Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice

Abstract

BackgroundMicro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging.MethodologyExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano.Principal FindingsAfter a single injection of ExiTron nano the contrast of liver and spleen peaked after 4–8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks.ConclusionsThe nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast.

Micro-CT of rodents: State-of-the-art and future perspectives

“…Because many liver metastases grow on the surface of the liver, a combined strategy of Fenestra VC plus an intraperitoneal injection of extracellular contrast agent was shown to improve tumor volume measurement [139]. Small lesions like liver metastases also have been imaged using a nanoparticle alkaline earth metal-based contrast agent ( ExiTron nano from Miltenyi Biotec GmbH) developed for small animal liver imaging with CT [140]. …”

Nanomedicine for the molecular diagnosis of cardiovascular pathologies

“…Although their toxicity has to be studied, they are supposed to be better tolerated than iodine-based agents. For preclinical studies with micro-CT, development of alkaline earth-based nanoparticles seems promising [65], as they generated strong contrast enhancement of vessels [66,67]. At the best of our knowledge, no clinical application of nanotechnologies for diagnosis of cardiovascular pathologies with CT has been described yet, but preclinical research led to nanosystems based on iodine and on metal nanocrystals (Fig.…”

High-Resolution CT for Small-Animal Imaging Research

“…Because many liver metastases grow on the surface of the liver, a combined strategy of Fenestra VC plus an intraperitoneal injection of extracellular contrast agent was shown to improve the precision and accuracy of tumor volume measurement and enables the quantitation of total tumor burden (Graham et al, 2008). Small lesions like liver metastases have also been imaged using a nanoparticle alkaline earth metal-based contrast agent (Viscover ExiTron nano) developed for small-animal liver CT imaging (Boll et al, 2011).…”