Intrabiliary RF heat-enhanced local chemotherapy of a cholangiocarcinoma cell line: monitoring with dual-modality imaging--preclinical study.

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 protein-labeled 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 ± 0.13 [standard deviation] vs 0.87 ± 0.10 and 1.03 ± 0.13, P < .001). Combination therapy resulted in smaller relative tumor volume than chemotherapy only and RF hyperthermia only (0.65 ± 0.03 vs 1.30 ± 0.021 and 1.37 ± 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 ± 0.033 vs 0.260 mg/g ± 0.030 and 5-FU: 0.660 mg/g ± 0.060 vs 0.52 mg/g ± 0.050, P < .05). CONCLUSION: The use of intrabiliary MR imaging heating guidewire-mediated RF hyperthermia can enhance the chemotherapeutic effect on a human cholangiocarcinoma cell line and local drug deposition in swine CBD tissues.

Development of an intrabiliary MR imaging-monitored local agent delivery technique: a feasibility study in pigs.

PURPOSE: To investigate the feasibility of using magnetic resonance (MR) imaging to monitor intrabiliary delivery of motexafin gadolinium (MGd) into pig common bile duct (CBD) walls. MATERIALS AND METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee. Initially, human cholangiocarcinoma cells were treated with various concentrations of MGd, a compound serving as a T1-weighted MR imaging contrast agent, chemotherapy drug, and cell marker. These cells were then examined by means of confocal microscopy to confirm the intracellular uptake of MGd. In addition, an MGd/trypan blue mixture was locally infused into CBD walls of six cadaveric pigs using a microporous balloon catheter. CBDs of six pigs were infused with saline to serve as controls. Ex vivo T1-weighted MR imaging of these CBDs was performed. For in vivo technical validation, the microporous balloon catheter was placed in the CBD by means of a transcholecytic access to deliver MGd/trypan blue into CBD walls of six living pigs. T1-weighted images were obtained with both a surface coil and an intrabiliary MR imaging guidewire, and contrast-to-noise ratios of CBD walls before and after MGd/trypan blue infusions were compared in the two groups by means of paired t test, with subsequent histologic analysis to confirm the penetration and distribution of the MGd/trypan blue agent into CBD walls. RESULTS: In vitro experiments confirmed uptake of MGd by human cholangiocarcinoma cells. The ex vivo experiments demonstrated the penetration of MGd/trypan blue into the CBD walls. The in vivo experiment confirmed the uptake of MGd/trypan blue, showing an increased contrast-to-noise ratio for the CBD after administration of the mixture, compared with images obtained prior to MGd/trypan blue administration (11.6 ± 4.2 [standard deviation] vs 5.7 ± 2.8; P = .04). Histologic results depicted the blue dye stains and red fluorescence of MGd in CBD walls, confirming the imaging findings. CONCLUSION: It is feasible to use MR imaging to monitor the penetration of locally delivered MGd into pig CBD walls.