Publications [#63223] of Mark W. Dewhirst

Papers Published

1. Viglianti, B.L. and Ponce, A.M. and Michelich, C.R. and Yu, D. and Abraham, S.A. and Sanders, L. and Yarmolenko, P.S. and Schroeder, T. and MacFall, J.R. and Barboriak, D.P. and Colvin, O.M. and Bally, M.B. and Dewhirst, M.W., Chemodosimetry of in vivo tumor liposomal drug concentration using MRI, Magn. Reson. Med. (USA), vol. 56 no. 5 (2006), pp. 1011 - 18 [mrm.21032]
   (last updated on 2007/04/14)

   Abstract:
   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 T₁-weighted MRI, following systemic administration of liposomes containing both drug (doxorubicin (DOX)) and contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using T₁ 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 T₁ 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

   Keywords:
   biomedical MRI;cancer;cellular biophysics;chromatography;dosimetry;drugs;manganese;patient treatment;tumours;