High throughput magnetic resonance imaging for evaluating targeted nanoparticle probes.
The ability to image specific molecular targets in vivo would have significant impact in allowing earlier disease detection and in tailoring molecular therapies. One of the rate-limiting steps in the development of novel compounds as reporter probes has been the lack of cell-based, biologically relevant, high throughput screening methods. Here we describe the development and validation of magnetic resonance imaging (MRI) as a technique to rapidly screen compounds that are potential MR reporter agents for their interaction with specific cellular targets. We show that MR imaging can (1) evaluate thousands of samples simultaneously and rapidly, (2) provide exceedingly accurate measurements, and (3) provide receptor binding/internalization data as validated by radioactive assays. The technique allows the screening of libraries of peptide-nanoparticle conjugates against target cells and the identification of conjugates that may be subsequently used as reporter agents in vivo. The technology should greatly accelerate the development of target-specific or cell-specific MR contrast agents.
Högemann
Dagmar
D
Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Ntziachristos
Vasilis
V
Josephson
Lee
L
Weissleder
Ralph
R
D002460:Cell Line; D003627:Data Interpretation, Statistical; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008863:Microspheres; D036103:Nanotechnology; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results
D019151:Peptide Library; D010455:Peptides; D011990:Receptors, Transferrin