title: Quantifying molecular specificity of alphavbeta3 integrin-targeted optical contrast agents with dynamic optical imaging.
abstract: Dynamic fluorescence images were obtained from a subcutaneous human Kaposi's sarcoma tumor (KS1767) model immediately following the intravenous injection of an integrin-targeting cyanine dye conjugate, Cy5.5-c(KRGDf). The fluorescence images, acquired via an intensified charge-coupled device detection system, were used in conjunction with a pharmacokinetic (PK) model to determine kinetic properties of target binding in the presence and absence of a competitive ligand, free c(KRGDf). The results indicate that the conjugate dye behaves similarly in normal tissue to the free Cy5.5 dye while it possesses increased uptake in tumor tissue. The change in pharmacokinetic parameters obtained from dynamic imaging of Cy5.5-c(KRGDf) after administration of c(KRGDf) as a competitive ligand to the integrin receptor suggests that (i) the increased uptake of Cy5.5-c(KRGDf) is molecularly specific and that (ii) receptor turnover occurs within 24 h. In addition, PK analysis enables quantification of an in vivo c(KRGDf) binding constant attributable to integrin binding. In vivo pharmacokinetic analysis based on rapid and dynamic optical imaging may be potentially useful for evaluating the presence and turnover rate of disease markers that are potential targets of molecular medicine.
authors.affiliation: Texas A&M University, Photon Migration Laboratories, College Station, Texas 77843-3012, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gurfinkel
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002232:Carbocyanines / Q000493:pharmacokinetics; D003287:Contrast Media; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D039302:Integrin alphaVbeta3; D009363:Neoplasm Proteins