Quantitative analysis of intratumoral infusion of color molecules

Intratumoral infusion has a potential for improving distribution of drugs. To optimize the infusion, we developed a novel technique to quantify the distribution volume of color molecules (Vd) in solid tumors. Evans blue-labeled albumin was infused locally with the use of a needle into a rat fibrosarcoma ex vivo under different pressures. After the infusion, tumor tissues were sectioned serially into thin slices. The blue area in each slice was quantified with the use of the newly developed technique. The Vd was calculated based on the blue area and the slice thickness. Our data showed that infusion pressure and volume (V(i)) had significant effects on Vd. The median of Vd/V(i) decreased from 2.99 to 1.79 when infusion pressure was increased from 50 to 163 cmH2O, presumably due to retardation of convective transport. In addition, the coefficient of variation in Vd/V(i) was increased from 0.13 at 50 cmH2O to 0.64 at 163 cmH2O. The dependence of Vd/V(i) and its variation on infusion pressure suggests that 1) infusion-induced tissue deformation is unpredictable and 2) both the unpredictability and the interstitial retardation of convective transport increase with infusion pressure.