Micro-CT molecular imaging of tumor angiogenesis using a magnetite nano-cluster probe.

Abstract

Due to its high resolution, micro-CT is desirable for molecular imaging of tumor angiogenesis. However, the sensitivity of micro-CT to contrast agents is relatively low. Therefore, the purpose of this study is to develop high micro-CT sensitive molecular imaging probes for direct visualization and dynamic monitoring of tumor angiogenesis. To this end, Arg-Gly-Asp (RGD) peptides conjugated magnetite nano clusters (RGD-MNCs) were developed by assembling individual magnetite nano particles into clusters with amphiphilic (maleimide) methoxypoly(ethylene glycol)-b-poly(lactic acid) ((Mal)mPEG-PLA) copolymer and subsequently encoding RGD peptides onto the clusters for specific targeting alpha(v)beta3 integrin. The hydrodynamic size of RGD-MNCs was about 85 nm. To test its specificity, alpha(v)beta3 positive cells (H1299) were incubated with magnetite nano clusters (MNCs), RGD-MNCs or RGD-MNCs competition with free RGD peptides. Prussian Blue staining and inductively coupled plasma optical emission spectrometer (ICP-OES) measurements indicated that the cell uptake of RGD-MNCs was significantly more than that of MNCs, which could be inhibited by free RGD peptides. For detection of tumor angiogenesis, mice bearing H1299 tumors were injected intravenously with RGD-MNCs at the dose of 400 micro mol Fe/kg. Tumor angiogenic hot spots as well as individual angiogenic vessels could be clearly manifested by micro-CT imaging 12 h post injection, which was dynamically monitored with the extension of probe circulation time. Subsequent histological studies of tumor tissues verified that RGD-MNCs registered tumor angiogenic vessels. Our study demonstrated that RGD-MNC probes fabricated in this study could be used to effectively target alpha(v)beta3 integrin. Using high resolution micro-CT in combination with the probes, tumor angiogenesis could be studied dynamically.

• Authors: Ping Liu, Jing Li, Chunfu Zhang, Lisa X Xu
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 9 Issue 6 Pg. 1041-9 (Jun 2013) ISSN: 1550-7033 [Print] United States
• PMID: 23858968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contrast Media
• Magnetite Nanoparticles

Topics

• Animals
• Cell Line, Tumor
• Contrast Media (chemical synthesis)
• Humans
• Image Enhancement (methods)
• Lung Neoplasms (complications, diagnostic imaging)
• Magnetite Nanoparticles (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neovascularization, Pathologic (complications, diagnostic imaging)
• Particle Size
• Tomography, X-Ray Computed (methods)