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Background: Macrophages engulf particulate contrast media, which is pivotal for biomedical imaging., Purpose: To introduce a macrophage ablation animal model by showing its power to manipulate the kinetics of imaging probes., Material and Methods: The kinetics of a particulate computed tomography (CT) contrast media was compared in macrophage ablative mice and normal mice. Liposomes (size 220 µg), loaded with clodronate, were injected into the peritoneum of three C57BL/6 mice. On the third day, 200 µL of the particulate agent ExiTron nano 6000 were injected into three macrophage-ablative mice and three control mice. CT scans were acquired before and 3 min, 1 h, 6 h, and 24 h after the ExiTron application. The animals were sacrificed, and their spleens and livers removed. Relative CT values (CTV) were measured and analyzed., Results: Liver and spleen enhancement of treated mice and controls were increasing over time. The median peak values were different with 225 CTV for treated mice and 582 CTV for controls in the liver ( P  = 0.032) and 431 CTV for treated and 974 CTV in controls in the spleen ( P  = 0.016)., Conclusion: Macrophage ablation leads to a decrease of enhancement in organs containing high numbers of macrophages, but only marginal changes in macrophage-poor organs. Macrophage ablation can influence the phagocytic activity and thus opens new potentials to investigate and manipulate the uptake of imaging probes.

Cardiac perfusion studies using computed tomography are a common tool in clinical practice. Recent technical advances and the availability of dedicated small animal scanners allow the transfer of these techniques to the preclinical sector in general and to mouse models of cardiac diseases in particular. This necessitates new requirements for contrast injection techniques as a rapid transport of contrast media from the intravenous access to the animal heart. Clinical contrast agents containing high iodine concentrations are used within small animal studies although they exhibit a high viscosity which might limit their transport within the vasculature. The authors provide a comparison of the transport of contrast media following an injection into the lateral tail vein and an injection into the retrobulbar sinus and discuss the anatomy involved. The temporal evolution of a contrast bolus and its in vivo distribution is visualized. It is demonstrated that injecting contrast agents into the lateral tail vein of mice results in a retrograde blood flow to the liver veins and therefore does not deliver a detectable contrast bolus to the heart, and thus it cannot be used for cardiac perfusion studies. By contrast, boli injected into the retrobulbar sinus are rapidly transported to the heart and provide ventricular contrast enabling perfusion studies similar to those in human patients. The results demonstrate that an injection into the retrobulbar sinus is superior to an injection into the lateral tail vein for the delivery of contrast boli to the animal heart, while all drawbacks of an injection into the lateral tail vein are overcome.

Antibody-conjugated gold nanoparticles have been applied as a biologically targeted contrast agent in live mice for one of the most widely used medical imaging methods, X-ray computed tomography. Such nanoprobes directed toward the CD4 receptor lead to distinctly enhanced X-ray contrast of peripheral lymph nodes. This study demonstrates the general feasibility of biologically specific X-ray imaging in living animals and discusses basic requirements for the use of nanoparticles as a targeted X-ray contrast agent.

Recently we described iodinated homopolymeric radiopaque nanoparticles of 28.9+/-6.3 nm dry diameter synthesized by emulsion polymerization of 2-methacryloyloxyethyl(2,3,5-triiodobenzoate) (MAOETIB). The nanoparticle aqueous dispersion, however, was not stable and tended to agglomerate, particularly at weight concentration of dispersed nanoparticles above approximately 0.3%. The agglomeration rate increases as the concentration of nanoparticles in aqueous phase rises and prevents the potential in vivo use as contrast agent for medical X-ray imaging. Here we describe efforts to overcome this limitation by synthesis of iodinated copolymeric nanoparticles of 25.5+/-4.2 nm dry diameter, by emulsion copolymerization of the monomer, MAOETIB, with a low concentration of glycidyl methacrylate (GMA). The surface of resulting copolymeric nanoparticles is far more hydrophilic than that of polyMAOETIB (PMAOETIB) nanoparticles. Therefore, P(MAOETIB-GMA) nanoparticles are significantly more stable against agglomeration in aqueous continuous phase. After intravenous injection of P(MAOETIB-GMA) nanoparticles in rats and mice (including those with a liver cancer model) CT-imaging revealed a significant enhanced visibility of the blood pool for 30 min after injection. Later, lymph nodes, liver and spleen strongly enhanced due to nanoparticle uptake by the reticuloendothelial system. This favorably enabled the differentiation of cancerous from healthy liver tissue and suggests our particles for tumor imaging in liver and lymph nodes.