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Near-infrared (NIR) fluorescence used to obtain biological functions of specific targets

Near-infrared (NIR) fluorescence used to obtain biological functions of specific targets

Kam Leung

PMID: 20641862

Abstract:

Optical fluorescence imaging is increasingly used to obtain biological functions of specific targets (1, 2). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350-700 nm) are used. Near-infrared (NIR) fluorescence (700-1,000 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues. NIR fluorophores have wider dynamic range and minimal background as a result of reduced scattering compared with visible fluorescence detection. They also have high sensitivity, resulting from low infrared background, 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 becoming a non-invasive alternative to radionuclide imaging in vitro and in rodents.
Integrins are a family of cell surface heterodimeric glycoproteins that mediate diverse biological events involving cell-cell and cell-matrix interactions (3). They consist of an α and a β subunit. They are important for cell adhesion and signal transduction. The α4β1 integrin plays an important role in hematopoiesis of lymphocytes. On the other hand, it affects tumor growth, tumor invasiveness, and metastasis (4). The α4β1 integrin is strongly expressed on lymphoid tumor cells (5). N-[[4-[[[(2-ethylphenyl)amino]carbonyl]amino]phenyl]acetyl]-N(epsilon)-6-[(2E)-1-oxo-3-(3-pyridinyl-2-propenyl)]-L-lysyl-L-2-aminohexanedioyl-(1-amino-1-cyclohexane)carboxamide (LLP2A) was identified as a peptidomimetic ligand to bind to α4β1 integrin on human Jurkat T-lymphoid leukemia cells using "one-bead one compound" combinatorial libraries (6, 7). A benzothiazole analog, (R)-5-(R)-[2-(2-[4-(benzothiazol-2-ylamino)-phenyl]acetylamino)-6-(E)-(3-pyridin-3-yl-acryloylamino)hexanoylamino]-5-(1-carbamoylcyclo-hexylcarbamoyl)pentanoic acid (LLP2A-6), has been conjugated with Cy5.5 (Cy5.5-LLP2A-6) to study in vivo biodistribution of the tracer in tumor-bearing mice (8). Cy5.5 is a NIR fluorescence dye with absorbance maximum at 675 nm and emission maximum at 694 nm with a high extinction coefficient of 250,000 M-1cm-1. Cy5.5-LLP2A-6 has been found to have high accumulation in α4β1-positive lymphoid tumor cells in nude mice.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP162411316	NIR 5e		162411-31-6	Price

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