Near infrared planar tumor imaging and quantification using nanosized Alexa 750-labeled phospholipid micelles.

A novel highly biocompatible near infrared nanosized contrast agent was developed and used for rapid tumor detection and quantification using planar optical imaging and analysis. With this in mind, the near infrared fluorescent dye Alexa 750 was covalently attached to polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate, and double labeled (with Alexa and rhodamine) PEG-PE micelles were injected into mice and observed using planar optical imaging. Pixel intensity data from the tumor site were normalized versus the autofluorescence of the animal at the same time point and normalized as signal to noise over the scattered light from the various tissues of the mice. The detected signal from the tumor was higher than the background noise allowing for rapid detection of the tumor. The tumor was clearly visible within one hour. Some signal was also detected from the abdomen of the mice. As determined by microscopy analysis, other organs of accumulation were the liver and kidney, which corresponded well to the data from the whole body imaging animal studies.

Quantum dots encapsulated in phospholipid micelles for imaging and quantification of tumors in the near-infrared region.

Near-infrared (NIR) whole-body imaging is a powerful noninvasive method for the visualization of complex biological phenomena such as tumor and tumor vasculature and for whole-body studies. In this study we introduced a new NIR contrast agent in poly(ethylene glycol)-phospholipid micelle-encapsulated quantum dots (QD-Ms). QD-Ms maximally accumulated in the tumor area within 1 hour as compared to 4 hours for the commercially available PEGylated quantum dots (QD-PEGs) and allowed for the visualization of both tumor and internal organs. QD-Ms showed a signal-to-noise ratio of 15 that allowed the quantification of the micelles' biodistribution using image analysis. The signal obtained with the QD-Ms was higher than with the commercial formulation at half the QD dose. Overall, the QD-Ms seem to be a powerful and rapidly acting nanosized imaging agent that allows for effective visualization of tumors using NIR imaging.

Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo.

This study aimed to investigate the monoclonal antibody (mAb) 2C5 with nucleosome-restricted specificity for its ability to specifically recognize human brain tumor cells and to serve as a specific ligand for liposome targeting to brain tumor cells in vitro and in vivo. The affinity of mAb 2C5 towards brain tumor cells was tested by flow cytometry. The interaction of 2C5-immunoliposomes (ILS) with brain tumor cells in vitro was studied by fluorescence microscopy. For in vivo accumulation studies, (111)In-ILS were administered i.v. into mice bearing subcutaneously grown brain tumor. mAb 2C5 was found to be reactive against several tested brain tumor cell lines. mAb 2C5 and 2C5-ILS demonstrated enhanced cell-surface binding with CCF-STTG1,U-87 MG and LN-18 cells in vitro. 2C5-ILS displayed significantly better accumulation in the subcutaneously grown brain tumor than non-specific control IgG-ILS. mAb 2C5 specifically recognizes brain tumor cells and can serve as a ligand to target drug carriers such as liposomes to brain tumor cells in vivo.