Published in:
01-11-2007 | Original Article
PET imaging of acute and chronic inflammation in living mice
Authors:
Qizhen Cao, Weibo Cai, Zi-Bo Li, Kai Chen, Lina He, Hui-Cheng Li, Mizhou Hui, Xiaoyuan Chen
Published in:
European Journal of Nuclear Medicine and Molecular Imaging
|
Issue 11/2007
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Abstract
Purpose
In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-α and integrin αvβ3 expression.
Methods
TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. 64Cu-DOTA-etanercept and 64Cu-DOTA-E{E[c(RGDyK)]2}2 were used for PET imaging of TNF-α and integrin αvβ3 expression in both acute and chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography, direct tissue sampling, and immunofluorescence staining were also performed to confirm the non-invasive PET imaging results.
Results
The ear thickness increased significantly and the TNF-α level more than tripled after a single TPA challenge. MicroPET imaging using 64Cu-DOTA-etanercept revealed high activity accumulation in the inflamed ear, reaching 11.1 ± 1.3, 13.0 ± 2.0, 10.9 ± 1.4, 10.2 ± 2.2%ID/g at 1, 4, 16, and 24 h post injection, respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic inflammation and reduced 64Cu-DOTA-etanercept uptake due to lowered TNF-α expression. 64Cu-DOTA-E{E[c(RGDyK)]2}2 uptake in the chronically inflamed ears (after four and eight TPA challenges) was significantly higher than in the control ears and those after one TPA challenge. Immunofluorescence staining revealed increased integrin β3 expression, consistent with the non-invasive PET imaging results using 64Cu-DOTA-E{E[c(RGDyK)]2}2 as an integrin αvβ3-specific radiotracer. Biodistribution and autoradiography studies further confirmed the quantification capability of microPET imaging.
Conclusion
Successful PET imaging of TNF-α expression in acute inflammation and integrin αvβ3 expression in chronic inflammation provides the rationale for multiple target evaluation over time to fully understand the inflammation processes.