Noninvasive optical imaging of ovarian metastases using Cy5-labeled RAFT-c(-RGDfK-)4.
Our group has developed a new molecular tool based on the use of a regioselectively addressable, functionalized template (RAFT) scaffold, where four cyclic (Arg-Gly-Asp) (cRGD) peptide motifs were grafted. The aim of this study was to determine whether RAFT-c(-RGDfK-)4 combined with optical imaging could allow noninvasive detection of deep ovarian metastases. Human ovarian adenocarcinoma IGROV1 cells expressing low levels of integrin alphaVbeta3 (the main receptor for the cRGD peptide) were used for in vitro and in vivo assays in combination with Cy5-labeled RAFT-c(-RGDfK-)4, cRGD, or RAFT-c(-RbetaADfK-)4. In vivo fluorescence imaging was performed on subcutaneous (SC) tumors and intraperitoneal IGROV1 metastases in nude mice. The accumulation of RGD-Cy5 conjugates in cultured cells or in tumor tissues was examined using confocal laser scanning microscopy. RAFT-c(-RGDfK-)4 exhibited stronger staining in vitro, enhanced tumor-to-background ratio for sc tumors, and allowed early detection of 1- to 5-mm large intraabdominal nodules using noninvasive optical imaging. Histological study revealed that RAFT-c(-RGDfK-)4 accumulated into tumor neovasculature but also into tumor cells. Our data demonstrate that a Cy5-labeled RAFT-c(-RGDfK-)4 is an efficient optical probe for early and noninvasive tumor detection.
Jin
Zhao-Hui
ZH
Institut Albert Bonniot, France.
Josserand
Veronique
V
Razkin
Jesus
J
Garanger
Elisabeth
E
Boturyn
Didier
D
Favrot
Marie-Christine
MC
Dumy
Pascal
P
Coll
Jean-Luc
JL
D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007269:Injections, Intra-Arterial; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D010456:Peptides, Cyclic / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D011860:Radiography, Abdominal; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D002232:Carbocyanines; D002352:Carrier Proteins; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D011108:Polymers; C085321:cyanine dye 5; C507169:cyclic arginine-glycine-aspartic acid peptide