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

234 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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