Iron chelator-based amplification strategy for improved targeting of transferrin receptor with SPIO

A major obstacle faced by magnetic resonance (MR) as a platform for molecular imaging is the low sensitivity for detecting receptor-targeted MR contrast agents. The versatility of MR imaging, however, could be improved if there existed a strategy to upregulate the receptor of interest prior to admin...

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Bibliographic Details
Published in:Cancer biology & therapy 2008-06, Vol.7 (6), p.889-895
Main Authors: Zhang, Clare Y., Lu, Jing, Tsourkas, Andrew
Format: Article
Language:English
Subjects:
Antigens, CD - biosynthesis
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Chelating Agents - pharmacology
Contrast Media - pharmacology
Cycle
Dose-Response Relationship, Drug
Ferric Compounds - chemistry
Gene Expression Regulation
Humans
Iron - chemistry
Iron - pharmacology
K562 Cells
Landes
Magnetic Resonance Imaging - instrumentation
Magnetic Resonance Imaging - methods
Magnetics
Metal Nanoparticles - chemistry
Neoplasms - metabolism
Organogenesis
Proteins
Receptors, Transferrin - biosynthesis
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Summary:A major obstacle faced by magnetic resonance (MR) as a platform for molecular imaging is the low sensitivity for detecting receptor-targeted MR contrast agents. The versatility of MR imaging, however, could be improved if there existed a strategy to upregulate the receptor of interest prior to administration of the targeted contrast agent. Here, we describe an amplification strategy that uses iron chelators to upregulate the transferrin receptor (TfR) prior to administration of TfR-targeted superparamagnetic iron oxide nanoparticles (SPIO). When K562 human leukemic cells were incubated with the iron chelator desferrioxamine (DFO), followed by administration of anti-TfR SPIO, there was a 57% improvement in the T2 relaxation time compared with cells not treated with DFO and an 82% improvement compared with cells not targeted with SPIO. The effects of incubation time, temperature, SPIO concentration, and targeting molecule on contrast enhancement were also examined. The results reported here suggest that iron chelators have the potential to significantly improve the sensitivity of TfR-mediated cancer detection, providing a new paradigm for MR signal amplification.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.7.6.5893