Imaging of homeostatic, neoplastic, and injured tissues by HA-based probes |
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Authors: | Veiseh Mandana Breadner Daniel Ma Jenny Akentieva Natalia Savani Rashmin C Harrison Rene Mikilus David Collis Lisa Gustafson Stefan Lee Ting-Yim Koropatnick James Luyt Leonard G Bissell Mina J Turley Eva A |
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Institution: | Division of Life Sciences, Lawrence Berkeley National Laboratories, Berkeley, California, USA. |
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Abstract: | An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, (99m)Tc-HA, and iodine-HA, (125)I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver ((99m)Tc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury ((125)I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues. |
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