EBM: Fluorescent + MRI sensitive nanoprobes help to image tumor angiogenesis

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Integrin-specific, fluorescent super paramagnetic nanoprobes are capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model, offering opportunities for early detection of solid tumors and non-invasive post-therapy assessment of antiangiogenic drugs, according to a study published in the August issue of Experimental Biology and Medicine.

"Imaging tumor angiogenesis is important in early detection, tumor stratification and post-therapy assessment of antiangiogenic drugs," said the study's senior author Jinming Gao, PhD, a professor at the University of Texas Southwestern Medical Center at Dallas. "The dual functional nanoprobes aim to image angiogenesis-specific tumor markers that are overly expressed in the tumor vasculature during the early phase of angiogenesis."

Chase Kessinger, carried out the work as part of his PhD thesis in cancer molecular imaging at the University of Texas Southwestern. The research team relied on nanotechnology and established super paramagnetic micellar nanoprobes (50-70 nm in diameter) with greatly improved MRI sensitivity over conventional small molecular agents.

The nanoprobe surface was functionalized with integrins that specifically bind to tumor endothelial cells and had a fluorescent moiety used for the validation of targeted delivery to the tumor endothelial cells. The researchers validated the increased uptake of nanoprobes compared to non-targeted-nanoparticles in cancer cells.

In collaboration with Masaya Takahashi, PhD, an associate professor in the advanced imaging research center and co-workers at University of Texas Southwestern Medical Center, the research team employed a 3D high resolution acquisition method to visualize the accumulation of the micelle nanoprobes in tumors.

"Conventional image analysis of angiogenesis relies on the evaluation of 'hot spot' densities in 2D images. The 3D high resolution method allowed for the connection of the isolated 'hot spots' in 2D slices into 3D network structures, which greatly improves the accuracy of vessel identification and quantification," Gao said.

In preclinical animal tumor models, MR imaging of the targeted contrast probes yielded vascularized network structures in 3D tumor images. The enhanced visualization allowed for a more accurate quantification of tumor angiogenesis. The results showed significant increase of contrast specificity of angiogenic vessels by the targeted nanoprobes over non-targeted micelles. These targeted nanoprobes may provide a useful contrast probe design for the clinical diagnosis of tumor angiogenesis.

"Kessinger et al working at the interface of nanotechnology, material science, and the clinical imaging modality MRI have created a nanosized probe capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model," wrote Steven R. Goodman, PhD, editor-in-chief of Experimental Biology and Medicine. "This should be an important tool for clinical observation of tumor angiogenesis."