Physiologically based pharmacokinetics of molecular imaging nanoparticles for mRNA detection determined in tumor-bearing mice.

Authors

Armin W Opitz, Department of Chemical Engineering, Center for Molecular and Engineering Thermodynamics, University of Delaware
Eric Wickstrom, Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Mathew L Thakur, Department of Radiology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Norman J Wagner, Department of Chemical Engineering, Center for Molecular and Engineering Thermodynamics, University of Delaware

Document Type

Article

Publication Date

6-1-2010

Comments

This article has been peer reviewed and is published in Oligonucleotides 2010 Jun;20(3):117-25. The published version is available at DOI: 10.1089/oli.2009.0216. ©Mary Ann Liebert, Inc

Abstract

Disease detection and management might benefit from external imaging of disease gene mRNAs. Previously we designed molecular imaging nanoparticles (MINs) based on peptide nucleic acids complementary to cancer gene mRNAs. The MINs included contrast agents and analogs of insulin-like growth factor 1 (IGF-1). Analysis of MIN tumor uptake data showed stronger binding in tumors than in surrounding tissues. We hypothesized that MINs with an IGF-1 analog stay in circulation by binding to IGF-binding proteins. To test that hypothesis, we fit the tissue distribution results of several MINs in xenograft-bearing mice to a physiological pharmacokinetics model. Fitting experimental tissue distribution data to model-predicted mass transfer of MINs from blood into organs and tumors converged only when the parameter for MINs bound to circulating IGF-binding proteins was set to 10%-20% of the injected MIN dose. This result suggests that previous mouse imaging trials used more MINs than necessary. This prediction can be tested by a ramp of decreasing doses.

Recommended Citation

Opitz, Armin W; Wickstrom, Eric; Thakur, Mathew L; and Wagner, Norman J, "Physiologically based pharmacokinetics of molecular imaging nanoparticles for mRNA detection determined in tumor-bearing mice." (2010). Kimmel Cancer Center Faculty Papers. Paper 17.
https://jdc.jefferson.edu/kimmelccfp/17

PubMed ID

20406142