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Positive effects of polyethylene glycol conjugation to generation‐4 polyamidoamine dendrimers as macromolecular MR contrast agents
Author(s) -
Kobayashi Hisataka,
Kawamoto Satomi,
Saga Tsuneo,
Sato Noriko,
Hiraga Akira,
Ishimori Takayoshi,
Konishi Junji,
Togashi Kaori,
Brechbiel Martin W.
Publication year - 2001
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.1257
Subject(s) - dendrimer , peg ratio , polyethylene glycol , chemistry , conjugated system , macromolecule , kidney , renal physiology , mri contrast agent , pegylation , gadolinium , biochemistry , renal function , medicine , organic chemistry , polymer , finance , economics
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 (PEG 2 ‐G4D‐(1B4M‐Gd) 62 (MW: 96 kD), PEG 1 ‐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). PEG 2 ‐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, PEG 2 ‐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. Magn Reson Med 46:781–788, 2001. © 2001 Wiley‐Liss, Inc.