Mono-dispersed high magnetic resonance sensitive magnetite nanocluster probe for detection of nascent tumors by magnetic resonance molecular imaging

Sensitive molecular imaging and detection of tumors or their supporting neovascularity require high-avidity, target-specific probes, which produce robust signal amplification compatible with a sensitive high-resolution imaging modality. In this context, we fabricated a high magnetic resonance (MR)-sensitive magnetite nanocluster (MNC) probe specific for tumor angiogenesis by assembly of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with (Mal) mPEG-PLA copolymer into cluster and subsequent encoding c(RGDyC) peptide on the cluster (RGD-MNC) for detection of nascent tumors. We found that RGD-MNC is highly sensitive (r(2) = 464.94 s(-1)mM(-1)) and specific for alpha v beta 3-positive cells. Both nascent (35 +/- 6.6mm(3)) and large tumors (256 +/- 22.3mm(3)) can be registered by RGD-MNC and detected by MR imaging (MRI), with the nascent tumors demonstrating more pronounced MR contrast. Immunohistochemical studies revealed that MR signal decrease was closely correlated with histological characteristics of tumors (microvessel density and alpha v beta 3 expression levels) at different growth stages. From the Clinical Editor: The authors demonstrate a method to image neovascularization in the context of tumors in an animal model utilizing functionalized SPIO particles. Although currently no SPIO or USPIO-based MRI contrast dye is approved for human use, in vivo cancer research projects may utilize this method in the near future, and hopefully similar applications will be available for human imaging as well. (C) 2012 Elsevier Inc. All rights reserved.