title: Evaluation of a Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence-Guided Surgery of Hypoxic Tumors.
abstract: Proof-of-principle studies in ovarian, lung, and brain cancer patients have shown that fluorescence-guided surgery can enable removal of otherwise undetectable malignant lesions, decrease the number of cancer-positive margins, and permit identification of disease-containing lymph nodes that would have normally evaded resection. Unfortunately, the current arsenal of tumor-targeted fluorescent dyes does not permit identification of all cancers, raising the need to design new tumor-specific fluorescent dyes to illuminate the currently undetectable cancers. In an effort to design a more universal fluorescent cancer imaging agent, we have undertaken to synthesize a fluorophore that could label all hypoxic regions of tumors. We report here the synthesis, in vitro binding, and in vivo imaging of a near-infrared (NIR) fluorescent dye that is targeted to carbonic anhydrase IX (CA IX), i.e., a widely accepted marker of hypoxic tissues. The low molecular weight NIR probe, named Hypoxyfluor, is shown to bind CA IX with high affinity and accumulate rapidly and selectively in CA IX positive tumors. Because nearly all human cancers contain hypoxic regions that express CA IX abundantly, this NIR probe should facilitate surgical resection of a wide variety of solid tumors.
authors.affiliation: Center for Drug Discovery and ‡Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.affiliation: Center for Drug Discovery and ‡Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Roy
authors.affiliation: Center for Drug Discovery and ‡Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Karson S
authors.initials: KS
authors.lastname: Putt
authors.affiliation: Center for Drug Discovery and ‡Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
mesh_terms: D000818:Animals; D000071231:Carbonic Anhydrase IX / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism* / Q000601:surgery*; D019265:Spectroscopy, Near-Infrared / Q000379:methods
chemical_list: D005456:Fluorescent Dyes; D000071231:Carbonic Anhydrase IX
keywords: CA IX; carbonic anhydrase IX; fluorescence-guided surgery; hypoxia