Purpose Preclinical imaging of endothelial activation and mineralization using both positron emission tomography (PET) and magnetic resonance (MR) remains scarce. Procedures A group of uremic ApoE −/− (Ur), non-uremic ApoE −/− (NUr), and control C57Bl/6 J mice (Ctl) were investigated. Mineralization process was assessed using sodium fluoride ([18F]NaF) PET, and MR imaging combined with intravenous injection of MPIO-αVCAM-1 was used to evaluate endothelial activation. Micro- and macrocalcifications were evaluated by flame atomic absorption spectroscopy and von Kossa staining, respectively. Results Ur mice showed an active and sustained mineralization process compared to Ctl mice ( p = 0.002) using [18F]NaF PET imaging. Calcium plasma level was increased in Ur (2.54 ± 0.09 mM, n = 17) compared to NUr and Ctl mice (2.24 ± 0.01, n = 22, and 2.14 ± 0.02, n = 27, respectively; p < 0.0001). Likewise, vascular calcium content was increased in Ur (0.51 ± 0.06 μg Ca 2+ per milligram of dry weight aorta, n = 11) compared to NUr (0.27 ± 0.05, n = 9, p = 0.013) and Ctl (0.28 ± 0.05, n = 11, p = 0.014). Ur mice also had a higher inflammatory state using MPIO-αVCAM-1 MR ( p global = 0.01, post hoc analysis Ur vs. Ctl p = 0.003) associated with increased VCAM-1 expression ( p global = 0.02). Aortic remodeling at the level of the brachiocephalic trunk, brachiocephalic trunk itself, and aortic arch in Ur mice was also demonstrated using MR. Conclusions Preclinical molecular imaging allowed in vivo characterization of the early phase of atherosclerosis. [18F]NaF PET showed early and sustained vascular mineralization in uremic ApoE −/− mice. MPIO-αVCAM-1 MR imaging demonstrated aortic endothelial activation, predominantly in segments with vascular remodeling.
There is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before 99mTc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [18F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of 99mTc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of 99mTc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellent in vitro and in vivo stability were observed. SPECT/CT imaging showed a significant higher 99mTc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [18F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between 99mTc-HYNIC-D-P8RI uptake and inflammatory cell infiltration. 99mTc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specific in vivo imaging of inflammatory processes.
Optimizing reconstruction parameters significantly impacted on the assessment of mineralization process in a preclinical model of accelerated atherosclerosis using Na[F]F PET. In addition, improving the CT resolution was associated with a dramatic radiation dose increase.
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