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Lys-Thr-Leu-Leu-Pro-Thr-Pro-cross-linked iron oxide-Cy5.5.


Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2008 Aug 08 [updated 2011 Feb 22].


Optical fluorescence imaging is increasingly being used to obtain images of biological functions of specific targets in vitro and in small animals (1, 2). Near-infrared (NIR) fluorescence (700–900 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues. NIR fluorescence imaging is becoming a non-invasive alternative to radionuclide imaging in vitro and in small animals. Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used to create images because of their abundance in water molecules, which comprise >80% of most soft tissues. The contrast of proton MRI images depends mainly on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal; T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the use of contrast agents. Most contrast agents affect the T1 and T2 relaxation of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (3). Cross-linked iron oxide (CLIO) and other iron oxide formulations affect T2 primarily and lead to a decreased signal. A multimodal nanoparticle probe that consists of a contrast agent and a NIR fluorochrome may provide consistent information. CLIO nanoparticles can be internalized by cells of the reticuloendothelial system and have long circulating times in vivo. The blood half-life of CLIO is ~10 h in mice (4). The accumulation of nanoparticles in cells causes a reduction in signal intensity with T2-weighted (T2*W) spin-echo pulse sequences. NIR fluorochromes (e.g., Cy5.5) provide an improved optical (NIR) signal from tissue. CLIO-Cy5.5 has been developed as a multimodal probe for imaging (5). Patients with pancreatic ductal adenocarcinoma (PDAC) have a median survival of 6 months and a 5-year survival rate of only 3% (6). PDAC is an aggressive cancer with early metastasis in >80% of patients. A method for early detection would be particularly useful for monitoring people at high risk of developing pancreatic cancer. Using phage display screenings, the linear peptide Lys-Thr-Leu-Leu-Pro-Thr-Pro (Plectin-1 targeting peptide, PTP) (7) has been found to specifically bind to Plectin-1, a cytoskeletal protein (8, 9) that is present both inside and on the membrane of human and mouse PDAC cells but only on the inside of normal pancreatic cells. Kelly et al. (7) conjugated PTP to CLIO-Cy5.5 to image Plectin-1 expression in PDAC. PTP-CLIO-Cy5.5 is a multimodal agent that consists of CLIO (MRI) and Cy5.5 (NIR imaging).

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