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Macrophage ablation significantly reduces uptake of imaging probe into organs of the reticuloendothelial system
Bastian O Sabel1,2, Karsten Brand3, Johannes Rueckel2
1Department of Radiology, German Cancer Research Center, Heidelberg, Germany.
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.
Insights
Macrophage ablation reduces contrast agent enhancement in organs like the liver and spleen. This new animal model helps study and control how imaging probes are taken up by macrophages.
Area of Science:
- Biomedical Imaging
- Cell Biology
- Pharmacokinetics
Background:
- Macrophages play a crucial role in engulfing particulate contrast media, essential for biomedical imaging.
- Understanding macrophage-mediated clearance is key to optimizing imaging probe kinetics.
Purpose of the Study:
- To establish a macrophage ablation animal model for investigating imaging probe kinetics.
- To demonstrate the model's utility in manipulating the behavior of contrast agents.
Main Methods:
- Compared computed tomography (CT) contrast media kinetics in macrophage-ablated mice versus control mice.
- Administered clodronate-loaded liposomes to ablate macrophages, followed by ExiTron nano 6000 injection.
- Analyzed CT values in liver and spleen at multiple time points post-injection.
Main Results:
- Macrophage ablation significantly decreased liver and spleen enhancement compared to controls.
- Peak contrast enhancement was lower in ablated mice (liver: 225 CTV, spleen: 431 CTV) versus controls (liver: 582 CTV, spleen: 974 CTV).
- Observed statistically significant differences (P=0.032 for liver, P=0.016 for spleen).
Conclusions:
- Macrophage ablation reduces contrast agent enhancement in macrophage-rich organs.
- This model offers new avenues for studying and manipulating imaging probe uptake via phagocytic activity.
- Highlights the impact of macrophage function on the pharmacokinetics of particulate imaging agents.
