CMR 2005: 3.05: In vivo follow‐up of Gd‐labeled liposome concentrations in rats bearing a glioma: a comparative study

Abstract

Rationale and Objectives: Cationic liposomes are a tool for targeted delivery of diagnostic and therapeutic compounds to the neovasculature around a solid tumor, due to a preferential binding with activated endothelial cells (1). On this basis, Medigene is developing cationic nanoparticulate carriers (EndoTAG) for tumor therapy and diagnostics (2). Here, innovative Gd-loaded lipid complexes were investigated. A novel technique called monochromatic quantitative computed tomography (MQCT) has recently been implemented at the European Synchrotron Radiation Facility and highlighted as a complementary tool to other imaging techniques in the field of preclinical and contrast medium research (3). It provides in vivo absolute concentration maps of Gd-based contrast agents (CAs) as a function of time with a fair spatial resolution (350 mm) (4). The purpose of this work was to map, as a function of time, Gd concentrations obtained after injection of several kinds of Gd-based liposomes in the rat brain bearing a 9 L glioma. Methods: CAs studied were different types of Gd-labeled cationic and anionic liposomes. In comparison, empty liposomes and free Gd CAs were investigated. The monochromator was tuned in order to allow the simultaneous acquisition of two images sitting above and below the Gd K-edge. The time sequence of the CA was studied by performing the same tomography image (located at the theoretical center of the tumor) from before to up to 4 min after the CA injection at a rate of one image every 4 s. The CA was injected through a jugular catheter (2.5 ml at 60 ml/min). A reference tube filled with 1 mg/mL Gd solution was taped close to the rat brain. Energy subtraction images were subtracted from the pre-injection image. The evolution of the concentration was evaluated as a function of time in several regions of interest, by recording the signal values in 5 pixels: phantom, background, skin, contralateral area, tumor area (divided in a peripheral and a central area when possible), palatin area, tongue and vessels. Results and Conclusion: The signal from the Gd-loaded liposomes could be clearly detected. Different concentration profiles in the blood were found for Gd-loaded liposomes and free Gd. The correlation between the molecular composition of the liposomes and the concentration profile could be revealed. Moreover, specific patterns for tumor accumulation of cationic liposomes were found. The data