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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 αVβ3 (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(-RβADfK-)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. [ABSTRACT FROM AUTHOR]

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 αVβ3 (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(-RβADfK-)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. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging (PAI) provides real time non-invasive and contrast agent free monitoring of some endogenous compounds concentrations that provides improved insights into tissue vascularization and oxygenation which are particularly important during tumor progression. This study assessed the input of PAI for examination of melanoma brain metastases in an orthotopic mouse model and further focused on spatial analyses within the tumor tissue. Hemoglobin content appeared to be higher in tumors than in healthy brains. Spatial analyses further showed that angiogenesis was mainly at the tumor periphery. Concomitantly, while healthy brains were highly oxygenated, the tumors were hypoxic and subjected to a gradient of hypoxia from the periphery to the core. In tumor-bearing brains, spectroscopic PAI clearly revealed the presence of melanin, generating a signal 3 times higher than the background signal in healthy brains. When inserted into tissue mimicking phantoms, the photoacoustic signal of B16F10 melanin-containing cells was linearly correlated to their concentration and the detection limit was 625 cells. In vivo biological characterization of tumor models by non-invasive imaging of vasculature and tissue hypoxia represents an interesting opportunity for better understanding cancer progression; it is opening new research prospects to improve diagnostic, therapy, and early assessment of tumor treatment efficacy. [ABSTRACT FROM AUTHOR]