Human transferrin receptor gene as a marker gene for MR imaging.
OBJECTIVE
To quantitate and characterize the expression of an engineered human transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR) imaging.


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.


CONCLUSIONS
ETR+ tumors internalize the MR imaging probe through the action of transferrin receptor in amounts that can be detected with MR imaging.
Moore
A
A
Center 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
Josephson
L
L
Bhorade
R M
RM
Basilion
J P
JP
Weissleder
R
R
D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000493:pharmacokinetics; D052203:Ferrosoferric Oxide; D005819:Genetic Markers; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D010087:Oxides / Q000493:pharmacokinetics; D015202:Protein Engineering; D051381:Rats; D011990:Receptors, Transferrin / Q000032:analysis* / Q000235:genetics*
D003287:Contrast Media; D005819:Genetic Markers; D010087:Oxides; D011990:Receptors, Transferrin; D007501:Iron; D052203:Ferrosoferric Oxide