Arginine-glycine-aspartic acid peptide-labeled quantum dot 705

Excerpt

Arginine-glycine-aspartic acid peptide-labeled quantum dot 705 (QD705-RGD) is an integrin-targeted molecular imaging agent developed for near-infrared (NIR) optical imaging of tumor vasculature (1). QD705 has an emission maximum at 705 nm.

Cellular survival, invasion, and migration control embryonic development, angiogenesis, tumor metastasis, and other physiologic processes. These processes are governed at both the extracellular and intracellular levels by several factors (2, 3). Among the molecules that regulate angiogenesis are integrins, a superfamily of cell adhesion proteins that form heterodimeric receptors for extracellular matrix (ECM) molecules (4, 5).These transmembrane glycoproteins consist of two noncovalently associated subunits, α and β (18 α- and 8 β-subunits in mammals), which are assembled into at least 24 α/β pairs. Some integrins recognize a single ECM protein ligand, whereas some can bind several ligands. Several integrins, such as integrin α_vβ₃, have affinity for the arginine-glycine-aspartic acid (RGD) tripeptide motif, which is found in many ECM proteins. Integrin α_vβ₃ receptor expression on endothelial cells is stimulated by angiogenic factors and environments. The integrin α_vβ₃ receptor is generally not found in normal tissue but is strongly expressed in vessels with increased angiogenesis, such as tumor vasculature. It is significantly up-regulated in certain types of tumor cells and in almost all tumor vasculature. Increased levels of integrin α_vβ₃ expression are closely associated with increased cell invasion and metastasis. Molecular imaging probes carrying the RGD motif that binds to the integrin α_vβ₃ can be used to image tumor vasculature and evaluate angiogenic response to tumor therapy (1, 6).

Optical imaging is an imaging method that utilizes light photons emitted from bioluminescence and fluorescence probes. Fluorescence imaging in the visible light range of 395-600 nm can penetrate only to a depth of 1-2 cm and has significant background signal because of tissue autofluorescence. NIR (700-900 nm) fluorescence imaging has the advantages of relatively higher tissue penetration and lower autofluorescence from non-target tissue (6). Quantum dots (QDs) are colloidal semiconductor nanocrystals with very high levels of brightness and photostability, high molar extinction coefficients, and broad absorption with narrow and symmetric photoluminescence spectra spanning the ultraviolet to NIR (7, 8). Their fluorescent emission can be size-tuned as a function of core size. The best QD fluorophores are mostly made of cadmium selenide (CdSe) cores overcoated with a layer of ZnS (9). The potential toxicity of QDs is not well established. Not all QDs are alike, and their toxicity appears to depend on multiple physicochemical factors (10). Studies have shown a concentration-dependent in vitro cytotoxicity of CdSe QDs under certain conditions, and this toxicity appears to be significantly reduced by coating (11-13). The surfaces of QDs can be modified to be water soluble and biocompatible, and QDs can be attached to targeting molecules such as antibodies and peptides. Cai et al. (1) developed the first RGD peptide-labeled QDs for imaging of integrin α_vβ₃-positive tumor vasculature.