Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate targeted to alpha v beta 3 receptor expressed in Kaposi's sarcoma.
Dynamic fluorescence images were obtained from xenografts bearing a subcutaneous human Kaposi's sarcoma (KS1767) immediately following the intravenous injection of an integrin-receptor targeting Cy5.5-c(KRGDf) at a dose ranging from 0.75 to 6 nmol/mouse. The fluorescence images were acquired using an intensified charge-coupled device system and were analyzed with a three-compartment pharmacokinetic (PK) model to determine uptake parameters in the tumor and normal tissue regions of interest as a function of administered dose. Our results show that the uptake of Cy5.5-c(KRGDf) in tumor regions were: (i) significantly greater than the contralateral normal tissue regions; (ii) linearly increased with dose of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse; and (iii) blocked by preinjection of c(KRGDf). Above doses of 1.5 nmol/mouse, the uptake no longer increased with dose, suggesting integrin receptor saturation. In normal tissues, the PK uptake parameters were not influenced by Cy5.5-c(KRGDf) dose nor by the preadministration of c(KRGDf).
Kwon
Sunkuk
S
Texas A&M University, TX 77842-3012, USA.
Ke
Shi
S
Houston
Jessica P
JP
Wang
Wei
W
Wu
Qingping
Q
Li
Chun
C
Sevick-Muraca
Eva M
EM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000493:pharmacokinetics*; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology*; D013194:Staining and Labeling
D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid