Positive effects of polyethylene glycol conjugation to generation-4 polyamidoamine dendrimers as macromolecular MR contrast agents

Hisataka Kobayashi, Satomi Kawamoto, Tsuneo Saga, Noriko Sato, Akira Hiraga, Takayoshi Ishimori, Junji Konishi, Kaori Togashi, Martin W. Brechbiel

Research output: Contribution to journalArticlepeer-review

Abstract

Macromolecules conjugated with polyethylene glycol (PEG) acquire more hydrophilicity, resulting in a longer half-life in circulation and lower immunogenicity. Two novel conjugates for MRI contrast agents were synthesized from a generation-4 polyamidoamine dendrimer (G4D), 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M), and one or two PEG molecules with a molecular weight of 20000 Da (PEG2-G4D-(1B4M-Gd)62 (MW: 96 kD), PEG1-G4D- 1B4M-Gd)63 (MW: 77 kD)). Their pharmacokinetics, excretion, and properties as vascular MRI contrast agents were evaluated and compared with those of G4D-(1B4M-Gd)64 (MW: 57 kD). PEG2-G4D-(1B4M-Gd)62 remained in the blood significantly longer and accumulated significantly less in the liver and kidney than the other two preparations (P < 0.01). Although the blood clearance was slower, PEG2-G4D-(1B4M-Gd)62 was excreted more readily without renal retention than the other two preparations. In conclusion, the positive effects of PEG conjugation on a macromolecular MRI contrast agent were found to be prolonged retention in the circulation, increased excretion, and decreased accumulation in the organs.

Original languageEnglish (US)
Pages (from-to)781-788
Number of pages8
JournalMagnetic resonance in medicine
Volume46
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Contrast agent
  • MRI
  • Macromolecular
  • Polyamidoamine dendrimer
  • Polyethylene glycol

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint

Dive into the research topics of 'Positive effects of polyethylene glycol conjugation to generation-4 polyamidoamine dendrimers as macromolecular MR contrast agents'. Together they form a unique fingerprint.

Cite this