Journal
BIOMACROMOLECULES
Volume 13, Issue 1, Pages 12-22Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm201143c
Keywords
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Funding
- DOD-BCRP IDEA [BC044087]
- U.S. Department of Energy, Office of Biological and Environmental Research
- Low Dose Radiation Program [DE-AC02-05CH1123]
- National Cancer Institute [R37CA064786, U54CA126552, R01CA057621, U54CA112970, U01CA143233, U54CA143836]
- U.S. Department of Defense [W81XWH0810736]
- Hyal Pharma Corp. (Mississauga, ON, Canada)
- National Institute of Health [HL075930, HL62472, HL62868]
- Canadian Institutes of Health Research [MOP82720]
- Ruth L. Kirschstein National Research Service
- National Cancer Institute of National Institute of Health [FCA132491A]
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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, Tc-99m-HA, and iodine-HA, I-125-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (Tc-99m-HA), breast cancer. cells/xenografts (TR-HA, Gd-HA), and vascular injury (I-125-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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