Cleaved CD31 as a target for in vivo molecular imaging of inflammation.

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.

Clinical Significance of Ejection Dynamics Parameters in Patients with Aortic Stenosis: An Outcome Study.

BACKGROUND: Ejection dynamics parameters are useful in assessing prosthetic valve obstruction, but very limited data are available in the setting of native aortic stenosis (AS). The aim of this study was to evaluate and compare the prognostic value of acceleration time (AT) and the ratio of AT to ejection time (ET) in patients with AS. METHODS: AT and AT/ET were prospectively measured in 456 patients with AS (aortic valve area < 1.3 cm2; mean aortic valve area, 0.85 ± 0.24 cm2). The relationships between AT/ET, AT, and mortality during follow-up were studied. RESULTS: During a median follow-up period of 35 months (interquartile range, 33-37 months), 124 patients died. After adjustment for variables of prognostic importance, including mean pressure gradient, stroke volume index, and aortic valve replacement as a time-dependent covariate, patients in the highest tertiles of both AT/ET (>0.36) and AT (>112 msec) were at high risk for overall mortality (adjusted hazard ratios, 2.44 [95% CI, 1.46-4.08; P = .001] and 1.78 [95% CI, 1.06-2.98; P = .029], respectively) compared with those in the lowest tertiles of AT/ET and AT, while survival was similar for the other tertiles (P = NS for all). Compared with patients with AT/ET ≤ 0.36, an increased risk for overall mortality was observed in patients with AT/ET > 0.36 (adjusted hazard ratio, 2.51; 95% CI, 1.66-3.78; P < .0001), while the risk for mortality was not significantly increased in patients with AT > 112 msec compared with those with AT ≤ 112 msec. Adding AT/ET > 0.36 to a multivariate model including classical variables of prognostic importance, including mean pressure gradient and stroke volume index, improved predictive performance in terms of overall mortality, with improved global model fit, reclassification, and better discrimination. CONCLUSIONS: Among ejection dynamics parameters in patients with AS, AT/ET is strongly associated with excess risk for death during follow-up. AT/ET should be considered in the multiparametric echocardiographic prognostic assessment of patients with AS in clinical practice.