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Molecular MR imaging of melanoma angiogenesis with α ν β 3 ‐targeted paramagnetic nanoparticles
Author(s) -
Schmieder Anne H.,
Winter Patrick M.,
Caruthers Shelton D.,
Harris Thomas D.,
Williams Todd A.,
Allen John S.,
Lacy Elizabeth K.,
Zhang Huiying,
Scott Michael J.,
Hu Grace,
Robertson J. David,
Wickline Samuel A.,
Lanza Gregory M.
Publication year - 2005
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.20391
Subject(s) - in vivo , melanoma , angiogenesis , cancer research , chemistry , integrin , neovascularization , paramagnetism , ex vivo , vitronectin , alpha (finance) , molecular imaging , pathology , medicine , in vitro , microbiology and biotechnology , cell , biology , biochemistry , physics , construct validity , nursing , quantum mechanics , patient satisfaction
Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether α ν β 3 ‐targeted paramagnetic nanoparticles can detect and characterize sparse α ν β integrin expression on neovasculature induced by nascent melanoma xenografts (∼30 mm 3 ) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with α v β 3 ‐integrin‐targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or α v β 3 ‐targeted‐nonparamagnetic nanoparticles 2 hr before they were injected with α v β 3 ‐integrin‐targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received α ν β 3 ‐targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group ( P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of α ν β 3 ‐expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin‐coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting. Magn Reson Med 53:621–627, 2005. © 2005 Wiley‐Liss, Inc.