Molecular Imaging of Matrix Metalloproteinase Activation to Predict Murine Aneurysm Expansion In Vivo

Journal of Nuclear Medicine

Lei Nie¹  Sina Tavakoli¹  Albert J. Sinusas¹  D. Scott Edwards¹  Lawrence W. Dobrucki¹  Mahmoud Razavian¹  Mehran M. Sadeghi¹  Niema Razavian¹  Michael Azure¹  Jiasheng Zhang¹ 

关键词: nuclear imaging;    matrix metalloproteinases;    aneurysm;   

DOI  :  10.2967/jnumed.110.075259

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Rupture and dissection are major causes of morbidity and mortality in arterial aneurysm and occur more frequently in rapidly expanding aneurysms. Current imaging modalities provide little information on aneurysm beyond size. Matrix metalloproteinase (MMP) activation plays a key role in the pathogenesis of aneurysm. We investigated whether imaging MMP activation in aneurysm helps predict its propensity to expansion. Methods: We used a model of carotid aneurysm in apolipoprotein E–deficient (apoE−/−) mice. Radiotracers with specificity for activated MMPs were used to detect and quantify MMP activation by micro-SPECT/CT in vivo. Tracer uptake was confirmed by autoradiography and γ-well counting, and specificity was demonstrated using an excess of unlabeled precursor and a specific MMP inhibitor. Results: We demonstrated that several MMPs are expressed with distinct temporal patterns in aneurysm. Significant focal uptake was observed in aneurysmal carotid arteries, peaking at 4 wk after aneurysm induction. In a group of animals imaged serially at 2 and 4 wk after aneurysm induction, MMP tracer uptake at 2 wk correlated well with the vessel area assessed by histology at 4 wk. Conclusion: Molecular imaging of MMP activation is a useful experimental, and potentially clinical, tool to noninvasively predict the propensity of an aneurysm to expansion in vivo.

【 授权许可】

Unknown