(427c) Determining Diffusion Parameters of Rat Tumor Tissue Using Fluorescent Visualization Methods

The transport of effective doses of anti-cancer tumor drugs to solid tumors is very challenging due to the barriers imposed by the characteristics of the tumor and its vasculature [1]. Furthermore, drug metabolizability, the body's natural removal process, and binding to non-target cells [2] make complete utilization of the drug impossible. Thus, in order to quantify the effectiveness of the anti-cancer drug, a thorough understanding of the transport mechanisms within the tumor is needed.

The objective of this study is to quantify the difference in diffusion rates as a function of the solute concentration, solute type and location in the tumor. The study proposes a constitutive model that quantifies drug transport to a solid tumor using solute transport concepts and validates the parameters of the model with clinical data. The proposed model emphasizes the transport mechanisms for the general case, since there are many different anti-cancer drugs and many different types of solid cancer tumors. The effects of transport limitations will be analyzed using a parametric sensitivity analysis.

The clinical portion of the study estimates diffusion parameters for the model. Using rat models, tumors are grown and harvested. The tumor tissue is exposed to a known concentration of fluorescent dye in a series of designed experiments. Cross sections of the tumor are examined visually using images captured with low light cameras, frame grabbers, and light filters. Image analysis uses linear absorption theory to detect the concentration gradient of the dye. The digitized gray-level values are calibrated to a relative solute concentration at the pixel scale. Diffusion coefficients and normalized cumulative mass within the various compartments of the tumor tissue are calculated from the relative concentration data. The study uses different dye concentration and the fluorescent dye methodology to provide evidence for the importance of diffusion in tumors.

This work will present the experiment and scientific methods to collect the data. The role of diffusion and other factors using the constitutive model with the estimated diffusion parameters will be discussed.

References [1] R.K. Jain (1997) Delivery of molecular and cellular medicine to solid tumors. Micro-circulation, 4(1):1--23.

A. David, F. Yuan, M. Leuing, and R.K. Jain (1997) Direct in vivo measurement of targeted binding in a human tumor xenograft. Biophysics , volume 94, pages 1785--1790.