title: Evaluation of Nonpeptidic Ligand Conjugates for SPECT Imaging of Hypoxic and Carbonic Anhydrase IX-Expressing Cancers.
abstract: As tumors grow, vasculature is often deficient or malformed, resulting in many localized areas of hypoxia. Cells located in these hypoxic regions exhibit an altered gene expression pattern that can significantly alter resistance to conventional anticancer treatments such as ionizing radiation and chemotherapeutic drugs. A priori knowledge of the level of hypoxia within a tumor may better guide clinical care. In an effort to create a hypoxia specific imaging agent, a ligand for the tissue hypoxia marker, carbonic anhydrase IX (CA IX), was synthesized and used as a targeting ligand to deliver an attached (99m)Tc-chelating agent. Binding of the resulting conjugates to hypoxic cancer cells was first characterized in vitro. Whole animal imaging and biodistribution studies then were performed to determine tumor specificity in vivo. Several conjugates were found to bind selectively to CA IX expressing tumors in a receptor-dependent manner. We suggest that such conjugates could prove useful in identifying hypoxic cancers and/or quantitating the level of hypoxia within a tumor.
authors.affiliation: Institute 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: Institute 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: Institute 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 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D000072258:Tumor Hypoxia
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D008024:Ligands; D012235:Rhodamines; D011092:Polyethylene Glycols; D013667:Technetium; D000071231:Carbonic Anhydrase IX