Guanshu Liu PhD, Presenter: Nothing to Disclose

Yuguo Li PhD, Abstract Co-Author: Nothing to Disclose

Yuan Qiao MD, PhD, Abstract Co-Author: Nothing to Disclose

Shibin Zhou MD, PhD, Abstract Co-Author: Nothing to Disclose

Peter C.M. Van Zijl PhD, Abstract Co-Author: Speakers Bureau, Koninklijke Philips Electronics NV License agreement, Koninklijke Philips Electronics NV

Michael T. McMahon PhD, Abstract Co-Author: Co-founder, SenCest, LLC Co-owner, SenCest, LLC

To develop a liposomal system that encapsulates clinically-used iodinated CT/X-ray contrast agent iodixanol to be a CT/MRI bimodal contrast agent, simply using the Chemical Exchange Saturation Transfer (CEST) contrast from the CT agent.

Iodixanol encapsulated liposomes (CT-lipo) were prepared according to literatures using a formulation of DPPC:cholesterol: DSPE-PEG-2000=57:40:3. The size, concentration and encapsulation ratio of CT-lipo were measured following our previous published methods. 24 hours before MRI and CT studies, 500 µL overnight-dialyzed liposomes (1000 mgI/kg) were injected to the tail vein of Balb/c mice carrying subcutaneous CT26 murine colon tumors. In vivo CEST MR images were acquired using previous published methods.6 3D CT images were acquired using an IVIS® Spectrum CT system (Perkin Elmer) with the following parameters: 50 kVp, 1 mA, and 50 msec exposure, totally 720 projections.

The results showed that iodixanol, both in liposomal (~160 nm) and non-liposomal forms, can also be detected using CEST MRI with a relatively high sensitivity at 4.3 ppm. The detection limit is estimated to be ~ 2nM liposomes, or ~1.4mM encapsulated iodixanol. At 24 hours after i.v. injection, mice injected with CT-lipo showed marked enhancement in tumor region, while those injected with blank liposomes (blank-lipo) did not show significant contrast enhancement. In MRI, the tumor of CT-lipo injected mice showed remarkable but non-uniform CEST contrast enhancement at 4.3 ppm as compared to those injected with blank-lipo, with a average tumor contrast enhancement (MTRasym) of 0.8% (n=2 for each group). More studies of CT and MRI acquisitions on additional animals and immunohistological validation are underway.

The present work demonstrated the feasibility of engineering a multimodality imaging system by encapsulating nanosized liposomes with a single clinically used CT contrast agent iodixanol. Our results showed that both CT and MRI could detect reliably the presence of iodixanol-encapsulating liposomes in tumors, enabling the bimodal assessment of tumor vasculature.

The present nanoparticle system can be easily translated to the Clinical for imaging the vasculature of tumorsand monitoring the effect of anti-angiogenic drugs using both MRI and CT.

Liu, G, Li, Y, Qiao, Y, Zhou, S, Van Zijl, P, McMahon, M, Assessing Tumor Vasculature Using a Liposomal CT/MRI Bimodal Contrast Agent.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13044180.html