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

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Abstract

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; n = 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 Mikro-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 μm ± 3.7, 45.7 μm ± 10.5, 69.5 μm ± 9.3, and 47.9 μm ± 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.

Section snippets

Animal Model, Magnetic Resonance Imaging, and Study Groups

The present study was approved by the animal care and use committee of our institution. Adult New Zealand White rabbits (body weight, 2.5–3.0 kg) were purchased from the Center for Experimental Animals of Huazhong University of Science and Technology. The strain of VX2 tumor was maintained by successive implantation into the thigh of carrier rabbits. Tumor implantation was performed by using an aseptic technique, and general anesthesia was introduced with intravenous (IV) sodium pentobarbital

Results

The pretreatment mean tumor sizes are shown in Table 1. There were no significant differences between groups in tumor largest diameter (P = .978) and tumor volume (P = .994).

In all 16 rabbits, the pretreatment IFP in the tumor center was significantly higher than in the adjacent normal liver tissue (27.3 mm Hg ± 6.1 and 12.7 mm Hg ± 5.7, respectively; P < .001). Table 2 and Figure 2 summarize the pre- and postprocedural tumor IFPs and the IFP percentage change in the four groups at 1 hour after

Discussion

Drug penetration in tumor is a complex and dynamic process, and many factors that affect drug penetration may affect the final efficacy of chemotherapy (6, 9). Although systemic chemotherapy is ineffective for liver cancer, improved efficacy of transcatheter techniques with chemotherapy have shed new light on the implications of chemotherapy for this tumor. A previous study showed that embolization improved drug penetration in liver cancer (4), but the mechanism has not been adequately studied.

Acknowledgment

This research was supported by National Natural Sciences Foundation of China Grants 81101134 and 81471765.

References (20)

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None of the authors have identified a conflict of interest.

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