Development of an Intrabiliary MR Imaging-monitored Local Agent Delivery Technique: A Feasibility Study in Pigs

Abstract

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 contrastto-noise ratio for the CBD after administration of the mixture, compared with images obtained prior to MGd/ trypan blue administration (11.6 6 4.2 [standard deviation] vs 5.7 6 2.8; P = .04). Histologic results depicted the blue dye stains and red fluorescence of MGd in CBD walls, confirming the imaging findings.

Gliomas: Motexafin Gadolinium-enhanced Molecular MR Imaging and Optical Imaging for Potential Intraoperative Delineation of Tumor Margins

“…Results of previous studies (19)(20)(21)(22) have confirmed that MGd can be internalized exclusively in metabolically active tissues, such as atherosclerotic plaques and different tumors. It also can cross the disrupted blood-brain barrier associated with brain tumors, but it is not detectable in normal brains (18,23,24).…”

“…Qiu et al T1-weighted MR imaging contrast agent, and a red fluorescence emitter (19)(20)(21). In the current study, we attempted to investigate the application of MGd for intraoperative imagingguided complete glioma resection.…”

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

“…Among these new techniques is the application of an intraluminal MR imaging-radiofrequency (RF) heat system, with the key component being a Food and Drug Administration-approved MR imaging heating guidewire. The MR imaging heating guidewire has three major functions, acting as (a) an intraluminal MR receiver antenna for generating high-spatial-resolution MR imaging of luminal walls (14,15), (b) a conventional guidewire for guiding intraluminal interventional procedure (16,17), and (c) an intraluminal RF hyperthermia source for enhancing gene delivery (18). This "three-in-one" function of simultaneous imaging, guiding, and heating may provide an opportunity to solve the current clinical problems in the management of biliary malignancies.…”

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

“…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).…”