Citation Details

Journal Article

Molecular imaging; Abdominal aortic aneurysm; Optical imaging; Pre-clinical; Endovascular imaging; Matrix metalloproteinase; in vivo imaging; MMPSense

Objectives: We present a method to quantify the inflammatory processes that drive abdominal aortic aneurysm (AAA) development that may help predict the rate of growth and thus guide medical and surgical management. We use an in vivo optical molecular imaging approach to quantify protease activity within the walls of AAAs in a rodent model.

Methods: AAAs were generated in mice by topical application of calcium chloride, followed by the administration of the MMP inhibitor doxycycline for 3 months. After this time period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity was administered, and MMP proteolytic activity was measured in vivo. Histology and in situ zymography were performed for validation. AAAs were also generated in rats, and MMP activity within the walls of the AAAs was also quantified endovascularly.

Results: A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated, with high doses of the drug resulting in nearly complete suppression of aneurysm formation. There was a direct relationship between the rate of aneurysmal growth and measured MMP activity, with a linear best-fit well approximating the relationship. We additionally performed endovascular imaging of AAAs in rats and demonstrated a similar suppression of intramural MMP activity following doxycycline administration.

Conclusions: We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents and show a direct, linear relationship between proteolytic activity and aneurysmal growth. We also illustrate that this functional imaging method can be performed endovascularly, demonstrating potential pre-clinical and clinical applications.

Journal Article

Inflammation; Calcification; Atherosclerosis; Molecular imaging; in vivo imaging; ProSense; OsteoSense

Optical molecular imaging represents an emerging method that can detect pathobiological processes in vivo at the cellular and molecular levels, offering a dynamic link between imaging and biology. This review discusses the impact of molecular imaging methods in atherosclerosis research and preventive medicine and focuses on the inflammation-dependent mechanisms of arterial calcification.

Journal Article

in vivo imaging; Cat K FAST; Cat B FAST; MMPSense

New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.

Journal Article

Beta-cells; GLP1-R; imaging; targeting; in vivo imaging; VivoTag; AngioSense; Diabetes

The ability to image and ultimately quantitate beta-cell mass in vivo will likely have far reaching implications in the study of diabetes biology, in the monitoring of disease progression or response to treatment, as well as for drug development. Here, using animal models, we report on the synthesis, characterization of, and intravital microscopic imaging properties of a near infrared fluorescent exendin-4 analogue with specificity for the GLP-1 receptor on beta cells (E4K12-Fl). The agent demonstrated sub-nanomolar EC50 binding concentrations, with high specificity and binding could be inhibited by GLP-1R agonists. Following intravenous administration to mice, pancreatic islets were readily distinguishable from exocrine pancreas, achieving target-to-background ratios within the pancreas of 6:1, as measured by intravital microscopy. Serial imaging revealed rapid accumulation kinetics (with initial signal within the islets detectable within 3 minutes and peak fluorescence within 20 minutes of injection) making this an ideal agent for in vivo imaging.

Journal Article

bone marrow cells; Cancer; cell labeling; in vitro; in vivo imaging; Olympus IV-100; tail vein injection; VivoTag 750

Mucosal damage is a common side effect of many cancer treatments, especially radiotherapy and intensive chemotherapy, which often induce bone marrow (BM) suppression. We observed that acetic acid- (AA-) induced mucosal damage in the colon of mice was worsened by simultaneous treatment with irradiation or 5-FU. However, irradiation 14 days prior to the AA treatment augmented the recovery from mucosal damage, suggesting that the recovery from BM suppression had an advantageous effect on the mucosal repair. In addition, BM transplantation also augmented the recovery from AA-induced mucosal damage. We further confirmed that transplanted BM-derived cells, particularly F4/80+Gr1+ “inflammatory” monocytes (Subset 1), accumulated in the damaged mucosal area in the early healing phase, and both of Subset 1 and F4/80+Gr1^- “resident” monocytes (Subset 2) accumulated in this area in later phases. Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy.