Human transferrin receptor gene as a marker gene for MR imaging

PURPOSE: To quantitate and characterize the expression of an engineered hum an 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 conjug ate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles w as synthesized to probe for the activity of ETR. Accumulation of Tf-MION wa s examined by using cell internalization in culture and MR (n = 6) and nucl ear (n = 4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite flanks. Autoradiographic and histopathologic results were cor related with MR findings. RESULTS: Tf-MION was internalized by ETR+ cells at 37 degreesC but not at 4 degreesC. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ET R colocalized in small vesicle-like structures in the cytoplasm. Both findi ngs were consistent with accumulation by the receptor-mediated endocytosis mechanism of ETR. Compared with ETR- tumors, ETR+ tumors accumulated more T f-MION and had higher signal intensity on T1-weighted MR images and lower s ignal intensity on T2-weighted images. Autoradiographic findings showed a s patial 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.