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.