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 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.
Zhang
Clare Y
CY
Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Lu
Jing
J
Tsourkas
Andrew
A
D015703:Antigens, CD / Q000096:biosynthesis; D002614:Chelating Agents / Q000494:pharmacology*; D003287:Contrast Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D020014:K562 Cells; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D008280:Magnetics; D053768:Metal Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism; D011990:Receptors, Transferrin / Q000096:biosynthesis*
D015703:Antigens, CD; C068126:CD71 antigen; D002614:Chelating Agents; D003287:Contrast Media; D005290:Ferric Compounds; D011990:Receptors, Transferrin; C000499:ferric oxide; D007501:Iron