    Xv, Xiuyun
    Dong, Xinyi
    Liu, Hao
    Liu, Yunsong
    [J]. ADVANCED SCIENCE, 2025,