ORIGINAL ARTICLE Multimodal Contrast Agent for Combined Computed Tomography and Magnetic Resonance Imaging Applications Jinzi Zheng, BASc,* Gregory Perkins, BSc,† Anna Kirilova, BSc,† Christine Allen, PhD,‡§ and David A. Jaffray, PhD*†¶ Objective: The objective of this study was to examine the feasibility of a multimodal system to effectively induce and maintain contrast enhancement in both computed tomography (CT) and magnetic resonance (MR) for radiation therapy applications. Materials and Methods: The physicochemical characteristics of a liposome-encapsulated iohexol and gadoteridol formulation were assessed in terms of agent loading efficiencies, size and morphology, in vitro stability, and release kinetics. The imaging properties of the liposome formulation were assessed based on T 1 and T 2 relaxivity measurements and in vitro CT and MR imaging in a phantom. A preliminary imaging-based evaluation of the in vivo stability of this multimodal contrast agent was also performed in a lupine model. Results: The average agent loading levels achieved were 26.5  3.8 mg/mL for iodine and 6.6  1.5 mg/mL for gadolinium. These concentrations correspond to approximately 10% of that found in the commercially available preparations of each of these agents. How- ever, this liposome-based formulation is expected to have a smaller volume of distribution and prolonged circulation lifetime in vivo. This multimodal system was found to have high agent retention in vitro, which translated into maintained contrast enhancement (up to 3 days) and stability in vivo. Conclusions: This study demonstrated the feasibility of engineering a multimodal contrast agent with prolonged contrast enhancement in vivo for use in CT and MR. This contrast agent may serve as a valuable tool for cardiovascular imaging as well as image registra- tion and guidance applications in radiation therapy. Key Words: multimodality imaging, computed tomography (CT), magnetic resonance imaging (MR), contrast agent, liposome (Invest Radiol 2006;41: 339 –348) I n recent years, there has been an increase in the use of multimodality imaging (ie, computed tomography/positron emission tomography, computed tomography/single photon emission computed tomography, x-ray/magnetic resonance imaging system (XMR). 1–8 Because each medical imaging modality has unique strengths and limitations, it is often through the compound use of multiple modalities that the complete assessment of a patient is achieved. Interest in the area of multimodality imaging has also been prompted by the realiza- tion that such techniques offer much more sophisticated characterization of the morphology and physiology of tissues and organs, and that confidence gained in the accurate cor- respondence or registration of different modalities greatly enhances their value. 9 This improved value of imaging will ultimately allow for advances in diagnosis and evaluation of disease, image-guided therapeutic interventions, and assess- ment of treatment outcomes. The recent integration of com- puted tomography (CT) and positron emission tomography (PET) systems is a good example of the advantages of the multimodal approach. 1–3 The CT-PET combination has rev- olutionized the utilization of PET in diagnostic applications because it has been shown to increase the specificity of PET-based assessment by accurately placing the diseased structure within the body frame. 10 –12 In the context of radi- ation therapy, there is a need to merge CT and magnetic resonance (MR) imaging; CT is used for 3-dimensional volumetric radiation dose calculation and MR is used for accurate delineation of the target and normal structures. 13 For example, accurate delineation and targeting of the prostate gland in radiation therapy for prostate cancer necessitates parallel use of CT and MR imaging. 14 Furthermore, CT technology in the form of conventional and cone-beam sys- tems is used on a daily basis to guide the delivery of radiation therapy on treatment machines. 15,16 The development of a multimodal CT and MR contrast agent with the ability to facilitate target delineation and assist in the guidance of Received June 27, 2005 and accepted for publication, after revision, Sep- tember 4, 2005. From the Departments of *Medical Biophysics, ‡Pharmaceutical Sciences, §Chemistry, Chemical Engineering and Applied Chemistry, and ¶Radi- ation Oncology, University of Toronto, Toronto, Ontario, Canada; and the †Radiation Medicine Program, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. This work was funded in part by the Premier’s Research Excellence Award, the Fidani Chair in Radiation Physics, and the support of Susan Grange. Reprints: David A. Jaffray, PhD, Radiation Medicine Program, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, 610 University Avenue, Rm. 5-631, Toronto, Ontario, Canada, M5G 2M9. E-mail: david.jaffray@rmp.uhn.on.ca. Copyright © 2006 by Lippincott Williams & Wilkins ISSN: 0020-9996/06/4103-0339 Investigative Radiology • Volume 41, Number 3, March 2006 339