Successful outcomes for patients with cancer often depend on the early detection of tumor and the prompt initiation of active therapy. Despite major advances in the treatment of many cancers, early-stage lesions often go undetected due to the suboptimal resolution of current anatomical and functional imaging modalities. This limitation also applies to preclinical animal tumor models that are crucial for the evaluation and development of new therapeutic approaches to cancer. We report a new mouse model of metastatic pheochromocytoma, generated using tail vein injection of the mouse pheochromocytoma cell (MPC) line that reproducibly generated multiple liver tumors in the animals. Furthermore, we show that in vivo microCT imaging enhanced using a hepatobiliary-specific contrast agent, glyceryl-2-oleyl-1,3-di-7-(3-amino-2,4,6-triiodophenyl)-heptanoate (DHOG), detected tumors as small as 0.35 mm as early as 4 weeks after the injection of the tumor cells. This model may be useful for in vivo studies of tumor biology and for development of new strategies to treat metastatic pheochromocytoma. ' 2006 Wiley-Liss, Inc.

A series of glyceryl 2-oleoyl 1,3-bis[omega-(3-amino-2,4,6-triiodophenyl)] alkanoates was synthesized, radioiodinated with iodine-125, emulsified, and evaluated for their ability to selectively localize in the liver for potential use as hepatographic agents in computed tomography. All seven analogs displayed rapid liver uptake wherein between 65 and 78% of the injected dose accumulated in the liver by 30 min. Liver values ranged from 46 to 93% 3 h after injection which corresponded to liver to blood ratios ranging from 21 to 450. Moreover, subsequent elimination of radioactivity from the liver was nearly linear with respect to alkyl chain length. Analogs with longer alkyl chain length were eliminated from the liver more rapidly than their shorter chain counterparts. Because of their biochemical similarities to naturally occurring triglycerides, these novel analogs may prove useful not only for high-resolution anatomic imaging of focal liver lesions, but also for evaluating a variety of diffuse diseases known to affect hepatic function and biochemistry.

No abstract

A synthetic lipid emulsion (LE) has been developed with physicochemical properties that closely resemble those of a specific class of naturally-occurring lipoproteins known as chylomicron remnants. The formulation has the potential to serve as a hepatocyte-selective delivery system for any lipophilic or amphipathic compounds that can be associated with the internal lipid phase of the emulsion. In the present studies, a lipophilic polyiodinated triglyceride (ITG) was successfully incorporated into the delivery vehicle to form a stable chylomicron-remnant-like emulsion capable of localizing material to the liver following intravenous injection. The preferred ITG-LE formulation was shown to have a mean particle diameter of less than 200 nm and a particle size stability profile in excess of 12 months. The viscosity, pH, and osmolality of the formulation also appeared favorable for safe and convenient intravenous injection. The particle size profile, chemical properties, and high degree of incorporation of ITG into the emulsion suggest that the ITG-LE formulation holds substantial promise as a hepatocyte-selective imaging agent for computed tomography of the liver. Biodistribution, elimination, and computed tomography (CT) imaging results in animals corroborated the hepatocyte-selective nature of the ITG-LE formulation.

In the animal model tested, DHOG-LE imaging efficacy was directly related to iodine dose and was independent of formulation composition. Thus, administration of DHOG-LE in highly concentrated lipid preparations minimized administered dose volume and resulted in appreciable liver enhancement, even at the lowest dose of 50 mg I/kg.