Cy7-(3 S,7 S)-26-Amino-5,13,20-trioxo-4,6,12,21-tetraazahexacosane-1,3,7,22-tetracarboxylic acid

Review
In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004.
[updated ].

Excerpt

Optical fluorescence imaging is increasingly used to monitor biological functions of specific targets in small animals (1-4). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–650 nm) are used. Near-infrared (NIR) fluorescence (650–1,000 nm) detection avoids the natural background fluorescence interference of biomolecules, providing a high contrast between target and background tissues in small animals. NIR fluorophores have a wider dynamic range and minimal background fluorescence as a result of reduced scattering compared with visible fluorescence detection. NIR fluorophores also have high sensitivity, attributable to low background fluorescence, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is a noninvasive alternative to radionuclide imaging in small animals (4, 5).

Prostate-specific membrane antigen (PSMA) is a cell-surface glycoprotein with a molecular weight of ~100 kDa. It is a unique, type II, transmembrane-bound glycoprotein that is overexpressed on prostate tumor cells and in the neovasculature of most solid prostate tumors, but not in the vasculature of normal tissues (6, 7). PSMA has also been detected in other tissues such as the kidneys, the proximal small intestine, and the salivary glands (7). PSMA was found to have N-acetyl α-linked acidic dipeptidase (NAALADase) or glutamate carboxypeptidase II activity (8). PSMA may play an important role in the progression of prostate cancer and glutamatergic neurotransmission, as well as in the absorption of folate (9). In the central nervous system, PSMA metabolizes N-acetyl-aspartyl-glutamate, and in the proximal small intestine it removes γ-linked glutamates from poly-γ-glutamate folate and folate hydrolase (7). PSMA can be used as a marker for the detection of metastatic cancers with imaging agents. Although a commercially available monoclonal antibody (111In-labeled Capromomab pendetide (111In-CYT-356)) is in clinical use for the detection of prostate cancer, the results obtained with this antibody are not entirely reliable (10). In addition, this IgG antibody has limited access to tumors and also may produce low signal/noise ratios because the target is the intracellular domain of PSMA (11, 12). IRDye800CW-(3S,7S)-26-Amino-5,13,20-trioxo-4,6,12,21-tetraazahexacosane-1,3,7,22-tetracarboxylic acid (YC-27, also known as 800CW-3) is a small molecule inhibitor of NAALADase (13). YC-27 was able to visualize PSMA-positive tumors in nude mice, but accumulation of signal was high in the kidney. Chen et al. (14) evaluated a series of dye-3 conjugates with Cy5.5, IGC, IRDye800RS, and Cy7 in nude mice bearing human PSMA-positive xenografts. Injected Cy7-3 exhibited good tumor accumulation with lower liver and kidney accumulation than YC-27.

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