Intrabiliary RF Heat-enhanced Local Chemotherapy of a Cholangiocarcinoma Cell Line: Monitoring with Dual-Modality Imaging—Preclinical Study

Abstract

Purpose:To determine whether magnetic resonance (MR) imaging heating guidewire-mediated radiofrequency (RF) hyperthermia could enhance the therapeutic effect of gemcitabine and 5-fluorouracil (5-FU) in a cholangiocarcinoma cell line and local deposit doses of chemotherapeutic drugs in swine common bile duct (CBD) walls. Materials and Methods:The animal protocol was approved by the institutional animal care and use committee. Green fluorescent proteinlabeled human cholangiocarcinoma cells and cholangiocarcinomas in 24 mice were treated with (a) combination therapy with chemotherapy (gemcitabine and 5-FU) plus RF hyperthermia, (b) chemotherapy only, (c) RF hyperthermia only, or (d) phosphate-buffered saline. Cell proliferation was quantified, and tumor changes over time were monitored with 14.0-T MR imaging and optical imaging.To enable further validation of technical feasibility, intrabiliary local delivery of gemcitabine and 5-FU was performed by using a microporous balloon with (eight pigs) or without (eight pigs) RF hyperthermia. Chemotherapy deposit doses in the bile duct walls were quantified by means of high-pressure liquid chromatography. The nonparametric Mann-Whitney U test and the paired-sample Wilcoxon signed rank test were used for data analysis. Results:Combination therapy induced lower mean levels of cell proliferation than chemotherapy only and RF hyperthermia only (0.39 6 0.13 [standard deviation] vs 0.87 6 0.10 and 1.03 6 0.13, P , .001). Combination therapy resulted in smaller relative tumor volume than chemotherapy only and RF hyperthermia only (0.65 6 0.03 vs 1.30 6 0.021 and 1.37 6 0.05, P = .001). Only in the combination therapy group did both MR imaging and optical imaging show substantial decreases in apparent diffusion coefficients and fluorescent signals in tumor masses immediately after the treatments. Chemotherapy quantification showed a higher average drug deposit dose in swine CBD walls with intrabiliary RF hyperthermia than without it (gemcitabine: 0.32 mg/g of tissue 6 0.033 vs 0.260 mg/g 6 0.030 and 5-FU: 0.660 mg/g 6 0.060 vs 0.52 mg/g 6 0.050, P , .05). Conclusion:The use of intrabiliary MR imaging heating guidewiremediated RF hyperthermia can enhance the chemotherapeutic effect on a human cholangiocarcinoma cell line and local drug deposition in swine CBD tissues.q RSNA, 2013

Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status

“…2). Tumor cells in the peripheral zone become more vulnerable to chemotherapy and radiotherapy [26,27,30,31]. …”

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

“…Statistical software (SPSS 19.0; SPSS, Chicago, Ill) was used for all data analyses (8). A nonparametric MannWhitney U test was used to compare (a) relative proliferation rates among different cell groups; (b) relative optical signal intensity values; and (c) relative tumor volumes at different time points among the animal groups with various mice, and chemotherapeutic drug solutions at 100 mL per 100 mm 3 tumor were injected into tumors.…”

“…Luciferase-and red fluorescence protein-positive cells were sorted by using a fluorescenceactivated cell sorting technique (Aria II; Becton Dickinson, Franklin Lakes, NJ). Cells were then seeded in four-chamber enable delivery of high doses of chemotherapeutic agents into target tissue with improved tumoricidal activity but fewer systemic adverse effects (8,9). Recent studies have confirmed that nonablative hyperthermia at approximately 42°C can significantly enhance the sensitivity of cancer cells to chemotherapeutic drugs and reverse chemotherapy resistance (10)(11)(12).…”

“…Generation of external hyperthermia in the esophagus poses the risk of injury to adjacent vital organs, such as the spinal cord (15,16). In the past decade, we have developed a U.S. Food and Drug Administration-approved magnetic resonance (MR) imaging heating guidewire that can be used not only for highspatial-resolution luminal wall imaging and guiding interventions but also may be applied as an intraluminal heating source for enhancing local gene and chemotherapy treatment (8,17,18). The purpose of this study was to determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance the effect of local chemotherapy in rats with orthotopic esophageal squamous cancers.…”

Interventional MRI-guided local delivery of agents into swine bile duct walls using MR-compatible needle-integrated balloon catheter system

“…MRI‐guided minimally invasive interventional technology permits local delivery of high‐dose drug to target tissues, which thus overcome the key drawback of systemic chemotherapeutic drug administration – toxicity to other vital organs. Recent efforts have been made to develop an intrabiliary local agent delivery approach, which may enable one to instantly monitor and evaluate the chemotherapeutic drug delivery efficacy of intrabiliary local agent delivery under MRI . This new technique involved the use of a multiporous balloon catheter that was percutaneously placed into the common bile duct (CBD), where chemotherapeutic drugs were locally infused into CBD walls.…”