Macromolecular MRI contrast agents with small dendrimers

Pharmacokinetic differences between sizes and cores

Hisataka Kobayashi, Satomi Kawamoto, Sang Kyung Jo, Henry L. Bryant, Martin W. Brechbiel, Robert A. Star

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications.

Original languageEnglish
Pages (from-to)388-394
Number of pages7
JournalBioconjugate Chemistry
Volume14
Issue number2
DOIs
Publication statusPublished - 2003 Mar 1
Externally publishedYes

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Dendrimers
Pharmacokinetics
Magnetic resonance imaging
Contrast Media
Gadolinium DTPA
Kidney
Blood Vessels
Blood vessels
Albumins
Imaging techniques

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Macromolecular MRI contrast agents with small dendrimers : Pharmacokinetic differences between sizes and cores. / Kobayashi, Hisataka; Kawamoto, Satomi; Jo, Sang Kyung; Bryant, Henry L.; Brechbiel, Martin W.; Star, Robert A.

In: Bioconjugate Chemistry, Vol. 14, No. 2, 01.03.2003, p. 388-394.

Research output: Contribution to journalArticle

Kobayashi, Hisataka ; Kawamoto, Satomi ; Jo, Sang Kyung ; Bryant, Henry L. ; Brechbiel, Martin W. ; Star, Robert A. / Macromolecular MRI contrast agents with small dendrimers : Pharmacokinetic differences between sizes and cores. In: Bioconjugate Chemistry. 2003 ; Vol. 14, No. 2. pp. 388-394.
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