Vasomodulation of Tumor Blood Flow: Effect on Perfusion and Thermal Ablation Size

Abstract

Blood flow is a key factor in the efficacy of radiofrequency (RF) ablation treatment of solid tumors. We hypothesized that vasoactive drugs can modulate tumor blood flow and thereby improve the outcome of this thermal ablation approach. To verify this hypothesis, we measured the tumor perfusion changes in response to phenylephrine (PE) and hydralazine (HYZ) using a CT perfusion method in a rat subcutaneous tumor model. The coagulation sizes induced by RF ablation alone, RF ablation with PE and RF ablation with HYZ were compared. Results demonstrated that HYZ produced a marked decrease in entire tumor and tumor rim blood flow of 31.1 and 29.1%; while PE insignificantly change tumor blood flow (5.1% decrease in whole tumor and 6.0% decrease in tumor rim). A markedly greater coagulation area (0.59 cm2 ± 0.24) was observed when HYZ was administered before RF ablation. No difference was noted in the coagulation area induced by RF ablation alone or the combination of PE injection followed by RF ablation (0.29 cm2 ± 0.13 vs. 0.30 cm2 ± 0.18). Results suggest that HYZ decreases subcutaneous tumor blood flow and enhances the coagulation size induced by RF ablation. PE has little influence on tumor blood flow and does not improve ablation.

Structural parameters governing activity of Pluronic triblock copolymers in hyperthermia cancer therapy

“…Multiple strategies have been explored to reduce the post-RF ablation tumour recurrence rate. These include instrumentation modifications to increase volume of ablation [23, 24], physiological manipulations to occlude arteries and prevent heat sink, and pharmacological modifications typically serving as adjuvant chemotherapy to increase cell death [25]. Our unique strategy uses Pluronic as a thermosensitiser which on its own has little effect but when coupled with sublethal temperatures as low as 43°C acts in synergy with the hyperthermia to lead to improved cell death.…”

Modeling the dynamics of antibody–target binding in living tumors

“…The antibody plasma pharmacokinetics 14 were described using a twocompartment model with a linear tissue distribution and a linear systemic clearance. The solid tumors were conceptually dissected into two anatomical compartments-stroma-rich and stroma-poor areas-to account for the spatial heterogeneity.…”

“…The value of σ v was set at 0.78, a value reported for subcutaneous xenograft models 13 . The values of Lp and Lr were functions of the tumor blood flow (TBF) 14 , the total tumor volume (Vtumor), and the relative fraction between the two tumor areas (ft), as described in the following equations:…”

Radiofrequency Ablation: Effect of Tumor- and Organ-specific Pharmacologic Modulation of Arterial and Portal Venous Blood Flow on Coagulation Diameter in an N1-S1 Tumor Model

“…Vasoconstrictive agents will constrict normal vessels which will paradoxically increase blood flow into the tumor vessels. Conversely, vasodilating agents will dilate normal vessels and therefore lower resistance within the normal hepatic parenchymal vasculature while the tumor vasculature remains of normal caliber and resistance (13). This will avert blood away from the tumor vessel bed via a “steal” effect.…”