title: Imaging of homeostatic, neoplastic, and injured tissues by HA-based probes.
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.
authors: Division of Life Sciences, Lawrence Berkeley National Laboratories, Berkeley, California, USA.
authors: Mandana
authors: M
authors: Veiseh
authors: Daniel
authors: D
authors: Breadner
authors: Jenny
authors: J
authors: Ma
authors: Natalia
authors: N
authors: Akentieva
authors: Rashmin C
authors: RC
authors: Savani
authors: Rene
authors: R
authors: Harrison
authors: David
authors: D
authors: Mikilus
authors: Lisa
authors: L
authors: Collis
authors: Stefan
authors: S
authors: Gustafson
authors: Ting-Yim
authors: TY
authors: Lee
authors: James
authors: J
authors: Koropatnick
authors: Leonard G
authors: LG
authors: Luyt
authors: Mina J
authors: MJ
authors: Bissell
authors: Eva A
authors: EA
authors: Turley
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry / Q000494:pharmacology; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D041622:Tomography, Optical / Q000379:methods*; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology
chemical_list: D015335:Molecular Probes; D006820:Hyaluronic Acid