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Comparison of Fenestra LC, ExiTron nano 6000, and ExiTron nano 12000 for Micro-CT Imaging of Liver and Spleen in Mice

Posted Aug 31, 2013 Updated Apr 10, 2023
By Hanne Boll MVD , Giovanna Figueiredo MD , Teresa Fiebig MVD , Stefanie Nittka PhD , Fabian Doyon MD , Hans Ulrich Kerl MD , Ingo Nölte MD , Alex Förster MD , Martin Kramer MVD , Marc A. Brockmann MD
7 min read

Rationale and Objectives

The purpose of this study was to compare different contrast agents for longitudinal liver and spleen imaging in a mouse model of liver metastasis.

Materials and Methods

Mice developing liver metastases underwent longitudinal micro-computed tomography imaging after injection of Fenestra LC, ExiTron nano 6000, or ExiTron nano 12000. Elimination times and contrast enhancement of liver and spleen were compared.

Results

For all contrast agents, liver contrast peaked at approximately 4 hours and spleen contrast at 48 hours postinjection. A single dose of 100 μL of ExiTron nano 6000 or 12000 resulted in longstanding enhancement of liver and spleen tissue for longer than 3 weeks, whereas repeated injections of 400 μL of Fenestra LC were required to retain contrast at acceptable levels and allowed imaging of the liver/spleen for up to 2 and 9 days, respectively.

Conclusion

Both ExiTron nano agents provide longer and stronger contrast enhancement of liver and spleen compared to Fenestra LC, and they do so at a 75% lower injection volume in mice.

Small rodents, especially mice, are frequently used to model and study human diseases. One of the methods used for noninvasive longitudinal monitoring of pathological processes in small animals is micro–computed tomography (micro-CT), which has gained increasing importance in preclinical research within the past decade . For micro-CT imaging of liver disease, high soft tissue contrast is required to detect small pathological lesions such as liver metastases. For this purpose, contrast agents providing a positive (ie, hyperdense) contrast of healthy liver tissue have been developed . One of the hitherto frequently used agents is Fenestra LC, which is selectively taken up by hepatocytes via an apolipoprotein E (apoE) receptor-mediated pathway. As tumor cells usually do not express apoE receptor and do not contain relevant numbers of macrophages, liver-specific contrast agents allow the delineation of the nonenhancing and thus relatively hypodense tumors within the hyperdense healthy liver tissue. Drawbacks of Fenestra LC are a relatively high injection volume of up to 400 μL/20-g mouse as recommended by the manufacturer and the required repeated injections for longitudinal studies due to the relatively short elimination time.

Recently, ExiTron nano, a novel preclinical liver-specific CT contrast agent, has been introduced. This alkaline earth metal–based nanoparticulate contrast agent creates a strong and specific contrast of the reticuloendothelial system (RES) of the liver and the spleen at injection volumes of as low as 100 μL. Furthermore, ExiTron nano provides a long-lasting contrast of the liver and spleen for several weeks after injection.

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Materials and methods

Mouse Model of Liver Metastasis

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Micro-CT Contrast Agents

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Micro-CT Imaging Procedure

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Image Analysis

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Results

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Figure 1, Time course of contrast enhancement within the liver (a) and the spleen (b) of healthy C57BL/6J mice (three per group) after a single tail vein injection of 400 μL of Fenestra LC, 100 μL of ExiTron nano 6000, or 100 μL of ExiTron nano 12000. Measurements were performed by placing a region of interest within the spleen and within the liver, avoiding large intrahepatic vessels. The baseline level (= 100%) refers to measurements of the relative density of the liver and the spleen before administration of the contrast agent. The time course of contrast enhancement after a single tail vein injection of 400 μL of Fenestra LC is exemplarily shown (c) .

Figure 2, Micro–computed tomography (CT) images demonstrating the time course of contrast enhancement of liver tissue after a single intravenous injection of 100 μL of ExiTron nano 12000 (a – d) , 100 μL of ExiTron nano 6000 (c – h), or 400 μL of Fenestra LC (i – l) . Images were acquired before (a,e,i) , and 4 hours (b,f,j) , 48 hours (c,g,k), and 16 days (d,h,l) after a single tail vein injection of contrast agent. Micro-CT scanning parameters: 80 kV, 75 μA; 40-second scan time; 190° rotation; 1200 projections.

Figure 3, Micro–computed tomography (CT) images acquired after a single intravenous injection of 100 μL of ExiTron nano 12000 (a – c) , after a single injection of 400 μL of Fenestra LC (d), and after repeated injections of Fenestra LC (e,f ; after three injections, interval between injections: 2 days). (a,f) Intrasplenic (*) and intrahepatic (LMet) growing tumors. Smallest detectable liver metastases (a , LMet ) measured 300 μm in diameter. (b – f) Contrast enhancement of the abdominal and mediastinal lymph nodes (LN) and of the adrenal glands (AdrG); note the weak contrast enhancement of the LNs and the AdrG after a single injection of Fenestra LC. Micro-CT scanning parameters: 80 kV, 75 μA; 40-second scan time; 190° rotation; 1200 projections. L, liver; S, spleen.

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Discussion

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Academic Radiology, Volume 20, Issue 9
Journals General Radiology
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