Tracking the relative in vivo pharmacokinetics of nanoparticles with PARACEST MRI

M. Meser Ali, Byunghee Yoo, Mark D. Pagel

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

A noninvasive assay that tracks the relative in vivo pharmacokinetics of two nanoparticles may accelerate the development of nanoparticles for biomedical applications, and may provide a method to select personalized nanomedicines for individual patients. To develop an in vivo competitive assay, two MRI contrast agents that could be selectively detected through paramagnetic chemical exchange saturation transfer (PARACEST) were conjugated to a second generation and fifth generation polyamidoamine (PAMAM) dendrimer. The CEST effects of each agent was calibrated relative to concentration. The effects of T1 relaxivities of these dendritic PARACEST magnetic resonance imaging (MRI) contrast agents were found to be negligible relative to their CEST effects with respect to changes in image contrast, which facilitated the measurement of the ratios of their chemical exchange lifetimes. Injection of both contrast agents into a mouse model of mammary carcinoma resulted in a temporal increase in the CEST effect from each agent in the flank tumor. Although the in vivo CEST effects could not be used to determine the absolute concentrations of each agent within the tumor, the ratio of the in vivo CEST effects was used to measure the ratio of the concentrations of the agents. This result demonstrated that the relative in vivo pharmacokinetics of two nanoparticles may be evaluated using PARACEST MRI.

Original languageEnglish (US)
Pages (from-to)1409-1416
Number of pages8
JournalMolecular Pharmaceutics
Volume6
Issue number5
DOIs
StatePublished - Oct 5 2009

Keywords

  • Breast cancer
  • Contrast agents
  • Dendrimers
  • MRI
  • Pharmacokinetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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