title: Near-infrared optical imaging of integrin alphavbeta3 in human tumor xenografts.
abstract: In vivo optical imaging is potentially useful for evaluating the presence of tumor markers that are targets of molecular medicine. Here we report the synthesis and characterization of integrin alphavbeta3-targeted peptide cyclo(Lys-Arg-Gly-Asp-Phe) [c(KRGDf )] labeled with fluorescence dyes with wavelength spanning from the visible/near infrared (Cy5.5) to the true near infrared (IRDye800) for optical imaging. In vitro, the peptide-dye conjugates bound specifically to tumor cells expressing alphavbeta3. When administered intravenously into mice at a dose of 6 nmol /mouse, the conjugates accumulated in tumors expressing alphavbeta3. The tumor-to-background ratios for human KS1767 Kaposi's sarcoma in mice injected with Cy5.5-c(KRGDf ) and Cy5.5 were 5.5 and 1.5, respectively. Preinjection of c(KRGDf ) blocked the uptake of Cy5.5-c(KRGDf ) in tumors by 89%. In alphavbeta3-positive M21 and alphavbeta3-negative M21-L human melanoma, fluorescence intensity in the tumor of mice injected with IRDye800 - c(KRGDf ) was 2.3 and 1.3 times that in normal tissue, respectively. Dynamic imaging revealed that Cy5.5- c(KRGDf ) was rapidly taken up by KS1767 tumor immediately after bolus injection. The rate of its uptake in the tumor was reduced by preinjection of c(KRGDf ) in an interval time-dependent manner. Our data suggest that near-infrared fluorescence imaging may be applied to the detection of tumors expressing integrin alphavbeta3 and to the assessment of the optimal biological dose and schedule of targeted therapies.
authors.affiliation: Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.forename: Qingping
authors.initials: Q
authors.lastname: Wu
authors.forename: Chusilp
authors.initials: C
authors.lastname: Charnsangavej
authors.forename: Mikhail
authors.initials: M
authors.lastname: Gurfinkel
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002232:Carbocyanines; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010456:Peptides, Cyclic; D012514:Sarcoma, Kaposi / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic