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EJNMMI Research (1)
Molecular Imaging and Biology (1)
Herzog, Eva (2)
Ntziachristos, Vasilis (2)
Razansky, Daniel (2)
Ale, Angelica (1)
Buehler, Andreas (1)
Harlaar, Niels J. (1)
Hillebrands, Jan Luuk (1)
Smith, Bradley D (1)
Taruttis, Adrian (1)
Zeebregts, Clark J. (1)
van Dam, Gooitzen M. (1)
Year of Publication
High resolution tumor targeting in living mice by means of multispectral optoacoustic tomography
Smith, Bradley D
Tumor targeting is of high clinical and biological relevance, and major efforts have been made to develop molecular imaging technologies for visualization of the disease markers in tissue. Of particular interest is apoptosis which has a profound role within tumor development and has significant effect on cancer malignancy.
Herein, we report on targeting of phosphatidylserine-exposing cells within live tumor allograft models using a synthetic near infrared zinc(II)-dipicolylamine probe. Visualization of the probe biodistribution is performed with whole body multispectral optoacoustic tomography (MSOT) system and subsequently compared to results attained by planar and tomographic fluorescence imaging systems.
Compared to whole body optical visualization methods, MSOT attains remarkably better imaging capacity by delivering high-resolution scans of both disease morphology and molecular function in real time. Enhanced resolution of MSOT clearly showed that the probe mainly localizes in the vessels surrounding the tumor, suggesting that its tumor selectivity is gained by targeting the phosphatidylserine exposed on the surface of tumor vessels.
The current study demonstrates the high potential of MSOT to broadly impact the fields of tumor diagnostics and preclinical drug development.
Optoacoustic imaging; Tumor targeting; Molecular imaging; Phosphatidylserine targeting
Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques
Harlaar, Niels J.
Hillebrands, Jan Luuk
Zeebregts, Clark J.
van Dam, Gooitzen M.
Molecular Imaging and Biology
Elevated expression of cathepsins, integrins and matrix metalloproteinases (MMPs) is typically associated with atherosclerotic plaque instability. While fluorescent tagging of such molecules has been amply demonstrated, no imaging method was so far shown capable of resolving these inflammation-associated tags with high fidelity and resolution beyond microscopic depths. This study is aimed at demonstrating a new method with high potential for noninvasive clinical cardiovascular diagnostics of vulnerable plaques using high-resolution deep-tissue multispectral optoacoustic tomography (MSOT) technology.
Methods and results
MMP-sensitive activatable fluorescent probe (MMPSense™ 680) was applied to human carotid plaques from symptomatic patients. Atherosclerotic activity was detected by tuning MSOT wavelengths to activation-dependent absorption changes of the molecules, structurally modified in the presence of enzymes. MSOT analysis simultaneously provided morphology along with heterogeneous MMP activity with better than 200 micron resolution throughout the intact plaque tissue. The results corresponded well with epi-fluorescence images made from thin cryosections. Elevated MMP activity was further confirmed by in situ zymography, accompanied by increased macrophage influx.
We demonstrated, for the first time to our knowledge, the ability of MSOT to provide volumetric images of activatable molecular probe distribution deep within optically diffuse tissues. High-resolution mapping of MMP activity was achieved deep in the vulnerable plaque of intact human carotid specimens. This performance directly relates to pre-clinical screening applications in animal models and to clinical decision potential as it might eventually allow for highly specific visualization and staging of plaque vulnerability thus impacting therapeutic clinical decision making.
Atherosclerosis; Optoacoustic imaging; Carotid arteries; Plaque; Contrast media; Inflammation; Medicine & Public Health; Imaging / Radiology
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