Effect of Transcatheter Intra-Arterial Therapies on Tumor Interstitial Fluid Pressure and Its Relation to Drug Penetration in a Rabbit Liver Tumor Model

Purpose: To determine the change in tumor interstitial fluid pressure (IFP) after transcatheter intra-arterial (IA) therapies and its relation to drug penetration in liver cancer.; Materials and Methods: VX2 tumors were grown in the livers of 16 rabbits. The rabbits were treated with intravenous injection of doxorubicin (group 1; n = 4), hepatic IA injection of doxorubicin (group 2; n = 4), hepatic IA injection of doxorubicin followed by embolization with polyvinyl alcohol particles (group 3; a = 4), or hepatic IA injection of doxorubicin mixed with Lipiodol followed by polyvinyl alcohol embolization (group 4; n = 4). Tumor IFP was measured with a Milcro-Tip pressure catheter before and 1 hour after treatment. Doxorubicin penetration was evaluated by immunofluorescence. Results: Tumor IFP after treatment decreased by 5.0% +/- 2.8, 3.9% +/- 9.0, 27.1% +/- 5.2, and 31.8% +/- 7.4 in groups 1-4, respectively. The difference in IFP reduction between embolization-treated groups (groups 3 and 4) and nonembolized groups (groups 1 and 2) was significant (P < .001). Doxorubicin penetration distances were 20.3 mu m +/- 3.7, 45.7 mu m +/- 10.5, 69.5 mu m +/- 9.3, and 47.9 mu m +/- 6.4 in groups 1-4, respectively. IFP reduction was significantly correlated with doxorubicin penetration distance (r = .671, P = .004). Conclusions: A greater reduction of tumor IFP was associated with embolization in a preclinical liver tumor model, and embolization may indirectly contribute to increased drug penetration.