Chemodosimetry of in vivo tumor liposomal drug concentration using MRI.

Published

Journal Article

Effective cancer chemotherapy depends on the delivery of therapeutic drugs to cancer cells at cytotoxic concentrations. However, physiologic barriers, such as variable vessel permeability, high interstitial fluid pressure, and heterogeneous perfusion, make it difficult to achieve that goal. Efforts to improve drug delivery have been limited by the lack of noninvasive tools to evaluate intratumoral drug concentration and distribution. Here we demonstrate that tumor drug concentration can be measured in vivo using T(1)-weighted MRI, following systemic administration of liposomes containing both drug (doxorubicin (DOX)) and contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using T(1) relaxation times and Mn:DOX loading ratios, as previously described. Two independent validations by high-performance liquid chromatography (HPLC) and histologic fluorescence in a rat fibrosarcoma (FSA) model indicate a concordant linear relationship between DOX concentrations determined using T(1) and those measured invasively. This method of imaging exhibits potential for real-time evaluation of chemotherapeutic protocols and prediction of tumor response on an individual patient basis.

Full Text

Duke Authors

Cited Authors

  • Viglianti, BL; Ponce, AM; Michelich, CR; Yu, D; Abraham, SA; Sanders, L; Yarmolenko, PS; Schroeder, T; MacFall, JR; Barboriak, DP; Colvin, OM; Bally, MB; Dewhirst, MW

Published Date

  • November 2006

Published In

Volume / Issue

  • 56 / 5

Start / End Page

  • 1011 - 1018

PubMed ID

  • 17029236

Pubmed Central ID

  • 17029236

Electronic International Standard Serial Number (EISSN)

  • 1522-2594

International Standard Serial Number (ISSN)

  • 0740-3194

Digital Object Identifier (DOI)

  • 10.1002/mrm.21032

Language

  • eng