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Human transferrin receptor gene as a marker gene for MR imaging
A Moore1, L Josephson, R M Bhorade
1Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Bldg 149, 13th St, Rm 5419, Charlestown, MA 02129, USA. amoore@helix.mgh.harvard.edu
Purpose:
To quantitate and characterize the expression of an engineered human transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR) imaging.
Materials And Methods:
Rat gliosarcoma 9L cells stably expressing ETR (ETR+) were used, with nontransfected (ETR-) cells serving as controls. A conjugate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles was synthesized to probe for the activity of ETR. Accumulation of Tf-MION was examined by using cell internalization in culture and MR (n = 6) and nuclear (n = 4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite flanks. Autoradiographic and histopathologic results were correlated with MR findings.
Results:
Tf-MION was internalized by ETR+ cells at 37 degrees C but not at 4 degrees C. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ETR colocalized in small vesicle-like structures in the cytoplasm. Both findings were consistent with accumulation by the receptor-mediated endocytosis mechanism of ETR. Compared with ETR- tumors, ETR+ tumors accumulated more Tf-MION and had higher signal intensity on T1-weighted MR images and lower signal intensity on T2-weighted images. Autoradiographic findings showed a spatial correlation between MR signal intensity and TF-MION accumulation.
Conclusion:
ETR+ tumors internalize the MR imaging probe through the action of transferrin receptor in amounts that can be detected with MR imaging.